SAIFER, MARK G.P.,MARTINEZ, ALEXA L.,WILLIAMS, L. DAVID,SHERMAN, MERRY R.
申请号：
CA2511814
公开号：
CA2511814C
申请日:
2003.12.23
申请国别(地区):
CA
年份:
2015
代理人:
摘要：
Methods are provided for the synthesis of polymer conjugates of cytokines andreceptor-binding antagonists thereof, especially a non glycosylated interferon-beta, which conjugates retain unusually high biological potency. Preparationof polymer conjugates according to the methods of the present inventiondiminishes or avoids steric inhibition of receptor-ligand interactions thatcommonly results from the attachment of polymers to receptor-binding regionsof cytokines, as well as to agonistic and antagonistic analogs thereof. Theinvention also provides conjugates and compositions produced by such methods.The conjugates of the present invention retain a high level of biologicalpotency compared to those produced by traditional polymer coupling methodsthat are not targeted to avoid receptor-binding domains of cytokines. Inassays in vitro, the biological potency of the conjugates of non-glycosylatedinterferon-beta of the present invention is substantially higher than that ofunconjugated interferon-beta and is similar to that of interferon-beta-1a thatis glycosylated. The conjugates of the present invention also exhibit anextended half-life in vivo compared to the corresponding unconjugatedcytokine. The present invention also provides kits comprising such conjugatesand/or compositions, and methods of use of such conjugates and compositions ina variety of diagnostic, prophylactic, therapeutic and bioprocessingapplications, including treatment of multiple sclerosis.
