Non-a, Non-b Hepatitis Virus Or Hepatitis C Virus Patents (Class 424/228.1)
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Patent number: 7108855Abstract: The present invention relates to a method for purifying recombinant HCV single or specific oligomeric envelope proteins selected from the group consisting of E1 and/or E2 and/or E1/E2, characterized in that upon lysing the transformed host cells to isolate the recombinantly expressed protein a disulphide bond cleavage or reduction step is carried out with a disulphide bond cleavage agent. The present invention also relates to a composition isolated by such a method. The present invention also relates to the diagnostic and therapeutic application of these compositions.Type: GrantFiled: November 29, 2001Date of Patent: September 19, 2006Assignee: Innogenetics N.V.Inventors: Geert Maertens, Fons Bosman, Erik Depla
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Patent number: 7108856Abstract: The invention relates to Hepatitis C virus epitopes which are specific in relation to CD4+ T lymphocytes, in addition to vaccinations which contain said epitopes.Type: GrantFiled: March 26, 2003Date of Patent: September 19, 2006Assignee: Immusystems GmbHInventors: Jörn Tilman Gerlach, Helmut Diepolder
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Patent number: 7101561Abstract: The present invention relates to a method for purifying recombinant HCV single or specific oligomeric envelope proteins selected from the group consisting of E1 and/or E2 and/or E1/E2, characterized in that upon lysing the transformed host cells to isolate the recombinantly expressed protein a disulphide bond cleavage or reduction step is carried out with a disulphide bond cleavage agent. The present invention also relates to a composition isolated by such a method. The present invention also relates to the diagnostic and therapeutic application of these compositions. Furthermore, the invention relates to the use of HCV E1 protein and peptides for prognosing and monitoring the clinical effectiveness and/or clinical outcome of HCV treatment.Type: GrantFiled: November 29, 2001Date of Patent: September 5, 2006Assignee: Innogenetics N.V.Inventors: Geert Maertens, Erik Depla, Fons Bosman
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Patent number: 7101551Abstract: The present invention provides a substance which inhibits the binding between E2/NS1 protein of hepatitis C virus and a cell infectious with hepatitis C virus, a cell expressing CD81, or CD81. The present invention can provide a novel medicament which has an anti-viral effects such as an inhibitory action against HCV infection.Type: GrantFiled: February 13, 2001Date of Patent: September 5, 2006Assignees: Mitsubishi Pharma Corporation, Japan as Represented by Director General of Agency of National Institute of Infectious DiseasesInventors: Seima Itami, Tatsurou Shibui, Makoto Seki, Yoshihisa Yotsumoto, Yoshiharu Matsuura, Tatsuo Miyamura
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Patent number: 7098303Abstract: Immunogenic polypeptides comprising hepatitis C virus (HCV) immunogens are described. The HCV immunogen comprises the amino acid sequence Xaa-Thr-Xaa-Val-Thr-Gly-Gly-Xaa-Ala-Ala-Arg-Thr-Thr-Xaa-Gly-Xaa-Xaa-Ser-Leu-P he-Xaa-Xaa-Gly-Xaa-Ser-Gln-Xaa-Ile-Gln-Leu-Ile (SEQ ID NO:8). The immunogenic polypeptide can be coupled to a bacterial toxoid, such as a diphtheria toxoid.Type: GrantFiled: May 9, 1995Date of Patent: August 29, 2006Assignee: Novartis Vaccines and Diagnostics, Inc.Inventors: Amy J. Weiner, Michael Houghton
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Patent number: 7094406Abstract: Viral proteins derived from an enterically transmitted non-A/non-B viral hepatitis agent (HEV) are disclosed. In one embodiment, the protein is immunologically reactive with antibodies present in individuals infected with the viral hepatitis agent. This protein is useful in a diagnostic method for detecting infection by the enterically transmitted agent. Specific epitopes have been identified that are reactive with sera of individual infected with different strains of HEV. Also disclosed are DNA probes derived from a cloned sequence of the viral agent. These probes are useful for identifying and sequencing the entire viral agent and for assaying the presence of the viral agent in an infected sample, by using probe-specific amplification of virus-derived DNA fragments.Type: GrantFiled: May 7, 2001Date of Patent: August 22, 2006Assignee: The United States of America as represented by the Secretary of the Department of Health and Human Services and Genelabs Technologies, Inc.Inventors: Gregory R. Reyes, Patrice O. Yarbough, Daniel W. Bradley, Krzysztof Z. Krawczynski, Albert W. Tam, Kirk E. Fry
