Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Reexamination Certificate
1997-09-26
2001-02-13
Saunders, David (Department: 1644)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
C435S069300, C435S091100, C530S350000, C536S023500
Reexamination Certificate
active
06187311
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a modified allergen, which is obtained by altering a major allergen (Der f II) of house dust mites by gene engineering, and to a method for production of the modified allergen. The modified allergen obtained by the production method can be utilized as a medicine for treating allergic diseases.
2. Description of the Related Art
It is considered that many allergic diseases are due to several kinds of symptoms which are developed by sensitization to the antigen causing the diseases, in which an IgE antibody specific for an allergen in blood serum and tissue is produced, and when the antibody is exposed again to the antigen, the antibody reacts with the antigen in each tissue. Particularly, an immediate type reaction is caused by the combination of antigens with IgE antibodies on mast cells and basophils followed by cross-linking the IgE antibodies, and the subsequent release of several kinds of chemical mediators from mast cells or basophils.
There is a method for controlling the binding between the antigen and the IgE antibody as a method for treating allergic diseases. If the binding between the antigen and the IgE antibody is controlled, the cross-linking among the IgE antibodies on mast cells or basophils, and the release of chemical mediators are controlled to have an effect on the treatment.
On the other hand, it appears that allergic diseases, such as bronchial asthma, childhood asthma, atopic dermatitis and the like, are mainly caused by an allergen from mites living in house dust. Several kinds of proteins of major mite allergens have been identified as major mite allergens (Platts-Mills et al., J. Allergy Clin. Immunol., 80, 755; 1987). Furthermore, a method for mass producing a purified major mite allergen has been disclosed (Yuuki et al., Japanese J. Allergology, 39, 557 (1990) and Japanese Patent Application No. 3-254683). In addition, the allergen in which a part of the above purified major mite allergen is changed, and a production method thereof has been filed (Japanese Patent Application No. 5-139793).
However, the proteins of the major allergens of mites which have been reported and identified show problems of an allergic reaction, namely anaphylactic shock, in hyposensitization therapy, because the activity of these allergens is high.
On the other hand, if the modified major mite allergen, which has lower IgE-binding activity or lower allergen activity than wild-type allergens and inhibits the binding of the antigen (Der f II) and the IgE antibody, is obtained, it is possible to provide an effective medicine for treating allergic diseases. The medicine does not show the anaphylactic shock of an allergic reaction caused by antigen administration, and it does not have an effect on the other parts of the immune system since the medicine is specific to the antigen. Modified major mite allergens have been disclosed in Japanese Patent Application Nos. 5-139793 and 5-275897. In the former application, there are problems of maintenance and stability of immunogenicity because the molecular structure is greatly changed by amino acid substitutions. In the latter application, it is not enough to minimize the structural change and to lower the allergen activity because a modified position of the allergen is not satisfactorily specified, and only alanine is used as a substitute amino acid.
SUMMARY OF THE INVENTION
The inventors of the present invention have found that, when an amino acid of a specified part of the major mite allergen Der f II, which is already disclosed, is replaced with other similar amino acids to minimize the structural change, it has been found that IgE-binding activity can be changed. It is found that there is no difference between the modified major mite allergens and those of a wild-type as to the activity that inhibits the antigen (Der f II) from binding to IgE.
An object of the present invention is to provide a method for mass producing the modified major mite allergen Der f II in which amino acid replacements are introduced by gene engineering. Namely, the present invention aims to produce a material which can be utilized as a medicine for treating allergic diseases.
The present invention involves a method in which a major allergen (Der f II) of house dust mites (
Dermatophagoides farinae
) is modified by gene engineering to replace amino acid residues with other amino acid residues, prokaryotic or eukaryotic host cells, transformed with a replication vector containing a gene which encodes the modified major mite allergen, Der f II, are cultured, and the modified major mite allergen is obtained from the culture.
REFERENCES:
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patent: 5773002 (1998-06-01), Thomas
patent: 5798099 (1998-08-01), Yuuki
patent: 5876722 (1999-03-01), Yuuki
patent: 06253851 (1994-09-01), None
patent: WO 92/04445 (1992-03-01), None
Yuuki, T. et al., Cloning and expression of cDNA for the major house dust mite allergen Der f ii inEscherichia coli,Agric. Biol. Chem. 55(5):1233-1238, 1991.
Trudinger, M., et al., cDNA encoding the major mite allergen Der f ii. Clin. Exp. Allerg. 21:33-37, 1991.
Yuuki, T., et al., Synthesis of biologically acitve recombinant Der f II. Int. Arch. Appl. Immunol. 94:354-356, 1991.
Naeve, CW., et al., Accuracy of automated DNA sequencing: a multi-laboratory comparison of sequencing results. Biotechniques. 19(3):448-453, 1995.
Nishiyama Chiharu
Okumura Yasushi
Yuuki Toshifumi
Asahi Breweries Ltd.
Browdy and Neimark
Saunders David
Tung Mary Beth
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