| 摘要 |
The present invention provides synthetic Type I interferon receptor polyp eptide agonists comprising consensus or hybrid Type I interferon receptor po lypeptide agonists, containing one or more native or non-native glycosylatio n sites. The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon recep tor polypeptide agonists, containing one or more native or non-native glycos ylation sites, as well as erythropoietin and darbepoetin alfa, each of which are linked to a penetrating peptide that facilitates translocation of a sub stance across a biological barrier as well as pharmaceutical compositions, i ncluding oral formulations, of the same. The present invention further provi des oral formulations of hyperglycosylated or protease-resistant, hyperglyco sylated polypeptide variants, which polypeptide variants lack at least one p rotease cleavage site found in a parent polypeptide, and thus exhibit increa sed protease resistance compared to the parent polypeptide, which polypeptid e variants further include (1) a carbohydrate moiety covalently linked to at least one non-native glycosylation site not found in the parent protein the rapeutic or (2) a carbohydrate moiety covalently linked to at least one nati ve glycosylation site found but not glycosylated in the parent protein thera peutic. The present invention further provides compositions, including oral pharmaceutical compositions, comprising the synthetic Type I interferon rece ptor polypeptide agonist, the hyperglycosylated polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present inven tion further provides containers, devices, and kits comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polyp eptide variant, or the hyperglycosylated, protease-resistant polypeptide var iant. The present invention further provides therapeutic methods involving a dministering an effective amount of an oral pharmaceutical composition compr ising a synthetic Type I interferon receptor polypeptide agonist, a hypergly cosylated polypeptide variant, or a hyperglycosylated, protease-resistant po lypeptide variant to an individual in need thereof.
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