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Patent number: 7084266Abstract: The present invention discloses nucleic acid sequence which encodes infectious hepatitis C virus of strain HC-J6CH, gentotype 2a, and the use of the sequence, and polypeptides encoded by all or part of the sequence, in the development of vaccines and diagnostics for HCV and in the development of screening assays for the identification of antiviral agents for HCV.Type: GrantFiled: February 6, 2000Date of Patent: August 1, 2006Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Masayuki Yanagi, Jens Bukh, Suzanne U. Emerson, Robert H. Purcell
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Patent number: 7074410Abstract: Provided are an isolated peptide having the amino acid sequence DLMGYIPAV (SEQ ID NO: 1), an isolated HCV core polypeptide comprising an L?A substitution at amino acid position 139, an isolated HCV core polypeptide having the amino acid sequence of SEQ ID NO: 2, and a fragment of an HCV core polypeptide having fewer amino acids than the entire HCV core polypeptide and comprising the amino acid sequence of SEQ ID NO:1. Also provided are nucleic acids which encode the peptides and polypeptides of this invention, vectors comprising the nucleic acids of this invention and cells comprising the vectors and nucleic acids of this invention. Further provided are methods of producing an immune response in a subject and/or treating or preventing HCV infection in a subject, comprising administering to the subject, or to a cell of the subject, any of the compositions of this invention.Type: GrantFiled: February 2, 2004Date of Patent: July 11, 2006Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Jay A. Berzofsky, Stephen M. Feinstone, Marian E. Major, Pablo Sarobe
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Patent number: 7070790Abstract: The nucleotide and deduced amino acid sequences of cDNAs encoding the envelope 1 genes and core genes of isolates of hepatitis C virus (HCV) are disclosed. The invention relates to the oligonucleotides, peptides and recombinant envelope 1 and core proteins derived from these sequences and their use in diagnostic methods and vaccines.Type: GrantFiled: May 26, 1998Date of Patent: July 4, 2006Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Jens Bukh, Roger H. Miller, Robert H. Purcell
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Patent number: 7056658Abstract: Multiple epitope fusion proteins and immunoassays using the same are disclosed. The multiple epitope fusion proteins are encompassed by the general structural formula (A)x?(B)y?C2 which represents a linear amino acid sequence, wherein B is an amino acid sequence of an epitope or cluster of epitopes and each B contains at least five and not more than 1,000 amino acids, y is an integer of 2 or more, A and C are each independently an amino acid sequence of an epitope or cluster of epitopes not adjacent to B in nature and x and z are each independently an integer of 0 or more wherein at least one of x and z is 1 or more.Type: GrantFiled: June 17, 2002Date of Patent: June 6, 2006Assignee: Chiron CorporationInventors: Pablo D. T. Valenzuela, David Ying Chien
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Patent number: 7052696Abstract: Antigenic epitopes of hepatitis C virus (HCV) and mosaic HCV polypeptides useful as reagents in assays for the diagnosis or monitoring of HCV in a biological sample. The antigenic epitopes and mosaic polypeptides are also useful for the construction of immunogenic pharmaceutical compositions, such as vaccines. The mosaic polypeptides are artificial composite proteins constructed from diagnostically relevant antigenic regions derived from different HCV proteins. Preferably, the mosaic polypeptides contain antigenic epitopes from the core protein, NS3 protein, and NS4 protein. The preferred mosaic polypeptides optionally contain an additional antigenic epitope from either the NS4 protein or the NS5a protein or both.Type: GrantFiled: January 10, 2001Date of Patent: May 30, 2006Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Howard A. Fields, Yury E. Khudyakov
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Patent number: 7048930Abstract: The present invention relates to the general field of recombinant protein expression, purification of recombinant proteins, diagnosis of HCV infection, prophylactic treatment against HCV infection and to the prognosing/monitoring of the clinical efficiency of treatment of an individual with chronic hepatitis, or the prognosing/monitoring of the natural disease. In particular, the present invention relates to the use of yeast, i.e. Hansenula or Saccharomyces glycosylation minus strains, for the efficient expression of HCV envelope proteins that are core-glycosylated, purification methods for these proteins, and the use in various applications, such as the use in diagnosis, prophylaxis or therapy of HCV envelope proteins purified according to the present invention.Type: GrantFiled: April 24, 2002Date of Patent: May 23, 2006Assignee: Innogenetics N.V.Inventors: Fons Bosman, Erik Depla, Geert Deschamps, Erwin Sablon, Isabelle Samson, Annie Van Broekhoven, Joost Haelewyn
