Interferon alpha 2b variants

Abstract

The present invention provides a fusion polypeptide comprising a first domain and a second domain, wherein the first domain comprises a polypeptide ligand which binds to a cell surface-associated antigen and the second domain comprises aglycosylated interferon α 2b (IFNα2b) having a sequence of SEQ ID NO: 1 or SEQ ID NO: 2. The aglycosylated IFNα2b further comprises one or more amino acid substitutions or deletions which attenuate the activity of the aglycosylated IFNα2b.

What is claimed: 
     
         1 . A method of treating a tumour in a subject, the method comprising:
 administering to the subject a fusion polypeptide comprising a first domain and a second domain, wherein the first domain comprises a polypeptide ligand which binds to a cell surface-associated antigen on cells of the tumour and the second domain comprises aglycosylated interferon α 2b (IFNα2b) having a sequence of SEQ ID NO: 1 or SEQ ID NO: 2 and wherein the aglycosylated IFNα2b further comprises one or more amino acid substitutions or deletions which attenuate the activity of the aglycosylated IFNα2b.   
     
     
         2 . The method of  claim 1 , wherein the tumour is selected from multiple myeloma or non-Hodgkin's lymphoma. 
     
     
         3 . A method of generating a polypeptide ligand-attenuated IFNα2b fusion polypeptide in mammalian cells, wherein the polypeptide ligand-attenuated IFNα2b fusion polypeptide has improved heterogeneity and/or enhanced FcRn binding, the method comprising:
 culturing a recombinant mammalian cell comprising a polynucleotide encoding the polypeptide ligand-attenuated IFNα2b fusion polypeptide wherein T106 of the IFNα2b sequence is replaced with another amino acid or is deleted such that on expression the IFNα2b component of the fusion protein is aglycosylated.