Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1997-06-05
2001-05-22
LeGuyader, John L. (Department: 1633)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S023700, C536S023100, C435S320100
Reexamination Certificate
active
06235888
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to gene constructs which are useful as anti-hepatitis C virus vaccine components in genetic immunization protocols, to methods of protecting individuals against hepatitis C virus infection and to methods of treating individuals suffering from hepatitis C virus infection.
BACKGROUND OF THE INVENTION
Hepatitis C virus (HCV), the major etiologic agent of transfusion acquired non-A, non-B hepatitis. is responsible for approximately 150,000 new cases of acute viral hepatitis annually in the United States (Greenberger, N.J., 1983, “New Approaches for Hepatitis C”,
Contemporary Internal Medicine
Feb:64). Approximately half of these infections progress to a chronic infection that can be associated with cirrhosis and/or hepatocellular carcinoma.
HCV is an enveloped, positive stranded RNA virus which has recently been classified as a separate genus within the Flavivirus family (Heinz, F. X., 1992 “Comparative Molecular Biology of Flaviviruses and Hepatitis C Virus”,
Arch. Virol. (Suppl.)
4:163). The viral genome is approximately 9,500 nucleotides in length and contains one long open reading frame that encodes a precursor polyprotein of 330 Kd. Individual HCV polypeptides are produced by proteolytic processing of the precursor polypeptide. This proteolysis is catalyzed by a combination of both cellular and viral encoded proteases.
In addition to the translated region, the HCV genome also contains both a 5′ untranslated region (5′ UTR) and a 3′ untranslated region (3′ UTR). The 5′ UTR represents the most highly conserved sequence among all HCV isolates reported to date, and thus has been postulated to contain important regulatory elements for replication and/or translation of HCV RNAs. The 5′ UTR also contains several small open reading frames (orf) but there is presently no evidence to suggest that these orf sequences are actually translated.
Development of a vaccine strategy for HCV is complicated not only by the significant heterogeneity among HCV isolates, but also by the mixture of heterogeneous genomes within an isolate (Martell, M. et al., 1992 “Hepatitis C Virus (HCV) Circulates as a Population of Different But Closely Related Genomes: Quasispecies Nature of HCV Genome Distribution”,
J. Virol.
66:3225). In addition, the virus contains a highly variable envelope region.
Vaccination and immunization generally refer to the introduction of a non-virulent agent against which an individual's immune system can initiate an immune response which will then be available to defend against challenge by a pathogen. The immune system identifies invading “foreign” compositions and agents primarily by identifying proteins and other large molecules which are not normally present in the individual. The foreign protein represents a target against which the immune response is made.
PCT Patent Application PCT/US90/01348 discloses sequence information of clones of the HCV genome, amino acid sequences of HCV viral proteins and methods of making and using such compositions including anti-HCV vaccines comprising HCV proteins and peptides derived therefrom.
U.S. Ser. No. 08/008,342 filed Jan. 26, 1993, U.S. Ser. No. 08/029,336 filed Mar. 11, 1993, U.S. Ser. No. 08/125,012 filed Sep. 21, 1993, PCT Patent Application Serial Number PCT/US94/00899 filed Jan. 26, 1994, and U.S. Ser. No. 08/221,579 filed Apr. 1, 1994 each contains descriptions of genetic immunization protocols. Vaccines against HCV are disclosed in each.
There remains a need for vaccines useful to protect individuals against hepatitis C virus infection. There remains a need for methods of protecting individuals against hepatitis C virus infection.
SUMMARY OF THE INVENTION
The present invention relates to nucleic acid molecules comprising an incomplete hepatitis C viral genome including SEQ ID NO: 1.
The present invention relates to nucleic acid molecules comprising an incomplete hepatitis C viral genome including a nucleotide sequence that encodes the HCV core protein and at least the last 9 nucleotides of the 5′ untranslated region.
The present invention relates to pharmaceutical compositions that comprise a nucleic acid molecule having an incomplete hepatitis C viral genome and at least the coding sequences of SEQ ID NO: 1 operably linked to regulatory elements functional in human cells.
The present invention relates to pharmaceutical compositions that comprise a nucleic acid molecule having an incomplete hepatitis C viral genome including a nucleotide sequence that encodes the HCV core protein and at least the last 9 nucleotides of the 5′ untranslated region. operably linked to regulatory elements functional in human cells.
The present invention relates to a method of immunizing an individual susceptible to or infected by hepatitis C virus comprising the step of administering to the individual, an amount of plasmid pHCV2-1 or plasmid pHCV4-2 effective to induce a protective or therapeutic immune response against hepatitis C virus infection.
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Okamoto et al., “Nucleotide sequence of the genomic RNA of hepatis C virus isolated from a human carrier: comparison with reported isolates for conserved and divergent regions”,J. of General Virology, 1991, vol. 72, pp. 2697-2704.
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Heinz, F.X., “Comparative Molecular Biology of Flaviviruses and Hepatitis C Virus”,Arch. Virol.(Suppl.) 4: 163-171 (1992).
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Blum, H. et al., “Hepatitis B Virus X Protein is not Central to the Viral Life Cycle in Vitro”,J. of Virol., 1992, 66, 123-127.
Blum, H. et al., “Persistence of Hepatitis B Viral DNA After Serological Recovery from Hepatitis B Virus Infection”,Hepatology, 1991, 14(1), 56-63.
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Chen, H.-S. et al., “The Woodchuck Hepatitis Virus X Gene is Important for Establishment of Virus Infection in Woodchuck”,J. Virology, 1993, 67(3), 1218-1226.
Chiba, J. et al., “Serodiagnosis of Hepatitis C Virus (HCV) Infection with an HCV Core Protein Molecularly Expressed by a Recombinant Baculovirus”,PNAS USA, 1991, 88, 4641-4645.
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Bukh, J. et al.,
Coney Leslie R.
Pachuk Catherine J.
Wakita Takaji
Wands Jack
Zurawski, Jr. Vincent R.
LeGuyader John L.
The General Hospital Corporation
Wilson Michael C.
Woodcock Washburn Kurtz Mackiewicz & Norris LLP
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