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Patent number: 7034108Abstract: Peptides which are mimotopes of the hypervariable region 1 (HVR1) of the putative envelope protein E2 of hepatitis C virus (HCV) are provided, useful in obtaining antibodies and raising an immune response cross-reactive against different strains of HCV.Type: GrantFiled: May 14, 1999Date of Patent: April 25, 2006Assignee: Istituto di Ricerche di Biologia Molecolare P. Angeletti S.p.A.Inventors: Alfredo Nicosia, Armin Lahm, Anna Tramontano, Riccardo Cortese
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Patent number: 7029678Abstract: The present invention provides vaccine compositions comprising an oil-in-water emulsion optionally with 3 De-O-acylated monophosphoryl lipid A and QS21. The vaccine compositions are potent induces of a range of immune responses.Type: GrantFiled: September 3, 2003Date of Patent: April 18, 2006Assignee: SmithKline Beecham Biologicals (S.A.)Inventors: Patricia Marie Momin, Nathalie Marie-Josephe Garcon
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Patent number: 6986892Abstract: Polypeptides comprising a mutant non-structural Hepatitis C virus useful in diagnostic and/or immunogenic compositions are disclosed, in which the mutant is an N-terminal mutation that functionally disrupt the catalytic domain of NS3. Polynucleotides encoding these polypeptides, host cells transformed with polynucleotides and methods of using the polypeptides and polynucleotides are also disclosed.Type: GrantFiled: November 22, 2000Date of Patent: January 17, 2006Assignee: Chiron CorporationInventors: Doris Coit, Angelica Medina-Selby, Mark Selby, Michael Houghton
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Patent number: 6974864Abstract: The present invention relates to new genomic nucleotide sequences and amino acid sequences corresponding to the coding region of these genomes. The invention relates to new HCV types and subtypes sequences which are different from the known HCV types and subtypes. More particularly, the present invention relates to new HCV type 7 sequences, new HCV type 9 sequences, new HCV type 10 and new HCV type 11 sequences. Also, the present invention relates to new HCV type 1 sequences of subtypes 1d, 1e, 1f and 1g; new HCV type 2 sequences of subtypes 2e, 2f, 2g, 2h, 2I, 2k and 2l; new HCV type 3 sequences of subtype 3g, new HCV type 4 sequences of subtypes 4k, 4l and 4m; a process for preparing them, and their use for diagnosis, prophylaxis and therapy. More particularly, the present invention provides new type-specific sequences of the Core, the E1 and the NS5 regions of new HCV types 7, 9, 10 and 11, as well as of new variants (subtypes) of HCV types 1, 2, 3 and 4.Type: GrantFiled: May 9, 2001Date of Patent: December 13, 2005Assignee: Innogenetics N.V.Inventors: Geert Maertens, Lieven Stuyver
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Patent number: 6964852Abstract: The invention concerns a structural peptide, identified by antibodies directed against a polypeptide, comprising the 2-45 amino acid sequence of the N-terminal end of the Core or nucleocapsid (p21) protein of the hepatitis C virus (HCV), excluding any protein or peptide compound comprising or consisting of the N-terminal end. The invention is characterized in that it comprises a tertiary structure consisting of at least a first peptide fragment having a secondary structure in ? helix, a second peptide fragment having secondary structure in ? helix and a third peptide bond fragment linking the two ? helices, these two ? helices being substantially perpendicular to each other in space. This peptide can be used for detecting antibodies directed against the p21 protein of HCV, for detecting all of part of the RNA of HCV and for preparing a diagnostic, prophylactic or therapeutic composition for detecting, preventing or treating an HCV infection.Type: GrantFiled: February 19, 2003Date of Patent: November 15, 2005Assignee: Bio MerieuxInventors: Michel Jolivet, Francois Penin, Pascal Dalbon, Laurent Ladaviere, Xavier Lacoux
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Patent number: 6960659Abstract: A mosaic protein comprising a variety of immunoreactive antigenic epitopes from several genotypes of hepatitis C virus. The mosaic protein provides a sensitive and specific immunological hepatitis detection assay. A restriction enzyme assisted ligation method of making an artificial gene permits controlled construction of mosaic proteins, and allows confirmatory expression of the intermediate gene products.Type: GrantFiled: January 25, 2000Date of Patent: November 1, 2005Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Yury E. Khudyakov, Howard A. Fields
