Interferon-β mutants with increased anti-proliferative activity
First Claim
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1. A modified interferon beta (IFN beta) cytokine, wherein said modified IFN beta cytokine differs from an unmodified IFN beta cytokine by two amino acid substitutions,wherein said unmodified IFN beta cytokine comprises the amino acid sequence of SEQ ID NO:
- 196,said two amino acid substitutions being either;
(a) substitution of the 5th and 6th positions in SEQ ID NO;
196, with aspartic acid and glutamine, respectively;
or(b) substitution of the 5th and 6th positions in SEQ ID NO;
196, with glutamine;
or(c) substitution of the 5th and 6th positions in SEQ ID NO;
196, with asparagine and glutamine, respectively;
or(d) substitution of the 6th and 36th positions in SEQ ID NO;
196, with glutamine and isoleucine, respectively;
or(e) substitution of the 6th and 86th positions in SEQ ID NO;
196, with glutamine;
and wherein said two amino acid substitutions confer increased resistance to proteolysis over the unmodified IFN beta cytokine.
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Abstract
Protease resistant modified interferon-beta polypeptides, pharmaceutical compositions and methods of treatment by administering the compositions are provided. The modified interferon-beta polypeptides are orally available; hence pharmaceutical compositions formulated for oral administration also are provided.
92 Citations
12 Claims
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1. A modified interferon beta (IFN beta) cytokine, wherein said modified IFN beta cytokine differs from an unmodified IFN beta cytokine by two amino acid substitutions,
wherein said unmodified IFN beta cytokine comprises the amino acid sequence of SEQ ID NO: - 196,
said two amino acid substitutions being either; (a) substitution of the 5th and 6th positions in SEQ ID NO;
196, with aspartic acid and glutamine, respectively;
or(b) substitution of the 5th and 6th positions in SEQ ID NO;
196, with glutamine;
or(c) substitution of the 5th and 6th positions in SEQ ID NO;
196, with asparagine and glutamine, respectively;
or(d) substitution of the 6th and 36th positions in SEQ ID NO;
196, with glutamine and isoleucine, respectively;
or(e) substitution of the 6th and 86th positions in SEQ ID NO;
196, with glutamine;and wherein said two amino acid substitutions confer increased resistance to proteolysis over the unmodified IFN beta cytokine. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
- 196,
Specification