Interferon beta-like molecules

A variant IFNB molecule which is a fusion protein comprising a) an IFNB polypeptide and b) a human serum albumin polypeptide.

A composition comprising an IFNB polypeptide that comprises the substitution C17S (relative to SEQ ID NO:2), the composition comprising a reduced amount of stabilizer as compared to the amount required to prepare a pharmaceutical composition comprising an IFNB polypeptide comprising C17.

A composition comprising an IFNB polypeptide that comprises the substitution C17S (relative to SEQ ID NO:2), the composition being substantially free from a stabilizer.

A conjugate exhibiting IFNB activity comprising at least one first non-polypeptide moiety conjugated to at least one lysine residue of an IFNB polypeptide, the amino acid sequence of which differs from that of wild-type human IFNB in at least one introduced and/or at least one removed lysine residue.

A conjugate exhibiting interferon β activity, comprising at least one polymer molecule and at least one sugar moiety covalently attached to an interferon β polypeptide, the amino acid sequence of which differs from that of wild-type human interferon β in

• a) at least one introduced and/or at least one removed amino acid residue comprising an attachment group for the polymer molecule, and
• b) at least one introduced and/or at least one removed amino acid residue comprising an attachment group for the sugar moiety,
• provided that when the attachment group for the polymer molecule is a cysteine residue, and the sugar moiety is an N-linked sugar moiety, a cysteine residue is not inserted in such a manner that an N-glycosylation site is destroyed.

A conjugate exhibiting interferon β activity, comprising an interferon β polypeptide comprising a sequence which differs from that of a wild-type human interferon β sequence in at least one introduced glycosylation site, the conjugate further comprising at least one un-PEGylated sugar moiety attached to an introduced glycosylation site.

A conjugate exhibiting interferon β activity, comprising an interferon β polypeptide comprising a sequence which differs from that of a wild-type human interferon β sequence in that a glycosylation site has been introduced or removed by way of introduction or removal of amino acid residue(s) constituting a part of a glycosylation site in a position that in the wildtype human interferon β sequence is occupied by a surface exposed amino acid residue.

A method of reducing immunogenicity and/or of increasing functional in vivo half-life and/or serum half-life of an interferon β polypeptide, the method comprising introducing an amino acid residue constituting an attachment group for a first non-polypeptide moiety into a position exposed at the surface of the protein that does not contain such group and removing an amino acid residue constituting an attachment group for a first non-polypeptide moiety and subjecting the resulting modified polypeptide to conjugation with the first non-polypeptide moiety.

A cell culture composition comprising a) a host cell transformed with a nucleotide sequence encoding a polypeptide exhibiting interferon β activity and b) medium comprising said polypeptide produced by expression of said nucleotide sequence, said culture composition directly resulting from secretion of said polypeptide from said host cell, and wherein the amount of said polypeptide is at least 800,000 IU/ml of medium, in particular in the range of 800,000-3,500,000 IU/ml medium.