AZIRIDINYL GROUPS CONTAINING POLYAMINES AS ANTI-PATHOGEN DEVICE FOR BLOOD PRODUCTS INTENDED FOR TRANSFUSION

DESCRIPTION provided by applicant It is generally accepted that the current risk of transfusion transmitted infections is lower than ever In order to maintain the high level safety o the blood supply besides donor deferral system up to a dozen blood pathogen tests are conducted with each donated blood unit However despite using all those sophisticated tests the risk of transfusion transmitted infections still persists because the concentration of the pathogen at andquot window periodandquot can be below the limit of detection known but currently not tested pathogens can be present and due to emerging and yet to be identified infectious agents Therefore the high efficacy anti pathogen compound APC that enables the inactivation of all blood borne pathogens BBP represents an unmet medical need Depending on medical conditions a leukodepleted blood plasma platelets or red blood cell concentrates RBCC are transfused Due to the absence of nuclei in platelets and RBC targeting and inactivating BBP genomes remains one of the most advantageous approaches examined up to date Large varieties of compounds have been tested but none of them was fully materialized into an effective anti pathogen device APD for blood sterilization We at ZATA consider the development of novel APCs that selectively aggregate with and damage nucleic acid NA molecules On the molecular level the structures of ZATAandapos s APCs will consist of linear and branched polyamines PA with covalently attached one to three aziridinyl groups AzG at the termini Distances between positive charges in the backbones of these PA coincide with the distances between negative charges in the backbones of NA Such spacing will enable the simultaneous ion paring SIP of each positive charge of APC with the corresponding negative charge of DNA RNA resulting in the formation of strong aggregates The aggregation in turn will selectively bring AzG of APC in close proximity to the nucleophilic centers of NA and fully inactivate them via alkylation of those centers These unique properties of our APC will enable high efficacy of inactivation at low M concentration of the compound Removal of residual APC and product of its degradation from the post treatment blood product by using of disposable cartridge integrated in a closed APC delivery system is a part of the treatment procedure that qualifies our APC as devices i e not therapeutic compounds There are three main milestones we anticipate to achieve during Phase I of the project I Development of the methodology that will enable the synthesis of a panel of APC based on preliminary data and their controls by adopting well established chemistry as described in research plan II Testing these compounds against representative pathogens to select optimal APD III Development of a simple SINGLE step treatment procedure and biochemical evaluation of the quality of treated blood products Feasibility of the proposed technology is supported by preliminary data At the end of Phase I the best APC candidate will be selected for the Phase II study and validated against major types of pathogens that can be present in blood K clearance filing for optimal ZAPC is considered Broad provisional patent application describing ZATAandapos s APC related IP has been filed PUBLIC HEALTH RELEVANCE Linear and branched polyamines with covalently attached aziridinyl groups at the termini as anti pathogen devices in blood products intended for transfusion are proposed