Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Patent
1998-06-08
2000-03-21
Housel, James C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
435 71, 435 732, 4241991, 4242171, A61K 3902
Patent
active
060399597
DESCRIPTION:
BRIEF SUMMARY
The present invention concerns the prophylaxis, treatment and diagnosis of infections caused by Helicobacter pylori, together with methods for same.
Helicobacter pylori has recently been described as a cause of gastric ulcers, duodenal ulcers, gastric adenocarcinomas and atrophic gastritis (Lee, A. et al., 1993, Infect. Immun., 61: 1601-1610). Problems associated with it clinically are:
1. It is difficult to diagnose without an invasive biopsy, which has led to numerous attempts at a serological test, but there is no consensus of opinion as to which of these is best (Weiss, J. et al., 1994, J. Clin. Microbiol., 32: 1663-1668).
2. It is difficult to treat with conventional anti microbial chemotherapy (Czinn, S. J. et al., 1991, Infect. Immun., 39: 2359-2363) which has on that account been combined with anti-ulcer drugs such as Bismuth (Peterson, W. L., 1991, New England J. Med., 34: 1043-1048). The ulcers tend to recur, however.
It has been shown that antibody against urease (a key antigen) is a marker of infection (Nagata et al., 1992, Infect. Immun., 60: 4826-4831) and that one can vaccinate animals with urease and gain some protection (Lee, A. et al., supra. and Blanchard. T. G. et al., 1995, Infect. Immun., 63: 1394-1399).
Although the urease gene of H. pylori has been isolated and sequenced (Weiss. J. et al.. supra) and the protein encoded by the gene has also been sequenced key epitopes have not hitherto been identified.
The present invention provides agents for the detection of urease from H. pylori, and agents and epitopes for use in the treatment or diagnosis of infection due to H. pylori, as well as diagnostic tests and kits therefor and the use of the agents and epitopes in the manufacture of medicaments.
According to the present invention there is provided the use of an agent which binds specifically to an epitope selected from the group of LTPKELD (SEQ ID NO: 3) from ureA, and FISP (SEQ ID NO: 6), PTAF (SEQ ID NO: 13), EVGKVA (SEQ ID NO: 11) and SIP from ureB in a method of detection of urease from H. pylori, or a method of treatment or diagnosis of infection due to H. pylori.
Reference to epitopes is also reference to analogues thereof--to molecules which display the same epitope. Such molecules may, for example, be mimotopes (Geysen, H. M. et al., 1987, Journal of Immunological Methods, 102: 259-274) of the epitopes.
The agent may inhibit the (catalytic) activity of urease.
The agent may comprise an antibody or an antigen binding fragment thereof.
The antibody may be a whole antibody or an antigen binding fragment thereof and may in general belong to any immunoglobulin class. Thus, for example, it may be an immunoglobulin M antibody or an immunoglobulin G antibody. The antibody or fragment may be of animal, for example, mammalian origin and may be for example of murine, rat, sheep or human origin. It may be a natural antibody or a fragment thereof, or, if desired, a recombinant antibody fragment, i.e., an antibody or antibody fragment which has been produced using recombinant DNA techniques.
Particular recombinant antibodies or antibody fragments include, (1) those having an antigen binding site at least part of which is derived from a different antibody, for example those in which the hypervariable or complementarity determining regions of one antibody have been grafted into the variable framework regions of a second, different antibody (as described in, for example, European Patent Specification No 239400); (2) recombinant antibodies or fragments wherein non-Fv sequences have been substituted by non-Fv sequences from other, different antibodies (as described in, for example, European Patent Specification Nos 171469, 173494 and 194276); or (3) recombinant antibodies or fragments possessing substantially the structure of a natural immunoglobulin but wherein the hinge region has a different number of cysteine residues from that found in the natural immunoglobulin but wherein one or more cysteine residues in a surface pocket of the recombinant antibody or fragment is in the place of another ami
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Housel James C.
NeuTec Pharma plc
Portner Ginny Allen
LandOfFree
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