Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1995-10-27
1999-08-17
Grimes, Eric
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
4352523, 43525411, 4353201, 435325, 536 235, C12N 510, C12N 1512, C12N 1563, C12P 2102
Patent
active
059392835
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
Approximately 10% of the population become hypersensitized (allergic) upon exposure to antigens from a variety of environmental sources. Those antigens that induce immediate and/or delayed types of hypersensitivity are known as allergens (King, T. P., (1976) Adv. Immunol., 23: 77-105. These include products of grasses, trees, weeds, animal dander, insects, food, drugs, and chemicals. Genetic predisposition of an individual is believed to play a role in the development of immediate allergenic responses (Young, R. P. et al., (1990) Clin. Sci., 79: 19a) such as atopy and anaphylaxis whose symptoms include hay fever, asthma, and hives.
The antibodies involved in atopic allergy belong primarily to the IgE class of immunoglobulins. IgE binds to basophils, mast cells and dendritic cells via a specific, high-affinity receptor Fc.epsilon.RI (Kinet, J. P., (1990) Curr. Opin. Immunol., 2: 499-505). Upon combination of an allergen acting as a ligand with its cognate receptor IgE, Fc.epsilon.RI bound to the IgE may be cross-linked on the cell surface, resulting in physiological manifestations of the IgE-allergen interaction. These physiological effects include the release of, among other substances, histamine, serotonin, heparin, chemotactic factor(s) for eosinophilic leukocytes and/or leukotrienes C4, D4, and E4, which cause prolonged constriction of bronchial smooth muscle cells (Hood, L. E. et al., Immunology (2nd ed.), The Benjamin/Cumming Publishing Co., Inc. (1984)). Hence, the ultimate consequence of the interaction of an allergen with IgE are allergic symptoms triggered by release of the aforementioned mediators. Such symptoms may be systemic or local in nature, depending on the route of entry of the antigen and the pattern of deposition of IgE on mast cells or basophils. Local manifestations generally occur on epithelial surfaces at the site of entry of the allergen. Systemic effects can induce anaphylaxis (anaphylactic shock) which results from IgE-basophil response to circulating (intravascular) antigen.
The pet dog (Canis familiaris) is kept in households the world over. In houses and public schools where dogs have been kept on a regular basis, dog dander allergens can be detected in dust samples (Wood, R. A. et al., (1988) Am Rev Respir. Dis., 137: 358-363, and Dybendal, T. et al., (1989) Allergy, 44: 401-411). The prevalence of allergy to dogs as assessed by skin prick test is approximately 15% (Haahtela, T. et al., (1981) Allergy, 36: 251-256, and de Groot, H. et al., (1991) J. Allergy Clin. Immunol., 87: 1056-1065). In one study, sensitivity to dog allergen(s) was detected in 40% of asthmatic children, even though dogs were not kept as pets in their homes (Vanto, T. and Koivikko, A., (1983) Acta Paediatr Scand., 72: 571-575).
Treatment of patients with dog allergy by administration of dog dander extracts has not proven to be as efficacious as treatment of cat allergic patients with cat dander extracts (Hedlin, G. et al.,(1991) J. Allergy Clin Immunol., 87: 955-964). As with any desensitization scheme involving injection of increasing doses of allergen(s), there are the drawbacks of potential anaphylaxis during treatment, and the possible necessity of continuing therapy over a period of several years to build up sufficient tolerance that results in significant diminution of clinical symptoms.
Dog hair and dander extracts are complex mixtures containing a number of allergenic proteins. (Loewenstein, H et al., (1982) Proceedings 11th International Congress of Allergology and Clinical Immunology, London, pp 545-548; Uchlin, T et al., (1984) Allergy, 39: 125-133; Yman, L. et al., (1984) Int. Arch. Allergy Appl. Immunol. U. 44: 358-368; Spitzauer, S. et al., (1993) Int. Arch. Allergy Immunol., 100: 60-67). Two allergens present in dog hair/dander have been purified using immunoaffinity chromatography. A major allergen from dog, Can f I (Nomenclature according to the criteria of the IUIS (Marsh, D. G. et al., (1988) Clin. Allergy, 18: 201-209; Ag13 according to original nomenclatur
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Bizinkauskas Christine B.
Brauer Andrew W.
Koniecsny Andrzej
Morgenstern Jay P.
Grimes Eric
Hanley Elizabeth A.
Immulogic Pharmaceutical Corporation
Mandragouras Amy E.
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