A human monoclonal for RSV prophylaxis

DESCRIPTION provided by applicant Respiratory syncytial virus RSV is the leading cause of lower respiratory tract illness in infants and young children worldwide In premature neonates RSV infection results in high levels of morbidity and mortality In the United States alone there are more than hospitalizations and deaths per year attributable to RSV The only prophylaxis for RSV is Synagis palivizumab MedImmune a humanized murine monoclonal antibody mAb that targets the RSV glycoprotein F and has been shown to reduce the rate of RSV associated hospitalization by In order to prevent a single hospitalization it has been estimated that neonates need to be treated with Synagis Since a single course of Synagis treatment can cost in excess of $ per infant the resulting cost effectiveness analysis is not favorable Moreover due to this high cost Synagis is inaccessible to children in developing nations and is unavailable in of the most populous countries more than half the worldandapos s population does not have access to this life saving treatment Further reports of Synagis resistant RSV strains emphasize the need for additional anti RSV products against different epitopes Aridis Pharmaceutical has screened RSV infected patients and identified a naturally occurring human monoclonal IgG andapos AR andapos with higher potency than Synagis that neutralizes Synagis resistant strains The aim of this proposal is to further the development of AR to address the above mentioned limitations To this end Aridis Pharmaceutical has teamed with Mapp Biopharmaceutical to jointly develop a mAb product AR with the following characteristics Fully human Synagis is a humanized mouse mAb Higher affinity and in vitro neutralization potency than Synagis Binds a different epitope than Synagis and neutralizes a Synagis resistant strain Increased serum half life so injections can be administered less frequently than the monthly dosing required for Synagis Lower cost due to manufacture in Nicotiana benthamiana using the highly scalable Rapid Antibody Manufacturing Platform RAMP In Specific Aim we will produce AR in both the RAMP system and in CHO cells AR will be expressed in Nicotiana benthamiana and CHO cells as both the unmodified sequence and as sequences introducing amino acid mutations that result in increased affinity for FcRn resulting in extended serum half life In Specific Aim the mAbs will be compared in vitro Measurements will assess affinity for glycoprotein F and neutralization activity of the mAbs against a large panel of RSV isolates including Synagis resistant strains In Specific Aim the mAbs will be compared in vivo The cotton rat model will be used to compare the efficacy of the mAb variants to select a lead mAb for continued product development in a subsequent Phase SBIR proposal PUBLIC HEALTH RELEVANCE The efforts in this proposal will help in the development of a drug product for preventing infection with Respiratory Syncytial Virus a highly infectious virus that causes significant morbidity and mortality in premature infants and immunocompromised patients