Protease resistant modified interferon alpha polypeptides
AssigneeHanall Pharmaceuticals, Co., Ltd.
InventorsRene Gantier, Manuel Vega, Lila Drittanti, Thierry Guyon
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Abstract
Processes and systems for the high throughput directed evolution of peptides and proteins, particularly cytokines that act in complex biological settings, are provided. Also provided is a rational method for generating protein variants and the resulting variants.
Claims24
An isolated interferon (IFN) alpha cytokine, comprising an amino acid replacement in its sequence of amino acids, wherein:
- an amino acid replacement is E41 Q, whereby the interferon alpha cytokine exhibits increased resistance to proteolysis so that it can be administered orally compared to the unmodified interferon alpha cytokine that does not comprise the amino acid replacement;
- and
- in the interferon-alpha cytokine,
- the interferon is not glycosylated at E41Q;
- and
- the unmodified interferon alpha cytokine is selected from among an interferon α-2b (IFNα-2b), an interferon α-2a (IFNα-2a), an interferon α-2c (IFNα-2c) and consensus interferon whose sequences are set forth in SEQ ID Nos. 1, 182, 185 and 232, respectively.
An interferon alpha cytokine selected from among IFNα-2b, IFNα-2a, IFNα-2c, consensus interferon, IFNα-c, IFNα-d, IFNα-5, IFNα-6, IFNα-4, IFNα-4b, IFNα-I, IFNα-J, IFNα-H, IFNα-F and IFNα-8, each comprising the modification E41Q, wherein:
- the sequence of a human wild-type interferon alpha for each of IFNα-2b, IFNα-2a, IFNα-2c, consensus interferon, IFNα-c, IFNα-d, IFNα-5, IFNα-6, IFNα-4, IFNα-4b, IFNα-I, IFNα-J, IFNα-H, IFNα-F and IFNα-8;
- is set forth in SEQ ID Nos. 1, 182, 185, 232, 183 and 186-195, respectively;
- the modification at E41Q increases protease resistance of the interferon alpha cytokine so that it can be administered orally.
- the interferon alpha cytokine is not glycosylated at E41Q;
- and
- residue 1 in each SEQ ID corresponds to residue 1 of the mature interferon-alpha.
An interferon alpha cytokine, comprising the sequence of amino acids set forth in SEQ ID NO:87.
Dependencies are inferred from the claim text.