Low-toxicity human interferon-alpha analogs

A polypeptide analog of a native human interferon (IFN)-α protein,

• wherein the sequence of amino acids in the analog that corresponds to the sequence of residues 1-27 of the native IFN-α protein differs therefrom at one or more of positions 19, 20, 22, 24, and 27, said sequences differing only at said positions, provided that said sequence in the analog does not differ from said corresponding sequence in the native IFN-α only by the presence of Ser, Thr, Asn, Gln, or Gly at the amino acid residue corresponding to position 22;
• and wherein the analog is capable of exhibiting lower toxicity relative to the native IFN-α in an assay comprising:
• (a) incubating a first sample of PBMCs for seven days in a culture medium comprising at least 2000 antiviral units/ml of the analog;
• (b) incubating a second sample of PBMCs for seven days in a culture medium having an equal concentration, as antiviral units/ml, of the native IFN-α;
• and
• (c) comparing the percentage of viable cells remaining in the first sample with that in the second sample, whereby a higher percentage of viable cells indicates the relatively lower toxicity of the IFN species in the culture medium.