MUTANTS OF THYROID STIMULATING HORMONE AND METHODS BASED THEREON

摘要

The present invention is based upon the discovery that mutant alpha subunits and mutant beta subunits each comprising amino acid substitutions relative to the wild type can be produced and assembled to form a mutant TSH heterodimer or TSH analog that possesses higher bioactivity in vitro and longer half life in vivo. Accordingly, the present invention provides methods for using mutant TSH heterodimers, TSH analogs, fragments, and derivatives thereof for treating or preventing diseases of the thyroid, in particular thyroid cancer. The invention also relates to methods of diagnosis, prognosis and monitoring for thyroid-related functions. Pharmaceutical and diagnostic compositions, methods of using mutant TSH heterodimers and TSH analogs with utility for treatment and prevention of metabolic and reproductive diseases are also provided.