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Patent number: 6956117Abstract: A unique HCV RNA molecule is provided having an enhanced efficiency of establishing cell culture replication. Novel adaptive mutations have been identified within the HCV non-structural region that improves the efficiency of establishing persistently replicating HCV RNA in cell culture. This self-replicating polynucleotide molecule contains, contrary to all previous reports, a 5?-NTR that can be either an A as an alternative to the G already disclosed and therefore provides an alternative to existing systems comprising a self-replicating HCV RNA molecule. The G->A mutation gives rise to HCV RNA molecules that, in conjunction with mutations in the HCV non-structural region, such as the G(2042)C/R mutations, possess greater efficiency of transduction and/or replication. These RNA molecules when transfected in a cell line are useful for evaluating potential inhibitors of HCV replication.Type: GrantFiled: December 4, 2002Date of Patent: October 18, 2005Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: George Kukolj, Arnim Pause
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Patent number: 6946448Abstract: Methods of nucleic acid immunization comprising the in utero delivery of nucleic acid molecules that encode one or more selected antigens to a vertebrate fetus are disclosed.Type: GrantFiled: May 23, 2002Date of Patent: September 20, 2005Assignee: University of SaskatchewanInventors: Volker Gerdts, Lorne Babiuk, Sylvia van Drunen Littel-van den Hurk, Philip J. Griebel
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Patent number: 6943246Abstract: The invention relates to the discovery of a novel RNA sequence at the 3? terminal sequence of hepatitis C virus (HCV) genome RNA. Included in the invention are the 3? sequence, its complement, and their use for nucleic-acid based diagnostics and for developing and evaluating novel anti-HCV therapies. This sequence element, which is conserved among HCV genotypes, is likely to be essential for viral replication, and required for construction of full-length HCV cDNA clones capable of yielding infectious RNA, progeny virus or replication-competent HCV replicons. Such functional clones are useful tools for evaluation of therapeutic approaches and as substrates for developing candidate attenuated or inactivated HCV derivatives for vaccination against HCV.Type: GrantFiled: May 30, 2002Date of Patent: September 13, 2005Assignee: Washington UniversityInventors: Charles M. Rice, Alexander A. Kolykhalov
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Patent number: 6887484Abstract: A vaccine having a good vaccination effect, which comprises an antigen; a peptide selected from the group consisting of a peptide having the amino acid sequence of SEQ ID NO: 1, a peptide having the amino acid sequence of SEQ ID NO: 2, and a peptide derived from a peptide having the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2; and an immune activator.Type: GrantFiled: July 31, 2002Date of Patent: May 3, 2005Assignees: Posco, Pohang University of Science & TechnologyInventors: Yoe-Sik Bae, Youn-Dong Kim, You-Suk Seo, Young-Chul Sung, Pann-Ghill Suh, Sung-Ho Ryu, Taehoon Lee
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Patent number: 6881821Abstract: Newly elucidated sequences of hepatitis C virus type 4 and type 5 are described, together with those of a newly discovered type 6. Unique type-specific sequences in the NS4, NS5 and core regions enable HCV detection and genotyping into types 1 to 6. Antigenic peptides and immunoassays are described.Type: GrantFiled: May 5, 1994Date of Patent: April 19, 2005Assignees: Common Services Agency, Murex Diagnostics International Inc.Inventors: Peter Simmonds, Peng Lee Yap, Ian Hugo Pike
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Patent number: 6858590Abstract: Compositions and methods for enhancing the effect of vaccines in animals, such as domestic, sport, or pet species, and humans are disclosed. More particularly, vaccine compositions comprising ribavirin and an antigen, preferably an antigen that has an epitope present in Hepatitis C virus (HCV), are disclosed for use in treating and preventing disease, preferably HCV infection.Type: GrantFiled: August 15, 2001Date of Patent: February 22, 2005Assignee: TRIPEP ABInventors: Matti Sällberg, Catharina Hultgren
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Patent number: 6855318Abstract: Multimer peptides (e.g. 30- to 45-mer peptides) derived from hepatitis C virus envelope proteins reacting with the majority of anti-HCV antibodies present in patient sera are described. The usage of the latter peptides to diagnose, and to vaccinate against, an infection with hepatitis C virus is also disclosed.Type: GrantFiled: May 5, 2000Date of Patent: February 15, 2005Assignee: N.V. Innogenetics S.A.Inventors: Geert Maertens, Erik Depla
