Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Allergen or component thereof
Reexamination Certificate
1999-07-29
2003-08-05
Chan, Christina (Department: 1644)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Allergen or component thereof
C424S282100, C530S324000, C530S350000
Reexamination Certificate
active
06602509
ABSTRACT:
This application claims Foreign Priority under 35 USC §119 (a-d) of EPO Application No. 98870167.8 filed Jul. 30, 1998.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is related to a new compound and a new method for the prevention and/or the treatment of allergy and/or diseases of allergic origin, particularly immediate hypersensitivity allergy.
2. Description of the Related Art
Immediate hypersensitivity is a form of allergic reaction which develops very quickly, namely within seconds or minutes of exposure of the patient to the causative allergen. This immediate reaction can be followed by a second reaction of delayed onset that can lead to inflammatory changes in the target organ and manifests itself by chronic symptoms such as asthma or atopic dermatitis.
Immediate hypersensitivity is mediated by antibodies belonging mainly, but not exclusively, to the IgE isotype. IgE antibodies bind to specific receptors on cells such as basophils, mastocytes or Langerhans' cells. Upon allergen exposure, surface-bound IgE transduce a signal into the cell, which is followed by cell activation, which in the case of basophils and mastocytes is accompanied by the release of preformed mediators such as histamine and enzymes, and the synthesis of metabolites of arachidonic acid. These mediators are responsible for the development of allergic signs and symptoms, such as bronchospasm, vasodilatation, hypersecretion of mucus and stimulation of sensory nerve ends resulting in pruritus.
IgE antibodies are produced by B lymphocytes that received appropriate activation signals. Full description of the mechanisms by which IgE antibodies are produced can be found in appropriate reviews (see for instance Vercelli D.,
Allergy Proc
. 14, pp. 413-416 (1993)).
Current treatment of allergic symptoms include allergen avoidance, drug therapy and immunotherapy. Complete avoidance from allergen exposure is the most logical approach, but it remains very difficult, or impossible to achieve in a vast majority of cases. Drug therapy is useful, but alleviates the symptoms without influencing their causes. In addition, drug treatment is usually limited by undesirable side-effects.
Current approaches for immunotherapy are:
1) conventional hyposensitisation which is a treatment consisting in administering to the patient progressively increasing doses of the allergen(s) to which he has developed a sensitivity;
2) allergen alteration aiming at reducing recognition by specific antibodies, IgE in particular;
3) allergen-derived peptides used to interfere in the cognate interaction between specific B and T cells or containing an IgE-binding B cell epitope.
Such allergen-derived peptides containing one or a few T cell epitope(s) used in animal experiments and in human beings in an attempt to inhibit specific T cell activation and induce a state of T cell unresponsiveness, are described in the patent application WO93/08279.
One human application of this concept is the administration of a peptide derived from the sequence of T cell epitopes present on the Fel dI allergen, by subcutaneous injections in cat-sensitive individuals (Wallner B. P., Gefter M. L.,
Allergy
49, pp. 302-308 (1994)). An alternative, complementary approach of this concept has also been used in animal experiments. The peptides used are modified in such a manner as to keep the ability to bind to MHC-class II determinants on specific B cells, but which have lost their capacity to activate the corresponding T cells (O'Hehir R. E. et al.,
International Immunology
3, pp. 819-826 (1991)).
It is known that allergic reactions are generated by the liberation of mediators from target cells, such as basophils or mastocytes, having high-affinity surface receptors for IgE, which are occupied by IgE antibodies. The minimum requirement for mediator liberation to occur is that two IgE molecules recognising the same allergen are cross-linked, which in turn cross-link the receptor, resulting in the transduction of an activating signal within the cell. If only one IgE molecule is able to bind the allergen, no cell activation ensues, but the binding site of the IgE would be occupied, preventing cell activation upon exposure to native allergen. The use of a single IGE-binding epitope has therefore been claimed to be a suitable approach for the treatment of allergic diseases (Ball T. et al., J. Biol. Chem. 269, pp. 28323-28328 (1994), EP-A-0714662).
U.S. Pat. No. 4,946,945 describes a protein conjugate useful in immunotherapy, composed of a biological response modifier (BRM) and an allergen. Said conjugate could be combined with a pharmaceutically acceptable carrier. Cytokin, bacterial, fungal and viral immunopotentiators and thymus hormones are disclosed as suitable BRMs for use in said document.
The patent application WO95/31480 describes the preparation and the use of a synthetic compound made of two alpha-helices with specific arrangements of various amino acids. Said compound is used as a support for the binding of functional units, especially epitopes B and/or T.
It is meant by “atopy”, a predisposition, partly of genetic origin, of an individual having an immune system producing an excess of antibodies belonging to the IgE isotype in response to exposure to allergens. Individuals presenting such characteristics are therefore called “atopics”.
An “allergen” is defined as a substance, usually a macromolecule of proteic composition, which elicits the production of IgE antibodies in predisposed, preferably genetically disposed, individuals (atopics).
Similar definitions are presented in the following references:
Clin. Exp. Allergy
, No. 26, pp. 494-516 (1996);
Mol. Biol. of Allergy and Immunology
, ed. R. Bush,
Immunology and Allergy Clinics of North American Series
(August 1996).
These allergens are preferably the main allergens which are selected from the group consisting of:
food allergens present in peanuts, codfish, egg white, soybean, shrimp, milk and wheat,
house dust mites allergens obtained from Dermatophagoides spp. pteronyssinus, farinae and microceras,
Euroglyphus maynei
or Blomia,
allergens from insects present in cockroach or hymenoptera,
allergens from pollen, especially pollens of tree, grass and weed,
allergens present in animals, especially in cat, dog, horse and rodent,
allergens present in fungus, especially from Aspergillus, Alternaria or Cladosporium, and
occupational allergens present in such products as latex, amylase, etc.
Said allergens can also be main allergens present in moulds or various drugs such as hormones, antibiotics, enzymes, etc.
“Allergy” is the ensemble of signs and symptoms which are observed whenever an atopic individual encounters an allergen to which he has been sensitised, which may result in the development of various diseases and symptoms such as allergic rhinitis, bronchial asthma, atopic dermatitis, etc.
“Hypersensitivity” is an untoward reaction produced in a susceptible individual upon exposure to an antigen to which he has become sensitised; immediate hypersensitivity depends of the production of IgE antibodies and is therefore equal to allergy.
It is meant by the terms “epitope” or “antigenic determinant”, one or several portions (which may define a conformational epitope) of an antigen (structure of a macromolecule, including an allergen, preferably made of proteic composition but also made of one or more hapten(s) or portion of a pharmaceutical active compound) which are specifically recognised and bound by an antibody or a receptor at the cell surface of a B or T lymphocyte.
SUMMARY OF THE INVENTION
The purpose of the present invention is to provide a vaccination strategy by which the antibody response made by atopic individuals against allergens is deviated from the allergen major determinants that are spontaneously recognised by atopic individuals, to determinants on the same molecule that are spontaneously recognised by antibodies of non-atopic individuals, or to determinants which are not spontaneously recognised by the majority of individuals, independently of their
Jacquemin Marc
Saint-Remy Jean-Marie
Chan Christina
Huynh Phuong N.
Leuven Research & Development VZW
Wenderoth , Lind & Ponack, L.L.P.
LandOfFree
Compound and method for the prevention and/or the treatment... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compound and method for the prevention and/or the treatment..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compound and method for the prevention and/or the treatment... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3114142