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Quantitation Pulmonary Delivery of Therapeutic Protein
Phone: (858) 455-6907
Phone: (858) 455-6907
Type: Nonprofit College or University
DESCRIPTION (provided by applicant): Arizeke Pharmaceuticals, Inc. is focused on the pulmonary delivery of protein therapeutics (including antibodies) to treat pulmonary disease. Arizeke's technology provides a unique ability to deliver large therapeutic proteins into the lung parenchyma and interstitium and into the lymphatic drainage system. Examples of indications that can be targeted by this technology include hereditary emphysema, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and cancers resident in the lungs. Therapeutics can also be delivered to the peripheral blood where they will also be beneficial in the treatment of cancer and other diseases. The initial target for our lead product (AZ-AAT) is hereditary emphysema. Arizeke has developed a lung delivery technology that uses polymeric immunoglobulin receptor (plgR) to delivery fusion proteins consisting of a plgR-binding ligand (single chain Fv, sFv) and a protein therapeutic. The sFv (APL9) originated from a library of human VH and VL regions and is expected to be nonimunnogenic. The chimeric proteins are formulated for inhalation as an aerosol and they are delivered by specific transcytosis across the epithelium to treat lung diseases. The technology has demonstrated its ability to transport large proteins to lung parenchyma and interstitial space. Direct access with large molecules to this compartment of the lung, which is the principal site of many disease processes, is unique among pharmaceutical therapeutics. plgR is abundantly distributed throughout the pulmonary tract as well as other mucosal membranes. The function of plgR is to move immunoglobulins (IgA dimers [MW 350,000] and IgM pentamers [MW 900,000]) from the basolateral side of the epithelial layer, through the epithelial cell and release them into the lumen (the apical side of the epithelial layer). plgR naturally cycles from the basolateral (interstitial) surface of epithelial cells to the apical (lumen) surface of epithelial cells. The basis of Arizeke's proprietary technology is the unexpected observation that plgR binding sFv (and its variants) binds to a specific epitope on plgR and is transported in the reverse direction, namely from the lumen to the interstitial space. The chimera is released into the lung interstitial space and will eventually enter lymph channels. Using confocal microscopy, we will quantitate the AZ-AAT transport path through the pulmonary system.
* Information listed above is at the time of submission. *