Novel Recombinant High-Affinity, Long- and Dual-Acting Equine CG Analogs for Improved and More EthicalReproduction in Pigs and Cattle

The current proposal of the PI’s second veterinary product, the first more potent and long acting recombinant equine chorionic gonadotropin (reCG) agonist for improved and, for the first time, totally ethical reproduction in pigs and cattle by acceleration to the times of estrus is estimated to be $ 200 M + annual market, a potential veterinary product “blockbuster”! The currently used animal product, pregnant mare serum gonadotropin (PMSG) obtained by increasingly recognized inhumane bleeding of noble pregnant mares is highly controversial, has raised increasing concerns among animal rights activists, regulatory and political bodies which have already or soon plan to ban the sale of PMSG. Our previous Phase 1 eCG SBIR achieved a remarkable impact score of 25 and was funded by NICHD in its first submission. The most remarkable aspects of this current Phase 2 SBIR submission is that, first, we provide compelling data that we have not only achieved but have greatly exceeded all aims of our Phase 1 eCG analog SBIR proposal. Secondly and remarkably, we have already established an extraordinarily advantageous commercialization agreement in Phase 1 with Merck Animal Health, the manufacturer of the leading current PMSG product which vitally wishes to replace its natural eCG with this greatly improved recombinant analog. Our aims are: YEAR 1 Aim 1: Improve expression, glycosylation and a major commercial scale up of its bioreactor production and purification methods: A. State of the art permeable beads with adherent CHO cells in suspension; B. Larger fibrous bed bioreactor as developed in Phase 1; C. Possible adaptation of adherent CHO cells to direct growth in suspension culture; Aim 2: Extensive PK studies in rodents to model optimized dose ranging amount and injection number of in vivo bioassays. YEAR 2 Aim 1: Development of CHO Cell Master Cell Bank under GMP conditions of either adherent or suspension cells suitable for transfer to a Merck Animal Health Commercial Bioreactor Facility; Aim 2: Testing of multiple commercial uses of the eCG in both pigs and cows in parallel with Merck Animal Health under GLP conditions suitable to submit an INAD to FDA-CVM and begin regulatory discussions for Fast Track Approval for human and animal safety and ethical treatment of horses: A. Synchronization and acceleration to estrus in gilts and sows; B. Synchronization and acceleration to estrus in heifers and cows; C. Superovulation of cattle; Aim 3: Testing for presumed immunogenicity of the human CG component within Merck’s PG 600: A. Serum immunogenicity studies to hCG and eCG on single and repeated use; B. Possible attenuation of clinical response in repeated use. In view of the PI’s remarkable success in commercializing its very first veterinary bovine FSH analog product with world leader animal pharma Zoetis and now, secondly, for its eCG analog by number 3 animal pharma, Merck Animal Health, we believe this Phase 2 proposal strongly merits expedited approval.The current proposal of the PI’s first recombinant, much more potent and long-acting equine (horse) chorionic gonadotropin (eCG) agonist for improved and, for the first time, totally ethical reproduction in pigs and cattle is estimated to be a very large $ 200 M + annual market, a potential veterinary product “blockbuster”! The goal of this project is to develop and evaluate new recombinant equine chorionic gonadotropin (eCG) analogs as replacement for pregnant mare’s serum gonadotropin (PMSG). The use of PMSG obtained by increasingly recognized inhumane bleeding of noble pregnant mares is highly controversial has raised increasing concerns among animal rights groups, regulatory and political bodies which have already or soon plan to ban the sale of PMSG throughout the world.