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Patent number: 6849429Abstract: Recombinant hepatitis C virus (HCV) capsid proteins that self-assemble into large spherical virus-like particles structures and viral capsids that include conformational antigenic epitopes are provided. The large spherical virus-like particles structures and viral capsids, including capsid proteins that are expression products of a viral particle coding sequence protein, may be prepared as vaccines to induce a cellular or humoral immune response. The self assembling capsid proteins may also be used as elements of diagnostic immunoassay procedures for HCV infection.Type: GrantFiled: November 15, 2000Date of Patent: February 1, 2005Assignee: Board of Regents, The University of Texas SystemInventors: Stanley J. Watowich, Meghan Kunkel, Marta Lorinczi
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Patent number: 6841353Abstract: Antibodies to two new epitopes on the HCV envelope proteins were identified which allow routine detection of native HCV envelope antigens, in tissue or cells derived from the host. The new epitopes are: the E1 region aa 307-326 and the N-terminal hyper variable region of E2 aa 395-415. Surprisingly, we characterised an antibody that reacts with various sequences of the hypervariable domain of E2. Specific monoclonal antibodies directed against these epitopes and allowing routine detection of viral antigen are described.Type: GrantFiled: December 13, 2002Date of Patent: January 11, 2005Assignee: Innogenetics N.V.Inventors: Geert Maertens, Erik Depla, Marie-Ange Buyse
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Patent number: 6828139Abstract: A nucleic acid having a first nucleotide sequence encoding an infectious hepatitis C virus, a second nucleotide sequence encoding a ribozyme, and an inducible promoter operably linked to the first and second nucleotide sequences, the ribozyme being configured to remove a 3′ sequence unnecessary for replication of the infectious hepatitis C virus from a transcript initiated by the inducible, is described. A cell containing the nucleic acid and methods of using the cell are also described.Type: GrantFiled: July 26, 2002Date of Patent: December 7, 2004Assignee: The General Hospital CorporationInventors: Emmett Vance Schmidt, Raymond Taeyong Chung
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Publication number: 20040241183Abstract: The present invention relates to an adjuvant derived from human lymphocytes. The adjuvant can be used in combination with traditional vaccines or cancer immunotherapy, to enhance the response of the patient's immune system to the vaccine or other immunotherapeutic agent. The adjuvant is derived from the supernatant collected from cultured activated lymphocytes.Type: ApplicationFiled: February 20, 2004Publication date: December 2, 2004Inventors: Kenichiro Hasumi, Lowell T. Harmison, Dean LeMar Mann, Kim Graulich Hankey, Kristina Michelle Holt
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Patent number: 6824768Abstract: There is disclosed a method for treating antiviral treatment naives patient having chronic hepatitis C infection to eradicate detectable HCV-RNA involving a combination therapy using (1) a therapeutically effective inducing amount of ribavirin and a therapeutically effective induction dosing amount of pegylated interferon-alfa, e.g, pegylated interferon-alfa-2b for a first treatment time period sufficient to substantially lower detectable HCV-RNA, followed by (2) administering a therapeutically effective amount of ribavirin and an therapeutically effective amount of pegylated interferon-alfa, e.g., pegylated interferon alfa-2b for a second treatment time period sufficient to eradicate detectable HCV-RNA at least by end of the second treatment time period and to maintain no detectable HCV-RNA for at least 24 weeks after the end of the second treatment time period.Type: GrantFiled: December 16, 1999Date of Patent: November 30, 2004Assignee: Schering CorporationInventors: Carlos O. Stalgis, Janice K. Albrecht, Paul W. Glue
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Patent number: 6797809Abstract: HCV immunoassays comprising an NS3/4a conformational epitope and a multiple epitope fusion antigen are provided, as well as immunoassay solid supports for use with the immunoassays.Type: GrantFiled: August 8, 2003Date of Patent: September 28, 2004Assignee: Chiron CorporationInventors: David Y. Chien, Phillip Arcangel, Laura Tandeske, Carlos George-Nascimento, Doris Coit, Angelica Medina-Selby
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Publication number: 20040185064Abstract: Recombinant adenovirus and methods of administration to a host are provided for eliciting immune response of the host to various pathogens. In one aspect of the invention, a vaccination method is provided for enhancing immunity of the host to the pathogen through rotation of the serotypes of the recombinant adenoviruses administered to the host.Type: ApplicationFiled: November 1, 2002Publication date: September 23, 2004Inventor: Danher Wang
