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STABILISIERTES INTERFERON-?

New gamma-interferon modified by polyethylene glycol, useful for treatment of pulmonary fibrosis, with increased in vivo stability, also nucleic acid encoding specific gamma-interferon homologs.
 
: Brunner, H.; Zakaria, H.; Otto, B.; Thomas, T.; Battermann, F.; Kresin, M.; Busche, A.; Schmalz, C.

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Frontpage ()

DE 2003-10320223 A: 20030505
WO 2004-EP4677 A: 20040503
WO 2004099245 A1: 20041118
C07K0014
German
Patent, Electronic Publication
Fraunhofer IGB ()

Abstract
Die vorliegende Erfindung bezieht sich auf ein stabilisiertes Interferon-?. Das erfindungsgemaesse Interferon-? ist an einer oder mehrerer seiner Aminosaeuren mit Thiol- oder Amino-Seitengruppen mit Polyethylenglykol modifiziert. Fuer eine derartige Modifizierung sind also insbesondere die Aminosaeuren Cystein, Asparagin, Glutamin, Lysin, Arginin und/oder Histidin geeignet.

 

WO2004099245 A UPAB: 20050117 NOVELTY - Interferon- gamma (I) modified by one or more poly(ethylene glycol) (PEG) molecules is new. DETAILED DESCRIPTION - An INDEPENDENT CLAIM is also included for a polynucleotide (II) that is homologous to the sequence of the gamma -interferon gene (or contains this gene or corresponds to it) in which the codon for amino acid (aa) 63 encodes Asn and/or the codon for aa 99 encodes Ser. ACTIVITY - Antiinflammatory; Respiratory-Gen. No suitable test details are given. MECHANISM OF ACTION - None given. USE - Interferon- gamma is known for treatment of pulmonary fibrosis. ADVANTAGE - (I) is stable and has biological activity comparable with that of the native (glycosylated) protein; contrast the non-glycosylated protein produced by recombinant expression in bacteria, which is much less stable, pharmacokinetically, than the native protein. Interferon- gamma variants that (a) contained the Glu7Cys and Ser69Cys mutations but was not modified by PEG (A1) or (b) contained these mutations and also Ser99Cys, and was PEG-modified on position 99, were injected subcutaneously into rats at 8 million international units/kg. Blood samples were taken periodically and interferon- gamma activity determined in an antiviral assay to show that the concentration of (A2) was lower during the first hour but that it remained in the blood for up to 48 hours, showing that it has much greater in vivo stability than (A1).

: http://publica.fraunhofer.de/documents/N-44895.html