Glycobac, LLC — Department of Health and Human Services SBIR Phase I: 300

Description

Abstract The global market for `biologicsandaposwhich are new generation drugs produced using genetically engineered biological systemsis projected to reach $billion byOne system currently being used to manufacture biologics is the baculovirus insect cell systemBICSThe BICS offers certain advantages over more widely used mammalian cell systemsincluding its rapid adaptability for manufacturing different productsuse of a single qualified master cell bank for all productsabsence of endogenous retrovirusesand superior ability to produce multiprotein complexesIt also presents an alternative for products that are poorly produced in mammalian cell systems and enhances manufacturing capacityHoweverthe BICS cannot be used to manufacture glycoprotein biologicsthe most common typebecause it cannot produce the human type carbohydrate side chainsor `N glycansandaposrequired for their clinical efficacyGlycoBac has shown we can solve this problem using our patented technology to produce insect cell derivatives that can synthesize human type N glycansSo farour `glycoengineeringandaposefforts have focused on cell lines derived from SfrugiperdaSfbecause they are most commonly used in the BICSHoweverTniTncell lines are also used and have the capacity for higher productivityConsidering thisglycoengineered Tn cell lines would be highly attractive to glycoprotein biologics manufacturersUnfortunatelyglycoengineering currently available Tn lines would be useless because these lines are contaminated with a virusand produce immunogenic N glycansThese problems have thwarted GlycoBacandapos s opportunity to leverage our technology and glycoengineer Tn cellswhich would double our product catalogThuswe isolated a newpatent pending Tn line that has no viral contaminants and produces no immunogenic glycansWe now propose to use this line to demonstrate the feasibility of Tn glycoengineeringFirstwe will knockout the endogenous fused lobesfdlgenewhich antagonizes human type N glycan elongationWe will do this using our newpatent pendinglepidopteran insect specific CRISPR Castoolswhich will provide a competitive advantageSecondwe will knock in heterologous genes required for human type N glycan synthesis using our established technologywhich also will provide a competitive advantageand characterize the productThe results will reveal if it is feasible to glycoengineer Tn cells and isolate derivatives that can produce glycoproteins with human type N glycansA successful outcome will set the stage for Phase IIin which we would produce a full suite of glycoengineered Tn derivatives designed to produce recombinant glycoproteins with various clinically relevant N glycan structuresWe would extensively characterize these lines and document their safety and efficacyThese new glycoengineered insect cell lines would grow GlycoBacandapos s businesseffectively doubling our catalogas noted aboveThis would enhance global manufacturing capacity for glycoprotein biologicswhich have the biggest impact on human health andthereforeenhance the biotechnology sectorsandaposefforts to improve human health Narrative The global market for `biologicsandaposwhich are new generation drugs produced using genetically engineered biological systemsis projected to reach $billion byThe baculovirus insect cell system is currently being used to manufacture biologicsbut this system has a key technical limitation that restricts its utility to a small segment of the overall biologics manufacturing marketThis Phase I SBIR project will assess the feasibility of using GlycoBacandapos s patented technology to overcome this restriction by creating a new suite of insect cell lines fornd generation baculovirus insect cell systems that can be used to manufacture a broader selection of biologics and increase our share of this large market