Recombinant interferon alpha2 (ifnalpha2) mutants and methods of use thereof
AssigneeYeda Research and Development Co. Ltd. at the Weizmann Institute of Science
InventorsGideon E Schreiber, Laila C. Roisman, Diego Jaitin, Eyal Kalie
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Abstract
The present invention provides IFNα2 mutants and active fragments, analogs, derivatives, and variants thereof, nucleotide molecules encoding same, pharmaceutical compositions containing the same, and methods utilizing the same for treating cancer, infectious diseases, and autoimmune diseases.
Claims76
A mutated interferon α2 (IFNα2) polypeptide, comprising a mutation selected from the group consisting of (a) mutation of the histidine at position 57 to a residue selected from the group consisting of tyrosine and methionine;
- (b) mutation of the glutamate at position 58 to a residue selected from the group consisting of asparagine, aspartate, leucine, and alanine;
- and (c) mutation of the glutamine at position 61 to a residue selected from the group consisting of serine, leucine, and aspartate;
- and combinations thereof of mutations (a), (b), and (c).
A mutated interferon α2 (IFNα2) polypeptide comprising a mutation selected from the group consisting of (a) mutation of the histidine at position 57;
- (b) mutation of the glutamate at position 58;
- and (c) mutation of the glutamine at position 61;
- (d) mutation of the asparagine at position 65;
- (e) mutation of the leucine at position 80;
- (f) mutation of the tyrosine at position 85;
- and (g) mutation of the tyrosine at position 89;
- and combinations thereof of any of mutations (a)-(g), wherein the mutation decreases affinity of the mutated IFNα2 polypeptide for the IFNAR1 subunit of the interferon receptor 1 (IFNAR).
A mutated interferon α2 (IFNα2) polypeptide, comprising a mutation of a residue selected from the group consisting of E159, S160, L161, S163, and E165, and combinations thereof, to a residue selected from the group consisting of lysine and arginine.
A mutated interferon α2 (IFNα2) polypeptide, comprising a substitution mutation of the 5-10 C-terminal residues of the mutated IFNα2 polypeptide to a sequence selected from the group consisting of KRLKSKE (SEQ ID NO:
- 43) and KRLKSK (SEQ ID NO:
- 44).
Dependencies are inferred from the claim text.