Human monoclonal antibodies for prevention of S. aureus infections

DESCRIPTION provided by applicant Using mouse monoclonal antibodies mAbs raised against the mediators of quorum sensing QS the Auto Inducing Peptides AIPs researchers at The Scripps Research Institute TSRI have demonstrated that S aureus infections can be prevented in animal challenge models This approach known as quorum quenching QQ is unique in at least two significant ways first rather than eliminating bacteria associated with infection the QQ approach modulates the global virulence of the invading pathogens thus allowing the bacteria to be cleared by the hostandapos s immune system second the AIPs are not essential for the growth of the bacteria per se so the selective pressure for the generation of resistance should be greatly reduced Sorrento Therapeutics Inc STI has licensed QQ technology from TSRI STI will humanize anti AIP mouse mAbs and isolate a fully human anti AIP antibody from its proprietary antibody library then combine them into the product candidate STI a single tetraspecific antibody like molecule to prevent S aureus infections through QQ We here outline experiments for the development and validation of STI an IgG like molecule that would virtually eliminate morbidity and mortality when used in prophylactic settings In Phase I the murine anti AIP mAbs B and H will be humanized and characterized in vitro as well as in animal models In addition a human mAb against the remaining AIP not covered by the TSRI mAbs namely AIP will be identified from STIandapos s antibody library and also generated The anti AIP mAbs will be combined into a single IgG like molecule namely product candidate STI evaluated in vitro as well as in vivo and taken into STTR Phase II In Phase II STI will be produced in large scale for testing in additional animal models and preclinical development e g pharmacokinetic PK dynamic PD and toxicological analyses as well as dosing studies We will also generate a master cell bank and prepare initiate IND filling This immunotherapeutic approach of sequestering the mediators of bacterial virulence in order to prevent infection will provide a much needed alternative to traditional antibiotic based treatments to ameliorate S aureus infections including those resistant to antibiotics Despite the approval of numerous antibiotics over the past years bacterial disease remains a serious public health problem Many of the most harmful bacteria including Staphylococcus aureus develop resistance to approved antibiotics so called andquot superbugsandquot causing people with drug resistant infections to become seriously ill or die Sorrento Therapeutics Inc is working on the development of a new way to prevent and even treat bacterial disease in a manner that we believe will be much more effective than using current antibiotic therapy and that will be unaffected by existing resistances