Methods are provided for the synthesis of
polymer conjugates of cytokines and
receptor-binding antagonists thereof, especially a non glycosylated
interferon-beta, which conjugates retain unusually high biological
potency. Preparation of
polymer conjugates according to the methods of the present invention diminishes or avoids steric inhibition of
receptor-ligand interactions that commonly results from the attachment of polymers to
receptor-binding regions of cytokines, as well as to agonistic and antagonistic analogs thereof. The invention also provides conjugates and compositions produced by such methods. The conjugates of the present invention retain a high level of biological
potency compared to those produced by traditional
polymer coupling methods that are not targeted to avoid receptor-binding domains of cytokines. In assays
in vitro, the biological
potency of the conjugates of non-glycosylated
interferon-beta of the present invention is substantially higher than that of unconjugated
interferon-beta and is similar to that of interferon-beta-1a that is glycosylated. The conjugates of the present invention also exhibit an extended half-life
in vivo compared to the corresponding unconjugated
cytokine. The present invention also provides kits comprising such conjugates and / or compositions, and methods of use of such conjugates and compositions in a variety of diagnostic, prophylactic, therapeutic and bioprocessing applications, including treatment of
multiple sclerosis.