Osteoporosis is a staggering burden to those affected by the disease and to society. In the U.S. today, 10 million individuals are estimated to already have the disease and almost 34 million more are estimated to have low bone mass, placing them at increased risk for osteoporosis. Efforts to find highly effective therapies that focus on inhibiting disease progression and prevention are of great value. Vaccinex Inc. is recognized for its use of vaccinia virus as an expression tool. Vaccinex scientists have created representative cDNA libraries in our proprietary vaccinia expression system for a variety of purposes including antigen discovery and functional gene selection. Recently this expression system was modified to allow for the expression and production of fully human, bivalent monoclonal antibodies from separate heavy and light chain variable-gene libraries. This technology has afforded us the opportunity to effectively target proteins that would otherwise be immunogenic in a mouse antibody platform. Additionally, our expression and screening takes place in mammalian cells and therefore benefits from proper folding and posttranslational processing ensuring that selected antibodies will retain specificity and affinity when used in mammalian models and eventually the clinic. In this application, we propose to use the Vaccinex Antibody Selection platform to isolate a fully human, monoclonal antibody against mouse Noggin capable of neutralizing the activity of this protein. Published data support an inhibitory role for Noggin in bone development and maintenance. We hypothesize that by inhibiting Noggin we will either maintain or increase total bone density by enhancing the activity of endogenous or therapeutically applied Bone Morphogenetic Proteins (BMP's). Monoclonal antibody therapeutics are increasingly becoming important clinical tools to combat cancer and inflammation. Relative to other therapies, antibodies represent the combined benefits of specificity, effectiveness, purity, and unlimited reproducibility. An anti-osteoporotic antibody therapy would be of enormous value to society. ? ? ?