Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Reexamination Certificate
1996-08-09
2003-12-16
Minnifield, N. M. (Department: 1645)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
C424S184100, C424S150100, C424S434000, C424S193100, C424S278100, C424S197110, C424S283100, C424S130100, C424S137100, C424S141100, C424S093400, C514S054000, C514S002600, C514S012200
Reexamination Certificate
active
06663873
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to an antigenic preparation and in particular to the use of this antigenic preparation for the treatment and prevention of gastroduodenal disease associated Helicobacter infection, particularly with
Helicobacter pylori
infection in humans.
BACKGROUND OF THE INVENTION
Helicobacter pylori
is a bacterium that infects the stomach lining of perhaps half the world's population. Infection with the organism is usually chronic, and results in continuing inflammation of the gastric mucosa. The infection is often asymptomatic. However, in association with other cofactors, a proportion of infected people go on to develop sequelae including peptic ulceration of the stomach or duodenum, gastric adenocarcinomas and lymphomas. Peptic ulcer treatment studies have shown that cure of
H. pylori
infection is associated with a dramatic reduction in the relapse rate of this usually chronic disease. Long term infection with
H. pylori
leads to the development of chronic atrophic gastritis, which has long been recognised as a precursor lesion in the development of gastric cancer. Thus a number of studies have now linked preceding
H. pylori
infection with an increased risk of developing gastric cancer. Therefore the treatment and prevention of
H. pylori
infection has the potential to prevent considerable mortality and morbidity from gastroduodenal disease.
There is no laboratory animal model of
H. pylori
infection suitable for use in screening new therapies and vaccines for
H. pylori
infection. However, a
Helicobacter felis
mouse model of gastric Helicobacter infection has been developed that has proved extremely useful in the screening new antimicrobial therapeutic regimens and vaccination protocols (Lee et al. 1990; Dick-Hegedus and Lee, 1991).
H. felis
is a spiral shaped bacterium that is very closely related to
H. pylori
. This bacterium colonises the stomach of mice in a very similar way to
H. pylori
in the human i.e. the main ecological niche is gastric mucus and colonisation is mainly seen in the antrum of the stomach. In germfree mice,
H. felis
infection induces a gastritis that is very similar to the human
H. pylori
infection with a chronic inflammation of mononuclear cells accompanied by a polymorphonuclear leucocyte infiltration. Infection with either organism results in the induction of a similar raised systemic humoral immune response against
H. pylori
and
H. felis
respectively (Lee et al., 1990).
The
H. felis
mouse model has proved to be very predictive of the efficacy of anti-
H. pylori
agents in humans. Thus, monotherapy with agents with high in vitro activity such as erythromycin show no significant in vivo effect against
H. felis
in mice, just as erythromycin has no anti-
H.pylori
effect in humans, despite its high antimicrobial effects in vitro. In contrast, the triple therapy regimens of a bismuth compound, metronidazole, and tetracycline or amoxycillin lead to a very high eradication rate in
H. felis
infected mice (Dick-Hegedus and Lee, 1991). Such triple therapies are the most successful human anti-
H. pylori
regimens, and at the present time are recommended as the first choice for anti-
H. pylori
therapy. The
H. felis
mouse model has also been used to demonstrate that mice can be orally immunised with Helicobacter antigen preparations of sonicated cells and cholera toxin adjuvant, to both treat active
H. felis
infection and to protect against
H. felis
infection, however the protective antigen or antigens in these preparations was not determined (see International Patent Application No. PCT/AU94/00416; Czinn et al., 1993).
In work leading to the present invention, a protective antigen of Helicobacter organisms has been identified, this antigen being recognised by monoclonal antibodies which are effective in treatment of
H. felis
-infected mice.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides an antigenic preparation for use in the treatment or prevention of Helicobacter infection, which comprises the lipopolysaccharide (LPS) of Helicobacter bacteria, or an immunogenic fragment thereof.
Preferably, the antigenic preparation comprises an at least partially purified LPS preparation.
The term “at least partially purified” as used herein denotes a preparation in which the LPS content is greater, preferably at least 30% and more preferably at least 50% greater, than the LPS content of a whole cell sonicate of Helicobacter bacteria. Preferably, the preparation is one in which the LPS is “substantially pure”, that is one in which the LPS content is at least 80%, more preferably at least 90%, of the total Helicobacter antigens in the preparation.
It is to be understood that the present invention extends not only to an antigenic preparation comprising the LPS of Helicobacter bacteria, but also to antigenic preparations comprising immunogenic fragments of this lipopolysaccharide, that is LPS fragments which are capable of eliciting a specific protective immune response in a mammalian host. Such immunogenic fragments may also be recognised by Helicobacter-specific monoclonal antibodies, particularly monoclonal antibodies which have a protective or therapeutic effect in relation to Helicobacter infection.
In another aspect, the present invention provides a vaccine composition for use in the treatment or prevention of Helicobacter infection in a mammalian host, which comprises an immunologically effective amount of an antigenic preparation as broadly described above, optionally in association with an adjuvant, together with one or more pharmaceutically acceptable carriers and/or diluents.
In yet another aspect, the present invention provides a method for the treatment or prevention of Helicobacter infection in a mammalian host, which comprises administration to said host of an immunologically effective amount of an antigenic preparation as broadly described above, optionally in association with an adjuvant.
In a related aspect, this invention provides the use of an immunologically effective amount of an antigenic preparation as broadly described above, optionally in association with an adjuvant, for the treatment or prevention of Helicobacter infection in a mammalian host.
In yet another aspect, the invention provides the use of an antigenic preparation as broadly described above, optionally in association with an adjuvant, in the manufacture of a vaccine composition for the treatment or prevention of Helicobacter infection in a mammalian host.
Preferably, but not essentially, the antigenic preparation of this invention is orally administered to the host, and is administered in association with a mucosal adjuvant. However, the invention also extends to parenteral administration of this antigenic preparation.
The present invention also extends to an antibody, particularly a monoclonal antibody, specific for the antigenic preparation as broadly described above, and in particular specific for the LPS of Helicobacter bacteria, including
H. felis
LPS and
H. pylori
LPS.
In this aspect, the invention further provides a method for the treatment or prevention of Helicobacter infection in a mammalian host, which comprises passive immunisation of said host by administration of an effective amount of an antibody, particularly a monoclonal antibody, specific for the antigenic preparation as broadly described above.
By use of the term “immunologically effective amount” herein in the context of treatment of Helicobacter infection, it is meant that the administration of that amount to an individual infected host, either in a single dose or as part of a series, is effective for treatment of Helicobacter infection. By the use of the term “immunologically effective amount” herein in the context of prevention of Helicobacter infection, it is meant that the administration of that amount to an individual host, either in a single dose or as part of a series, is effective to delay, inhibit or prevent Helicobacter infection. The effective amount varies depending upon the health and physical condi
Barr Ian George
Buck Fiona Jane
Doidge Christopher Vincent
Kleinig Michael John
Lee Adrian
CSL
Foley & Lardner
Minnifield N. M.
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