IP Library › Granted Patent US 8,105,573
Granted Patent B2
US 8,105,573 · App. 13/014,392 · Granted Jan 31, 2012

Protease resistant modified IFN beta polypeptides and their use in treating diseases

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Quick Facts
Patent No.
US 8,105,573
App. No.
13/014,392
Granted
Jan 31, 2012
Kind
B2
Abstract

Protease resistant modified interferon-beta polypeptides, and pharmaceutical compositions containing such modified interferon-beta polypeptides are provided. The modified interferon-beta polypeptides contain amino acid substitutions that confer increased resistance to proteolysis over unmodified IFN beta cytokine molecules. The present invention provides for pharmaceutical formulations suitable for oral, nasal and pulmonary administration, and the use of such formulations in the treatment of disease.

Claims (13)

1. A modified interferon beta (IFN-β) cytokine, wherein said modified interferon beta cytokine differs from an unmodified IFN beta cytokine by two amino acid substitutions,

wherein said unmodified interferon beta cytokine comprises the amino acid sequence of SEQ ID NO: 196,

wherein said two amino acid substitutions are selected from the group consisting of:

(a) substitution of the 5th and 10th positions in SEQ ID NO: 196 with asparagine and aspartic acid, respectively;

(b) substitution of the 6th and 86th positions in SEQ ID NO: 196 with glutamic acid and glutamine, respectively;

(c) substitution of the 5th and 36th positions in SEQ ID NO: 196 with aspartic acid and isoleucine, respectively;

(d) substitution of the 5th and 108th positions in SEQ ID NO: 196 with glutamine and serine, respectively;

(e) substitution of the 6th and 108th positions in SEQ ID NO: 196 with glutamic acid and serine, respectively; and

(f) substitution of the 5th and 108th positions in SEQ ID NO: 196 with glutamic acid and serine, respectively;

and wherein said two amino acid substitutions confer increased resistance to proteolysis over the unmodified IFN beta cytokine.

2. The modified IFN-β polypeptide of claim 1 , wherein said modified IFN-β polypeptide is pegylated, albuminated and/or glycosylated.

3. A pharmaceutical composition comprising the modified IFN-β polypeptide of claim 1 , and a pharmaceutically acceptable excipient.

4. The pharmaceutical composition of claim 3 , wherein said composition is a formulation for oral, nasal or pulmonary administration.