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Patent number: 6787145Abstract: A strain of hepatitis E virus from Pakistan (SAR-55) implicated in an epidemic of enterically transmitted non-A, non-B hepatitis, now called hepatitis E, is disclosed. The invention relates to the expression of the whole structural region of SAR-55, designated open reading frame 2 (ORF-2), in a eukaryotic expression system. The expressed protein is capable of forming HEV virus-like particles which can serve as an antigen in diagnostic immunoassays and as an immunogen or vaccine to protect against infection by hepatitis E.Type: GrantFiled: November 28, 2000Date of Patent: September 7, 2004Assignee: The United States of America as represented by the Secretary of the Department of Health and Human ServicesInventors: Sergei A. Tsarev, Suzanne U. Emerson, Robert H. Purcell
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Publication number: 20040141999Abstract: In a method of treating viral infections and of tumors induced thereby a radioimmunoconjugate (RIC) containing an immunologically effective component and a radioactive component is provided. The immunologically effective component contains a) a receptor molecule or a fragment thereof having affinity to an epitope of the viral structural proteins expressed on the plasma membrane of infected cells, or b) a fragment of the cellular receptor molecule modified by mutagenesis, the fragment having affinity to an epitope of the viral structural proteins expressed on the plasma membrane of infected cells. The radioactive component is an alpha emitter or a beta emitter. The therapeutical agent is effective against viral infections such as HIV, HBV, HCV, HDV, HTLV, CMV, EBV, or HHV8 infections.Type: ApplicationFiled: January 8, 2004Publication date: July 22, 2004Inventor: Wolfgang Bergter
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Publication number: 20040126395Abstract: The present invention relates to a method for purifying recombinant HCV single or specific oligomeric envelope proteins selected from the group consisting of E1 and/or E2 and/or E1/E2, characterized in that upon lysing the transformed host cells to isolate the recombinantly expressed protein a disulphide bond cleavage or reduction step is carried out with a disulphide bond cleavage agent. The present invention also relates to a composition isolated by such a method. The present invention also relates to the diagnostic and therapeutic application of these compositions. Furthermore, the invention relates to the use of HCV E1 protein and peptides for prognosing and monitoring the clinical effectiveness and/or clinical outcome of HCV treatment.Type: ApplicationFiled: December 18, 2002Publication date: July 1, 2004Inventors: Geert Maertens, Erik Depla, Fons Bosman
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Publication number: 20040086529Abstract: The present invention relates to compositions and methods for enhancing the effect of vaccines in animals, such as domestic, sport, or pet species, and humans. More particularly, the use of Ribavirin as an adjuvant to a vaccine protocol and compositions having Ribavirin and an antigen are described.Type: ApplicationFiled: November 20, 2003Publication date: May 6, 2004Inventors: Matti Sallberg, Catharina Hultgren
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Patent number: 6706874Abstract: A unique HCV RNA molecule is provided having an enhanced efficiency of establishing cell culture replication. Novel adaptive mutations have been identified within the HCV non-structural region that improves the efficiency of establishing persistently replicating HCV RNA in cell culture. This self-replicating polynucleotide molecule contains, contrary to all previous reports, a 5′-NTR that can be either an A as an alternative to the G already disclosed and therefore provides an alternative to existing systems comprising a self-replicating HCV RNA molecule. The G→A mutation gives rise to HCV RNA molecules that, in conjunction with mutations in the HCV non-structural region, such as the G(2042)C/R mutations, possess greater efficiency of transduction and/or replication. These RNA molecules when transfected in a cell line are useful for evaluating potential inhibitors of HCV replication.Type: GrantFiled: December 21, 2001Date of Patent: March 16, 2004Inventors: George Kukolj, Arnim Pause
