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  Novel peptide compositions and their use in particular in the preparation of pharmaceutical compositions active against the hepatitis c virusUSPTO Application #: 20070072176Title: Novel peptide compositions and their use in particular in the preparation of pharmaceutical compositions active against the hepatitis c virus Abstract: The invention relates to peptide compositions for use in the preparation of pharmaceutical compositions against hepatitis C virus, as well as corresponding methods. (end of abstract) Agent: Clark & Elbing LLP - Boston, MA, US Inventors: Genevieve Inchauspe, Anne Fournillier, Nourredine Himoudi, Perrine Martin USPTO Applicaton #: 20070072176 - Class: 435005000 (USPTO) Related Patent Categories: Chemistry: Molecular Biology And Microbiology, Measuring Or Testing Process Involving Enzymes Or Micro-organisms; Composition Or Test Strip Therefore; Processes Of Forming Such Composition Or Test Strip, Involving Virus Or Bacteriophage The Patent Description & Claims data below is from USPTO Patent Application 20070072176. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of, and claims priority from, U.S. Ser. No. 10/514,762, filed Nov. 16, 2004, which claims priority under 35 U.S.C. 371 from PCT/FR03/001478, filed May 15, 2003, which claims priority from French application no. 02/06111, filed May 17, 2002. The contents of each of the prior applications are incorporated herein by reference. [0002] A subject of the present invention is novel peptide compositions and their use in particular in the preparation of pharmaceutical compositions active against the hepatitis C virus. [0003] A subject of the present invention is a peptide composition useful in particular in prophylactic and therapeutic vaccination directed against the hepatitis C virus. [0004] Hepatitis C is the main cause of hepatitis acquired by transfusion. Hepatitis C can also be transmitted by other percutaneous routes, for example by injection of drugs by intravenous route. The risk of contamination to health professionals is moreover not negligible. [0005] Hepatitis C differs from the other forms of liver diseases associated with viruses, such as hepatitis A, B or D. Infections by the hepatitis C virus (HCV) are mostly chronic, resulting in liver diseases, such as hepatitis, cirrhosis and carcinoma in a large number of cases (5 to 20%). [0006] Although the risk of transmission of the virus by transfusion has diminished due to the establishment of screening tests in the 1990s, the frequency of hepatitis C remains high. By way of example, a recent study indicates that today there are still 10,000 to 15,000 new cases of infection per year in France (S. Deuffic et al., Hepatology 1999; 29: 1596-1601). At present, approximately 170 million people world-wide are chronically infected by HCV. Populations at high risk are chiefly hospital staff and intravenous-drug users, but asymptomatic blood donors exist who do not belong to these high-risk groups and in whom circulating anti-HCV antibodies have been found. For the latter, the infection route has not yet been identified. [0007] HCV was the first hepatotropic virus isolated by means of molecular biology techniques. The sequences of the viral genome were cloned before the viral particle was visualized. [0008] HCV belongs to a novel group of the Flaviviridae family, the hepaciviruses. This is a virus with a single positive RNA strand, of 9.5 kb, which is replicated by a copy of complementary RNA and the translation product of which is a precursor of a single polyprotein of approximately 3,000 amino acids. The 5' end of the HCV genome corresponds to a non-translated region adjacent to the genes which code for the structural proteins, the core protein of the nucleocapsid, the two envelope glycoproteins, E1 and E2, and a small protein called p7. The non-translated 5' region and the core gene are relatively well preserved in the different genotypes. The envelope proteins E1 and E2 are encoded by more variable regions from one isolate to another. The protein p7 is an extremely hydrophobic protein the function of which is not known. The 3' end of the HCV genome contains the genes which code for the non-structural proteins (NS2, NS3, NS4, NS5) and for a non-coding 3' region possessing a well-preserved domain (Major M E, Feinstone S M, Hepatology, June 1997, 25(6): 1527-1538). [0009] Therapy for the treatment of hepatitis C which is the current focus of attention is a dual therapy using pegylated interferon and ribavirin (Manns M P et al., The Lancet, 22 Sep. 2001, Vol. 358, 958-965). Whilst this therapy is particularly effective in the case of patients infected by viral strains belonging to genotypes 2 and 3, it only has a limited effect on genotypes 1a, 1b and 4 (Manns M P, above). [0010] It is therefore necessary to develop a vaccine composition targeting these poorly-responsive genotypes as a priority. [0011] Several studies today show that the control of an infection caused by HCV, either naturally ("spontaneous resolution"), or after treatment ("therapeutic resolution") is associated with the induction or potentialization of cell-mediated immune responses involving the T-CD4.sup.