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 and therapeutic applications, including treatment of multiple sclerosis.L'invention concerne des procédés de synthèse de conjugués polymères de cytokines et d'antagonistes se liant aux récepteurs de celles-ci, notamment un interféron-bêta, non glycosylé, ces conjugués conservant une activité biologique exceptionnellement élevée. La préparation des conjugués polymères, selon les procédés de l'invention, permet de réduire ou d'éviter l'inhibition stérique des interactions récepteur-ligand généralement engendrée par la fixation de polymères aux régions de liaison des récepteurs des cytoki