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Patent number: 6706873Abstract: A strain of hepatitis E virus from Pakistan (SAR-55) implicated in an epidemic of enterically transmitted non-A, non-B hepatitis, now called hepatitis E, is disclosed. The invention relates to the expression of the whole structural region of SAR-55, designated open reading frame 2 (ORF-2), in a eukaryotic expression system. The expressed protein is capable of forming HEV virus-like particles which can serve as an antigen in diagnostic immunoassays and as an immunogen or vaccine to protect against infection by hepatitis E.Type: GrantFiled: October 3, 1994Date of Patent: March 16, 2004Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Sergei A. Tsarev, Suzanne U. Emerson, Robert H. Purcell
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Patent number: 6692751Abstract: The present invention relates to recombinant expression vectors which express segments of deoxyribonucleic acid that encode recombinant HIV and HCV antigens. These recombinant expression vectors are transformed into host cells and used in a method to express large quantities of these antigens. The invention also provides compositions containing certain of the isolated antigens., diagnostic systems containing these antigens and methods of assaying body fluids to detect the presence of antibodies against the antigens of the invention.Type: GrantFiled: September 16, 1997Date of Patent: February 17, 2004Assignees: New York Blood CenterInventors: Suzanne Zebedee, Genevieve Inchauspe, Marc S. Nasoff, Alfred S. Prince, Torsten B. Helting, Michael F. Nunn
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Patent number: 6689368Abstract: The present invention relates to a polypeptide of about 8 to about 100 amino acids comprising or consisting of at least 8 contiguous amino acids selected from the core, and/or the NS3 regions of the HCV polyprotein, with said contiguous amino acids containing a T-cell stimulating epitope.Type: GrantFiled: November 19, 1997Date of Patent: February 10, 2004Assignee: Innogenetics N.V.Inventors: Geert Leroux-Roels, Robert Deleys, Geert Maertens
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Patent number: 6685944Abstract: The present invention provides 1) an isolated peptide having the amino acid sequence DLMGYIPAV, (SEQ ID NO: 1); 2) an isolated HCV core polypeptide comprising an L→A substitution at amino acid position 139; 3) an isolated HCV core polypeptide having the amino acid sequence of SEQ ID NO: 2; and 4) a fragment of an HCV core polypeptide having fewer amino acids than the entire HCV core polypeptide and comprising the amino acid sequence SEQ ID NO: 1. Also provided are nucleic acids which encode the peptides and polypeptides of this invention, vectors comprising the nucleic acids of this invention and cells comprising the vectors and nucleic acids of this invention. The present invention further provides methods of producing an immune response in a subject and/or treating or preventing HCV infection in a subject, comprising administering to the subject, or to a cell of the subject, any of the compositions of this invention.Type: GrantFiled: October 19, 2001Date of Patent: February 3, 2004Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Jay A. Berzofsky, C. David Pendleton, Stephen M. Feinstone, Marian E. Major, Pablo Sarobe
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Patent number: 6680059Abstract: The present invention relates to compositions and methods for enhancing the effect of vaccines in animals, such as domestic, sport, or pet species, and humans. More particularly, the use of Ribavirin as an adjuvant to a vaccine protocol and compositions having Ribavirin and an antigen are described.Type: GrantFiled: March 22, 2002Date of Patent: January 20, 2004Assignee: Tripep ABInventors: Matti Sällberg, Catharina Hultgren
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Publication number: 20030202987Abstract: The present invention is based on the finding that the envelope proteins of HCV induce a beneficial immune response in chronically HCV-infected chimpanzees. The immunization can preferentially be carried out using HCV envelope proteins in the form of particles which are produced in a detergent-assisted manner. The envelope proteins when presented as such to chronic HCV carriers are highly immunogenic and stimulate both the cellular and humoral immune response.Type: ApplicationFiled: April 16, 2003Publication date: October 30, 2003Applicant: INNOGENETICSInventors: Erik Depla, Geert Maertens, Alfons Bosman, Frans Van Wijnendaele
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Patent number: 6635257Abstract: The present invention is based on the finding that the envelope proteins of HCV induce a beneficial immune response in chronically HCV-infected chimpanzees. The immunization can preferentially be carried out using HCV envelope proteins in the form of particles which are produced in a detergent-assisted manner. The envelope proteins when presented as such to chronic HCV carriers are highly immunogenic and stimulate both the cellular and humoral immune response.Type: GrantFiled: July 23, 1999Date of Patent: October 21, 2003Assignee: Innogentics N.V.Inventors: Erik Depla, Geert Maertens, Alfons Bosman, Frans Van Wijnendaele
