Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1992-06-01
1997-12-02
Scheiner, Laurie A.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
4352523, 4352528, 4241841, 4241851, 4242751, 4242761, 536 231, 536 236, A61K 3936, C12N 1529
Patent
active
056934955
DESCRIPTION:
BRIEF SUMMARY
1. FIELD OF THE INVENTION
The invention provides recombinant DNA molecules which code for polypeptides, and the polypeptides per se, that have at least one epitope of an Aln g I pollen allergen, or a Cor a I pollen allergen or a Bet v I pollen allergen of a tree of the order Fagales, particularly alder, Alnus sp., or the entire Aln g I allergen protein, particularly hazel, Corylus sp., or the entire Cor a I allergen protein, or particularly birch, Betula sp., or the entire Bet v I allergen protein, and exhibit the same or similar anti-genicity as the Aln g I, the Cor a I or the Bet v I allergen. The invention also provides replicable microbial expression vehicles and microorganisms for use in processes for producing such allergenic polypeptides. Methods are provided for the diagnosis and therapy of allergic diseases using the synthetic polypeptides of the invention.
2.BACKGROUND OF THE INVENTION
It has long been known that a type I allergy to pollen proteins is associated with symptoms such as itchy and reddened eyes, running nose, swollen eyelids, coughing and asthmatic conditions. In this respect, the pollens of early-flowering trees of the order Fagales (e.g., birch, hazel, alder and hornbeam) hold an important position. Numerous studies have been carried out to identify and characterize the allergens of these pollens precisely (1-4). Progress with regard to the exact characterization of pollen allergens has been hindered by the heterogeneity of the pollen extracts currently in use. Some eight alIergens of alder pollen elicit an IgE response in atopics and one of them, Aln g I, a 17 kD protein, reacts with a majority of the sera of allergic patients as the major allergen (5, 6).
At least 10% of the population suffers from pollen allergies at various times and to varying extent. These allergies are mediated by IgE antibodies which react with pollen proteins. The possibility exists for a therapy for pollen allergies by hyposensitization, i.e., by the regular and slowly increasing administration of the proteins producing the allergy.
Diagnostic methods for allergic diseases, such as radio-allergosorbent test (RAST), paper radioimmunosorbent test (PRIST), enzyme-linked immunosorbent assay (ELISA), radioimmunoassays CRIA), immuno-radiometrie assays (IRMA), luminescence immunoassays (LIA), histamine release assays, and IgE immunoblots depend greatly upon the availability of pure nileteens. Protein extracts from pollen isolated from natural sources are difficult to standardize because preparations vary from batch to batch. For example, they may contain unwanted constituents, and/or certain proteins may be lost in the extraction procedure and be missing from the final preparation (7). Clearly, diagnostic tests which employ well defined allergens that can be reprodueibly prepared would be superior to tests which employ raw pollen extracts with an in. sufficiently defined mixture of allergens and other components. Recombinant DNA production of allergenic polypeptides, or altergenic fragments thereof, would allow more reproducible preparations of fliergens of defined content for standardized diagnostic and therapeutic methods.
Allergens may be purified to homogenity from pollen by known protein/chemical methods, for example, by means of affinity chromatography (8). These methods are relatively costly and require pollen as an expensive source for allergens. It would, therefor, be cheaper and more efficient to use recombinant DNA methods to produce an allergenic protein, or fragments of that protein.
Hyposensitization has proved to be an effective therapy in allergic diseases. This therapy consists of parenteraI or oral administration of allergens in increasing doses over a fairly long period of time.
3. SUMMARY OF THE INVENTION
The present invention provides recombinant DNA molecules which contain a nucleotide sequence that codes for a polypeptide which exhibits the same or similar antigenic properties as the major allergen, Aln g I, Cor a I or Bet v I of trees of the order Fagales, for example, of alder (Al
REFERENCES:
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Breitenbach Michael
Breiteneder Heimo
Kraft Dietrich
Rumpold Helmut
Scheiner Otto
Biomay Produktions- Und Handelsgesellschaft m.b.H.
Scheiner Laurie A.
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