Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Fusion protein or fusion polypeptide
Reexamination Certificate
1999-09-02
2001-09-04
Stucker, Jeffrey (Department: 1648)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Fusion protein or fusion polypeptide
C424S185100, C424S186100, C424S189100, C435S005000, C435S091320, C435S173300, C435S236000, C435S320100, C514S934000, C530S300000, C530S350000, C530S826000, C536S023400, C536S023720
Reexamination Certificate
active
06284249
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to a pharmaceutical composition intended for the treatment or prophylaxis of infections induced by the hepatitis C virus (HCV).
The hepatitis C virus (HCV) is the agent responsible for the majority of hepatitis infections of the non-A non-B type. The seroprevalence of HCV infections varies between 0.3 and 1.5% in the world population, possibly reaching 18% in some developing countries. Hundreds of millions of people are thus thought to be infected worldwide. Nine types and thirty subtypes of HCV have been described. The subtypes may be associated with a defined geographical distribution, type 1b being the most widespread worldwide. The progression to the chronic form occurs in 50% of cases, about 5 years after the primary infection. Persistent Chronic Hepatitis which is asymptomatic, but which exhibits a high circulating virus titer, is first observed, then Active Chronic Hepatitis becomes established. Twenty percent of chronic hepatites progress to sclerosis of the liver within about ten years. Hepatocarcinoma may develop in the cirrhotic liver.
The hepatitis C virus (HCV) is a positive single-stranded RNA virus. On the basis of structural resemblance, HCV has been linked to the flavivirus and pestivirus families.
SUMMARY OF THE INVENTION
The present invention relates to fusion polypeptide that comprises a first region having the C polypeptide of the hepatitis C virus (HCV) or a portion thereof that comprises a polypeptide region responsible for gene regulatory activity; and a second region having the envelope polypeptide (E1) of the virus or a portion thereof that comprises a site for cytoplasmic anchorage of the E1 polypeptide, wherein the first region is fused by a peptide bond to the second region, and the fusion polypeptide is not cleaved by a mammalian protease.
The present invention also relates to a fusion polypeptide comprising a C polypeptide of HCV or a portion thereof and an E1 envelope polypeptide of HCV or a portion thereof. The C polypeptide comprises a first C polypeptide region responsible for gene regulatory activity and a second C polypeptide region responsible for the interaction with the E1 envelope polypeptide, wherein the site of interaction with the E1 polypeptide is between about 151 and about 173, or between about 173 and about 191. The E1 envelope polypeptide comprises a first E1 polypeptide region responsible for E1 cytoplasmic anchorage and a second E1 polypeptide region responsible for the interaction of the second C polypeptide region. The site for interaction with the C polypeptide is between about amino acid 330 and about amino acid 380. The C polypeptide is fused by a peptide bond to the E1 envelope polypeptide, and the C polypeptide comprises Cysteine
172
Serine
173
-Phenylalanine
174
-Serine
175
with at least one mutation between amino acid Nos 172 and 175.
REFERENCES:
patent: 5645983 (1997-07-01), Liao et al.
patent: 5747339 (1998-05-01), Okayama et al.
patent: 0 484 787 A (1992-05-01), None
patent: 97/02887 (1997-03-01), None
patent: WO 98/39030 (1998-09-01), None
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Matsuura, et al., “Expression of Processed Envelope Protein of Hepatitis C in Mammalian and Insect Cells,”J Virol, 66:1425-1431 (1992).
Kohara, M., et al., “Expression and characterization of glycoprotein gp35 of hepatitis C virus using recombinant vaccinia virus,”J Gen Virol, 73:2313-2318 (1992).
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Hamilton Brook Smith & Reynolds P.C.
Pasteur Merieux Serums & Vaccins
Stucker Jeffrey
Winkler Ulrike
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