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Patent number: 6623739Abstract: The present invention provides vaccine compositions comprising an oil-in-water emulsion optionally with 3 De-O-acylated monophosphoryl lipid A and QS21. The vaccine compositions are potent inducers of a range of immune responses.Type: GrantFiled: February 24, 2000Date of Patent: September 23, 2003Assignee: SmithKline Beecham Biologicals s.a.Inventors: Patricia Marie Momin, Nathalie Marie-Josephe Garcon
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Publication number: 20030170870Abstract: GB virus C (GBV-C or hepatitis G virus) is a recently described flavivirus that frequently leads to chronic viremia in humans. Although associated with acute post-transfusion hepatitis, it is not clear if GBV-C is pathogenic for humans. A full-length cDNA was constructed from the plasma of a person with chronic GBV-C viremia. Peripheral blood mononuclear cells (PBMCs) transfected with full-length RNA transcripts from this GBV-C clone resulted in viral replication, demonstrating an isolated infectious GBV-C nucleic acid molecule. In addition to composition involving an isolated infectious GBV-C nucleic acid molecule, the present invention concerns methods of inhibiting and treating HIV infections.Type: ApplicationFiled: April 5, 2001Publication date: September 11, 2003Inventors: Jinhua Xiang, Sabina Wunschmann, Warren Schmidt, Jack Stapleton
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Patent number: 6613333Abstract: The present invention relates to a polypeptide of about 8 to about 100 amino acids comprising or consisting of at least 8 contiguous amino acids selected from the core, and/or the NS3 regions of the HCV polyprotein, with said contiguous amino acids containing a T-cell stimulating epitope.Type: GrantFiled: November 19, 1997Date of Patent: September 2, 2003Assignee: Innogenetics N.V.Inventors: Geert Leroux-Roels, Robert Deleys, Geert Maertens
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Publication number: 20030161834Abstract: The present invention relates to adjuvant compositions which are suitable to be used in vaccines. In particular, the adjuvant compositions of the present invention comprises a saponin and an immunostimulatory oligonucleotide, optionally with a carrier. Also provided by the present invention are vaccines comprising the adjuvants of the present invention and an antigen. Further provided are methods of manufacture of the adjuvants and vaccines of the present invention and their use as medicaments. Methods of treating an individual susceptible to or suffering from a disease by the administration of the vaccines of the present invention are also provided.Type: ApplicationFiled: March 3, 2003Publication date: August 28, 2003Applicant: SmithKline Beecham Biologicals s.a.Inventors: Martin Friede, Nathalie Garcon, Catherine Marie Ghislaine Gerard, Philippe Hermand
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Publication number: 20030152591Abstract: The present invention relates to genomic nucleotide sequences and amino acid sequences corresponding to the non-coding and coding region of a new type of HCV. The invention relates to new HCV types and subtypes sequences which are different from the known HCV types and subtypes sequences. Particularly, the present invention relates to said new HCV type sequences; a process for preparing them, and their use for diagnosis, prophylaxis and therapy. More particularly, the present invention provides new type-specific sequences of the 5′ NCR, Core, the E1 and the NS5 regions of the new HCV type. These new HCV sequences are useful to diagnose the presence of HCV type genotypes or serotypes in a biological sample. Moreover, the availability of these new type-specific sequences can increase the overall sensitivity of HCV detection and should also prove to be useful for prophylactic and therapeutic purposes.Type: ApplicationFiled: August 29, 2002Publication date: August 14, 2003Inventors: Erwin Sablon, Leen-Jan Van Doorn, Wim Quint
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Publication number: 20030147918Abstract: The present invention relates to a method for purifying recombinant HCV single or specific oligomeric envelope proteins selected from the group consisting of E1 and/or E2 and/or E1/E2, characterized in that upon lysing the transformed host cells to isolate the recombinantly expressed protein a disulphide bond cleavage or reduction step is carried out with a disulphide bond cleavage agent. The present invention also relates to a composition isolated by such a method. The present invention also relates to the diagnostic and therapeutic application of these compositions.Type: ApplicationFiled: November 29, 2001Publication date: August 7, 2003Inventors: Geert Maertens, Fons Bosman, Marie-Ange Buyse