Novel Recombinant High Affinity Long and Dual Acting Equine CG Analogs for Improved and More Ethical Reproduction in Pigs and Cattle

As their first application for veterinary health the two PI s have already remarkably employed their novel patented superagonist and neoglycosylation technology to develop the first recombinant much more potent and long acting bovine FSH antagonists for improved cattle reproduction and a potential $ Million annual market This work was supported by a previous phase SBIR from FDA CVM which proved vital in obtaining required data for an FDA NADA and ultimately for a large licensing andamp commercialization agreement with Zoetis the world s leading veterinary health company The current proposal of the first recombinant much more potent and long acting equine chorionic gonadotropin eCG agonists for improved and more ethical reproduction in pigs and cattle is estimated both by Trophogen and potential partnering veterinary pharma companies to be an even larger annual worldwide market of $ Million a potential veterinary blockbuster ! In view of the PI s remarkable success in developing and commercializing its first veterinary product with support of a phase SBIR from FDA and validation of its technology and the potential market value of its reproductive products by world leader Zoetis we hope that the current submission will receive expedited approval The goal of this Phase project is to develop and evaluate new recombinant eCG analogs as replacement for pregnant mare s serum gonadotropin PMSG and P G PMSG hCG The use of PMSG obtained by inhumane bleeding of pregnant mares between days and of gestation is highly controversial and an inhumane business of PMSG production raises increasing concerns of the public and animals rights group There are many limitations of current PMSG and related products including presence of horse serum contaminants in PMSG preparations potential infection with equine viruses and prions as well as immunological responses to highly heterogenous preparations produced in heterologous species horse or human There are no approved recombinant veterinary eCG products and the PIs were highly encouraged by increasing interest from major veterinary companies in their totally novel more potent and longer acting recombinant gonadotropins including new eCG analogs In this Phase we plan to Aim A Develop novel high affinity recombinant eCG superagonist analogs by minimal arginine site directed mutagenesis to produce a more potent and efficacious dual FSH LH CG activity molecule Aim B For selected eCG superagonists also engineer a novel minimal length amino acid insert containing one or two complex carbohydrate neoglycosylation sites to further increase half life and produce analogs without reducing increased superagonist potency efficacy Aim Optimize production and purification of these novel analogs using stable highly expressing Chinese hamster ovary CHO cell lines and low cost production methods in roller bottles Aim Select the best analog candidates and characterize them in vitro by previously validated eCG analog ELISA immunoassay SDS PAGE electrophoresis isoelectric focusing IEF gel analysis and robust in vitro FSH and LH CG bioassays Aim Select the final eCG analog using the most important parameter determining in vivo performance pharmacokinetic PK studies in mice Aim Establish CHO research cell bank RCB providing high expression of the lead optimally neoglycosylated eCG analog sufficient for more expensive bioreactor production and all extensive rodent pig and cattle studies in Phase Pregnant mare s serum gonadotropin PMSG eCG obtained from horse blood farms is the main ingredient of several veterinary products that are artificially inducing heat in weaned sows to achieve a faster and more controlled reproduction There are many limitations ethical concerns and risks associated with PMSG derived from serum of pregnant mares including possible contamination by a protein infectious agent which causes a fatal brain disease in humans after eating infected meat The design and development of the first synthetic DNA derived highly pure much more potent and long acting dual activity eCG analog which cannot contain any infectious agent offers not only prospects of largely improved safe and more ethical reproduction in pigs and cattle but also a unique potential for veterinary reproduction blockbuster with multiple applications in different species!