Sialylated glycoproteins

Abstract

Pharmaceutical preparations containing polypeptides having particular sialylation patterns, and methods for the treatment of immune-related thrombocytopenia with such preparations, are described.

What is claimed is: 
     
         1 . A pharmaceutical preparation formulated for subcutaneous administration, said preparation comprising polypeptides comprising an Fc region, wherein at least 50% of branched glycans on the Fc region are di-sialylated by way of NeuAc-α 2,6-Gal terminal linkages. 
     
     
         2 . The pharmaceutical preparation of  claim 1 , wherein said polypeptides are present in said pharmaceutical preparation at a concentration of 50-250 mg/mL. 
     
     
         3 . The pharmaceutical preparation of  claim 1 , wherein less than 50% of branched glycans on the Fc region are mono-sialylated on the α 1,3 arm by way of a NeuAc-α 2,6-Gal terminal linkage. 
     
     
         4 . The pharmaceutical preparation of  claim 1 , wherein less than 50% of branched glycans on the Fc region are mono-sialylated on the α 1,6 arm by way of a NeuAc-α 2,6-Gal terminal linkage. 
     
     
         5 . A pharmaceutical preparation comprising polypeptides having an Fc region, wherein at least 50% of branched glycans on the Fc region are di-sialylated by way of NeuAc-α 2,6-Gal terminal linkages and less than 50% of branched glycans on the Fc region are mono-sialylated on the α 1,3 arm by way of a NeuAc-α 2,6-Gal terminal linkage. 
     
     
         6 . A pharmaceutical preparation comprising polypeptides having an Fc region, wherein at least 50% of branched glycans on the Fc region are di-sialylated by way of NeuAc-α 2,6-Gal terminal linkages and less than 50% of branched glycans on the Fc region are mono-sialylated on the α 1,6 arm by way of a NeuAc-α 2,6-Gal terminal linkage. 
     
     
         7 . A pharmaceutical preparation comprising polypeptides having an Fc region, wherein at least 85% of branched glycans on the Fc region are di-sialylated by way of NeuAc-α 2,6-Gal terminal linkages. 
     
     
         8 . The pharmaceutical preparation of  claim 1 , wherein said polypeptides consist essentially of an Fc region. 
     
     
         9 . The pharmaceutical preparation of  claim 1 , wherein said polypeptides further comprise a Fab region, a heterologous polypeptide sequence, or a non-polypeptide moiety. 
     
     
         10 . The pharmaceutical preparation of  claim 9 , wherein at least 10% of branched glycans on the Fab region or heterologous polypeptide sequence of said polypeptides are mono-sialylated or di-sialylated. 
     
     
         11 . The pharmaceutical preparation of  claim 9 , wherein less than 80% of branched glycans on the Fab region or heterologous polypeptide sequence of said polypeptides are mono-sialylated or di-sialylated. 
     
     
         12 . The pharmaceutical preparation of  claim 1 , wherein said polypeptides are recombinant polypeptides. 
     
     
         13 . The pharmaceutical preparation of  claim 1 , wherein said polypeptides are derived from plasma. 
     
     
         14 . The pharmaceutical preparation of  claim 12 , wherein said polypeptides are IgG polypeptides or said polypeptides consist essentially of an Fc region derived from IgG polypeptides. 
     
     
         15 . A method of increasing reticulated platelets in a subject in need thereof, comprising administering to the subject a pharmaceutical preparation of  claim 1 . 
     
     
         16 . A method of producing new platelets in a subject in need thereof, comprising administering to the subject a pharmaceutical preparation of  claim 1 . 
     
     
         17 . A method of increasing reticulated platelets or producing new platelets in a subject in need thereof, comprising administering to the subject a pharmaceutical preparation comprising polypeptides comprising an Fc region, wherein at least 85% of branched glycans on the Fc region are di-sialylated by way of NeuAc-α 2,6-Gal terminal linkages. 
     
     
         18 . The method of  claim 15 , wherein the subject is not being treated with thrombopoietin or a thrombopoietin receptor agonist or the subject did not respond to treatment with thrombopoietin or a thrombopoietin receptor agonist. 
     
     
         19 . The method of  claim 15 , wherein the subject has immune-related thrombocytopenia. 
     
     
         20 . The method of  claim 15 , further comprising, before and/or after the administering step, the step of determining the total platelet count and/or the reticulated platelet count in the subject. 
     
     
         21 . The method of  claim 20 , further comprising, after the determining step, the step of adjusting the dose of the administered pharmaceutical preparation. 
     
     
         22 . The pharmaceutical preparation of  claim 13 , wherein said polypeptides are IgG polypeptides or said polypeptides consist essentially of an Fc region derived from IgG polypeptides.