+ and T-CD8.sup.+ lymphocytes (CERNY A et al., J. Clin. Invest., 95: 521-530 (1995)). [0012] The object of vaccines based on the use of peptides is generally to induce immune responses mediated by the T-CD4+ and/or T-CD8+ lymphocytes. [0013] The molecules of the major histocompatibility complex (MHC) are described as class I or class II. Class I molecules are expressed on virtually all of the nucleated cells and can be the target of CD8.sup.+ cytotoxic T lymphocytes (CTLs). The CTLs recognize the peptides or epitopes which are presented in association with the MHC molecules of class I. [0014] For example, the class I molecule HLA-A2.1 indicates that the binding site of the peptide is created by bringing together the domains .alpha..sub.1 and .alpha..sub.2 of the heavy chain of class I (Bjorkman et al., Nature, 329: 506 (1987)). [0015] Certain authors have concluded the immunogenic power of peptide preparations on the basis of their good binding scores on HLA molecules, as in the Patent Application WO01/21189. [0016] Such a deduction is not evident and can lead: [0017] either to the selection of peptides having no immunogenic power, although having a high binding score, as demonstrated by the Applicant in Example 1 of the present Application with the FLAT peptide, [0018] or to the elimination of peptides which are in fact very immunogenic, as shown with the CIN peptide in Brinster C. et al. (Hepatology, Vol. 34, No 6, 2001, 1206-1217). In fact, although the CIN peptide has an average, or even low (335), binding score, it is nevertheless capable of inducing a strong response mediated by cytotoxic T lymphocytes. [0019] The Applicant has now unexpectedly found that a novel peptide composition containing at least two peptides chosen from the A to D peptides had a strong immunogenic power and had an effect on the ability of the cells originating from patients infected by viral strains of genotype 1a, 1b and 4 to induce specific immune responses. These patients preferably, but not limitatively, have an HLA of type HLA-A2.1. [0020] Thus, a subject of the present invention is the peptide compositions comprising at least two compounds chosen from: [0021] an A peptide having at least the following amino acid sequence SEQ ID NO: 1: [0022] X.sub.1AX.sub.2QGYKVX.sub.3VLNPSVX.sub.4ATLX.sub.5FGX.sub.6YMSKA- X.sub.7GX.sub.8, [0023] in which X.sub.1 is Y or H, X.sub.2 is A, G or T, X.sub.3 is R or L, X.sub.4 is A or T, X.sub.5 is G or S, X.sub.6 is A, T or V, X.sub.7 is H or Y and X.sub.8 is I, T, M or V, [0024] a B peptide having at least the following amino acid sequence SEQ ID NO: 45: GX.sub.18X.sub.19X.sub.20X.sub.21X.sub.22X.sub.23TSLTGRDX.sub.24NX.sub.25- X.sub.26X.sub.27GEX.sub.28QX.sub.29X.sub.30STAX.sub.31X.sub.32X.sub.33FLX.- sub.34X.sub.35X.sub.36X.sub.37NGX.sub.38X.sub.39WTVX.sub.40 [0025] in which X.sub.18 is L or V, X.sub.19 is L or F, X.sub.20 is G or S, X.sub.21 is C or T, X.sub.22 is I or V, X.sub.23 is I or V, X.sub.24 is K, R or T, X.sub.25 is Q or E, X.sub.26 is V or N, X.sub.27 is D, E or C, X.sub.28 is V or A, X.sub.29 is V, I, E or M, X.sub.30 is L or V, X.sub.31 is T, K or A, X.sub.32 is Q or H, X.sub.33 is S or T, X.sub.34 is A or G, X.sub.35 is T or S, X.sub.36 is C or A, X.sub.37 is V, I or T, X.sub.38 is V or A, X.sub.39 is C or M and X.sub.40 is Y or F, [0026] a C peptide having at least the following amino acid sequence SEQ ID NO: 127: [0027] SX.sub.47M X.sub.48FTX.sub.49X.sub.50X.sub.51TSPLX.sub.52X.sub.53X.sub.54X.sub.55TLX- .sub.56FNIX.sub.57GGWVAX.sub.58QX.sub.59 [0028] in which X.sub.47 is L or P, X.sub.48 is A or S, X.sub.49 is A or S, X.sub.50 is A or S, X.sub.51 is I or V, X.sub.52 is T, S or A, X.sub.53 is T or I, X.sub.54 is Q, S or G, X.sub.55 is N, Q, H, S, Y or T, X.sub.56 is L or M, X.sub.57 is L or W, X.sub.58 is A or S and X.sub.59 is L, P or I, and [0029] a D peptide having at least the following amino acid sequence SEQ ID NO: 174: [0030] X.sub.69KX.sub.70ARX.sub.71IVX.sub.72PX.sub.73LGX.sub.74RVCEKX.sub.- 75ALX.sub.76X.sub.77VX.sub.78X.sub.79X.sub.80X.sub.81 Continue reading... Full patent description for Novel peptide compositions and their use in particular in the preparation of pharmaceutical compositions active against the hepatitis c virus Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Novel peptide compositions and their use in particular in the preparation of pharmaceutical compositions active against the hepatitis c virus patent application. Patent Applications in related categories: 20080113340 - Diagnosis and treatment of cervical cancer - In certain aspects, the invention relates to methods of diagnosing cervical cancer by using a combination of certain biomarkers such as hTERT, IGFBP-3, transferrin receptor, beta-catenin, Myc-HPV E6 interaction, HPV E7, and telomere length. 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