Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage
Patent
1996-08-26
1998-02-10
Woodward, Michael P.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving virus or bacteriophage
530325, C12Q 170, C07K 700, C07K 1700
Patent
active
057167796
DESCRIPTION:
BRIEF SUMMARY
This application is the national stage of International Application no. PCT/SE94/01183, filed Dec. 8, 1994.
The present invention relates to a new peptide, to a new diagnostic antigen comprising said peptide and a method of in vitro diagnosing an active infection caused by hepatitis C virus (HCV) which makes use of a diagnostic antigen according to the invention.
BACKGROUND
The hepatitis C virus is one of the most recently identified human pathogenic viruses, first described in 1989 (Choo Q-L, et al., Science 244:359-362 (1989); Kuo G, et al., Science 244:362-364 (1989)). HCV is one of the first of the viruses termed non-A, non-B viruses to be identified. HCV seems to have been the major cause for post transfusional hepatitis since the introduction of HBV screening at blood banks (Kuo, et al., ibid). The world wide spread of HCV has been shown to be similar to that of HBV. Several routs for parenteral infections have been shown, such as needlestick injuries, intravenous drug use, and through immune globulin preparations (Cariani E, et al., Lancet 337:850 (1991); Chamot E, Aquired Immuno Deficiency Syndrome 6:430-431 (1992); Horst H. A., N Engl J Med 325:132-3 (1991)).
HCV has a size of 30-38 nm and is a member of the flaviviridae with a RNA coded genome of approximately 9.5 kilo bases. Based on the homology, the HCV genome has been proposed to code for two or three structural proteins, core and envelope, and perhaps also a matrix protein (Takamizawa A, et al., Journal of Virology 65:1105-13 (1991)).
The structure of the HCV is yet unknown, it can only be assumed by the proposed homology with the other members of the flaviviridae. Proteins related to HCV have only been produced as recombinant constructs, and no complete HCV virion has been observed. The proteins are estimated to be translated at the following sizes: core 192 amino acids; possibly the 70 carboxy terminal of these is the matrix protein, which is based on the homology with members of the flaviviridae (Takamizawa, et al., ibid); the E1 192 amino acids, the E2-NS1 344 amino acids, the NS2 278 amino acids, the NS3 609 amino acids, the NS4 398 amino acids, and the NS5 998 amino acids.
The most variable regions of the HCV genome have been shown to reside within the probable envelope genes, whereas the 5' end and the core regions of the HCV genome seem to be highly conserved.
The main assays, so far, for studying the immunology of HCV has both in Europe and USA been the enzyme immuno assay (EIA) with the recombinant C-100 construct which covers parts of the NS4 protein (Kuo, et al., ibid). More recently assays containing either long synthetic peptides or recombinant peptides which cover both structural and non-structural HCV products, have been introduced (Hosein B, et al., Proc Natl Acad Sci USA 88:3647-51 (1991); Mimms L, et al., Lancet 336:1590-1 (1990)). The problems with the early, first generation, assays were both unsatisfactory sensitivity and specificity (Dawson G. J., et al., Journal of Clinical Microbiology 29:551-556 (1991)), though the second generation assays do seem to have improved the serology according to these problems (Chaudhary R. K., et al., J Clin Lab Anal 7:164-7 (1993); Chaudhary R. K., et al., Journal of Clinical Microbiology 29:2329-2330 (1991); Marcellin P, et al., Lancet 337:551-2 (1991)).
What is known about the immune response to HCV has mainly been obtained by using these assays. Most persons infected by HCV develop antibodies to one or more of the proteins, mainly the core and NS3/NS4 (Nasoff M. S., et al., Proc Natl Acad Sci USA 88:5462-6 (1991); Okamoto H, et al., Virology 188:331-341 (1992); Okamoto H, et al., Japanese Journal of Experimental Medicine 60:223-33 (1990); Sallberg M, et al., Immunology Letters 33:27-34 (1992); Sallberg M, et al., Journal of Clinical Microbiology 30:1989-1994 (1992)). Recombinant constructs covering these regions are termed c22 (core; Chiba J, et al., Proc Natl Acad Sci 88:4641-4645 (1991); Harada S, Journal of Virology 65:3015-21 (1991)), c33 (part of NS3), and C-100 (parts of NS3
REFERENCES:
patent: 4816561 (1989-03-01), Todaro
patent: 5106726 (1992-04-01), Wang
Sallberg, et al., "Immune response to a single peptide containing an immunodominant region of hepatitis C virus C virus core protein: the isotypes and the recognition site", Immunology Letters, 33:27-34, 1992.
Takamizawa, et al., "Structure and Organization of the hepatitis C virus genome isolated from human carriers", Journal of Virology, 65:1105-1113, Mar. 1991.
Van Regenmortel, "The concept and operational definition of protein epitopes", Phil. Trans. R. Soc. Lond. B 323, 451-466, Jun. 12, 1989.
Sallberg Matti
Trojnar Jerzy
Brunback Brenda Glass
Euro-Diagnostic AB
Woodward Michael P.
LandOfFree
Diagnostic antigen and a method of in vitro diagnosing an active does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Diagnostic antigen and a method of in vitro diagnosing an active, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Diagnostic antigen and a method of in vitro diagnosing an active will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2076296