Interferon Beta-Like Molecules

Abstract

The invention relates to a conjugate exhibiting interferon β (IFNB) activity and comprising at least one first non-polypeptide moiety covalently attached to an IFNB polypeptide, the amino acid sequence of which differs from that of wildtype human IFNB in at least one introduced and at least one removed amino acid residue comprising an attachment group for said first non-polypeptide moiety. The first non-polypeptide moiety is e.g. a polymer molecule or a sugar moiety. The conjugate finds particular use in therapy. The invention also relates to a glycosylated variant of a parent IFNB polypeptide comprising at least one in vivo glycosylation site, wherein an amino acid residue of said parent polypeptide located close to said glycosylation site has been modified to obtain the variant polypeptide having an increased glycosylation as compared to the glycosylation of the parent polypeptide.

1 - 87 . (canceled) 
     
     
         88 . An interferon β polypeptide variant exhibiting interferon β activity, comprising a polypeptide sequence which differs from the polypeptide sequence of wild-type human interferon β polypeptide shown in SEQ ID NO:2 in no more than 15 amino acid residues, wherein the serine residue in position 2 of SEQ ID NO:2 is substituted with an amino acid residue in the variant, and wherein amino acid positions of the variant are numbered according to SEQ ID NO:2. 
     
     
         89 . The variant of  claim 88 , further comprising an amino acid substitution of the methionine residue in position 1 of SEQ ID NO:2. 
     
     
         90 . The variant of  claim 89 , wherein the amino acid substitution of the methionine in position 1 is M1K. 
     
     
         91 . The variant of  claim 88 , further comprising an amino acid substitution of the cysteine residue in position 17. 
     
     
         92 . The variant of  claim 91 , comprising the amino acid substitution C17S. 
     
     
         93 . The variant of  claim 89 , further comprising the amino acid substitution C17S. 
     
     
         94 . The variant of  claim 93 , further comprising an amino acid substitution of the methionine residue in position 36, 62, or 117. 
     
     
         95 . The variant of  claim 94 , further comprising an amino acid substitution of the methionine residue in each of positions 36, 62, and 117. 
     
     
         96 . The variant of  claim 94 , wherein the variant comprises an amino acid substitution of the methionine in position 117 which is M117T. 
     
     
         97 . The variant of  claim 96 , further comprising an amino acid substitution of the isoleucine residue in position 44. 
     
     
         98 . The variant of  claim 88 , further comprising at least one non-polypeptide moiety covalently attached to the variant. 
     
     
         99 . The variant according to  claim 98 , wherein the at least one non-polypeptide moiety comprises at least one polymer molecule. 
     
     
         100 . The variant of  claim 99 , wherein the polymer molecule comprises a polyethylene glycol (PEG) molecule. 
     
     
         101 . The variant of  claim 100 , wherein variant comprises PEG molecule covalently attached to the N-terminus of the variant. 
     
     
         102 . The variant of  claim 89 , further comprising a non-polypeptide moiety covalently attached to the variant, wherein said non-polypeptide moiety is a polymer molecule. 
     
     
         103 . The variant of  claim 102 , wherein the polymer molecule comprises a polyethylene glycol (PEG) molecule. 
     
     
         104 . The variant of  claim 103 , wherein the PEG molecule is covalently attached to the N-terminus of the variant. 
     
     
         105 . The variant of  claim 97 , further comprising a non-polypeptide moiety covalently attached to the variant, wherein said non-polypeptide moiety is a polymer molecule that is a polyethylene glycol (PEG) molecule. 
     
     
         106 . The variant of  claim 88 , wherein the variant comprises a derivatized amino acid residue. 
     
     
         107 . The variant of  claim 89 , wherein the variant comprises a derivatized amino acid residue. 
     
     
         108 . The variant of  claim 97 , wherein the variant comprises a derivatized amino acid residue. 
     
     
         109 . An interferon β polypeptide variant exhibiting interferon activity, comprising a polypeptide sequence which differs from the polypeptide sequence of wild-type human interferon β polypeptide shown in SEQ ID NO:2 in no more than 15 amino acid residues, wherein the methionine residue in position 1 of SEQ ID NO:2 is substituted with an amino acid residue in the variant, and wherein amino acid positions of the variant are numbered according to SEQ ID NO:2. 
     
     
         110 . The variant of  claim 109 , wherein the variant comprises a derivatized amino acid residue. 
     
     
         111 . The variant of  claim 109 , further comprising a non-polypeptide moiety covalently attached to the variant, wherein said non-polypeptide moiety is a polymer molecule comprising a polyethylene glycol (PEG) molecule. 
     
     
         112 . A nucleic acid comprising a nucleotide sequence encoding the polypeptide of  claim 88 . 
     
     
         113 . A method of treating a mammal with a disease for which interferon β is a useful treatment, the method comprising administering to the mammal an effective amount of the polypeptide of  claim 88 . 
     
     
         114 . The method of  claim 113 , wherein the disease is multiple sclerosis.