Rational evolution of cytokines for higher stability, the cytokines and encoding nucleic acid molecules
First Claim
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1. A modified interferon beta (IFN beta) cytokine, comprising one or more amino acid replacements in its sequence of amino acid residues, wherein:
- the modified IFN beta cytokine exhibits increased resistance to proteolysis compared to the unmodified IFN beta cytokine that does not comprise the one or more amino acid replacements;
one amino acid replacement is L6Q; and
the one or more amino acid replacements occur in a mature IFN beta cytokine having the sequence set forth in SEQ ID NO;
196 or in a sequence-related IFN beta cytokine at corresponding amino acid position(s) relative to SEQ ID NO;
196.
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Abstract
Compositions of modified cytokines and uses thereof generated using 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 are modified cytokines formulated for oral delivery and uses thereof to treat diseases and conditions mediated by cytokines.
107 Citations
43 Claims
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1. A modified interferon beta (IFN beta) cytokine, comprising one or more amino acid replacements in its sequence of amino acid residues, wherein:
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the modified IFN beta cytokine exhibits increased resistance to proteolysis compared to the unmodified IFN beta cytokine that does not comprise the one or more amino acid replacements; one amino acid replacement is L6Q; and the one or more amino acid replacements occur in a mature IFN beta cytokine having the sequence set forth in SEQ ID NO;
196 or in a sequence-related IFN beta cytokine at corresponding amino acid position(s) relative to SEQ ID NO;
196. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43)
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Specification