Methods for suppressing allergic reactions
Inventors
Finkelman, Fred D. • Khodoun, Marat V. • Morris, Suzanne C.
Assignees
Cincinnati Childrens Hospital Medical Center • University of Cincinnati • US Department of Veterans Affairs
Publication Number
US-10086005-B2
Publication Date
2018-10-02
Expiration Date
2032-04-12
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Abstract
A method of treating a subject suffering from an allergic disorder is provided, the method including inducing rapid desensitization to an allergen, the rapid desensitization effectuated by: administering to the subject a plurality of equal doses of a first anti-FcεRIα monoclonal antibody, wherein the plurality of equal doses are administered over a 6 to 8 hour period and wherein each dose is lower than a level required to induce shock, thereby inducing rapid desensitization to the allergen. Monoclonal antibodies and methods of co-administering or consecutively administering a combination thereof to effectuate rapid desensitization are also provided.
Core Innovation
The invention provides methods and monoclonal antibodies for inducing rapid desensitization to an allergen by administering repeated equal low doses of anti-FcεRIα monoclonal antibodies over a period of 6 to 8 hours. Each dose is lower than the level required to induce shock, thereby safely suppressing allergic reactions. This is contrasted with prior rapid desensitization techniques that rely on administration of allergens themselves and may be risky, especially in subjects allergic to multiple antigens.
The problem being solved addresses the limitations and risks of existing allergen desensitization therapies, including the challenges posed by multiple antigen allergies and the potential for severe reactions from allergen administration. Immediate hypersensitivity reactions caused by crosslinking of immunoglobulin Fc receptors on inflammatory cells lead to allergic disorders such as asthma and anaphylaxis. Current rapid desensitization methods using allergens over hours cannot fully suppress disease safely or rapidly, especially when serum antibodies neutralize allergens before reaching cell-bound IgE.
The innovation discovers that administration of multiple equal low doses of anti-FcεRIα monoclonal antibodies, such as IE7 and/or IB10, each below the shock-inducing threshold, can rapidly desensitize subjects to allergens. This method safely removes or blocks IgE on mast cells, reducing allergic reactions effectively in a time frame of hours. Co-administration or sequential administration of different anti-FcεRIα monoclonal antibodies targeting different epitopes enhances desensitization efficacy.
Claims Coverage
The patent includes 20 claims comprising method claims for rapid desensitization and claims to specific monoclonal antibodies. The independent claims focus principally on the method of rapid desensitization by administering repeated equal doses of an anti-FcεRIα monoclonal antibody and on the monoclonal antibodies IE7 and IB10 themselves.
Method of rapid desensitization using repeated equal low doses of a first anti-FcεRIα monoclonal antibody
A method of treating allergic disorders by administering multiple equal doses of a first anti-FcεRIα monoclonal antibody over a 6 to 8 hour period, each dose lower than that required to induce shock, thereby inducing rapid desensitization to an allergen.
Hourly administration of equal doses below shock threshold
The doses of the anti-FcεRIα antibody are administered hourly, where each dose is half or less than half the shock-inducing dose.
Use of specific anti-FcεRIα monoclonal antibodies IE7 and IB10
Employing monoclonal antibodies IE7, which binds human and rhesus monkey FcεRIα without competing with IgE, and IB10, which binds FcεRIα that is not IgE-associated, defined by specific heavy and light chain variable regions (SEQ ID NOs).
Desensitization to various allergen types
Application of the method to allergens including protein allergens, food allergens (peanut, tree nut, dairy), pollen, mold spores, dust, animal dander, insect debris, blood serum, drugs, and cosmetics.
Use of a second anti-FcεRIα monoclonal antibody in sequential or co-administration
Administering a second anti-FcεRIα monoclonal antibody following or together with the first, also in equal low doses below the shock threshold, for more effective rapid desensitization; co-administration involves 6 to 8 total doses, with the last 3 to 4 doses including both antibodies.
Monoclonal antibodies binding different epitopes of FcεRIα
The first and second anti-FcεRIα monoclonal antibodies bind to different epitopes on human or rhesus monkey FcεRIα, exemplified by IE7 and IB10.
Claims to monoclonal antibodies IE7 and IB10
Claims directed specifically to monoclonal antibody IE7 that binds human or rhesus monkey FcεRIα with defined variable regions, and antibody IB10 that binds FcεRIα not associated with IgE, with corresponding heavy and light chain variable region sequences.
The claims cover methods of safely inducing rapid desensitization to allergens through repeated administrations of equal doses of anti-FcεRIα monoclonal antibodies below shock-inducing levels, employing specific monoclonal antibodies IE7 and IB10 individually or in combination, targeting a broad spectrum of allergens.
Stated Advantages
Allows safe and effective rapid desensitization to allergens in hours using repeated low non-shock-inducing doses of anti-FcεRIα monoclonal antibodies.
Reduces risk compared to allergen-based rapid desensitization, particularly in subjects allergic to multiple antigens.
Effectively removes or blocks IgE on mast cells to suppress immediate hypersensitivity reactions.
Co-administration of two monoclonal antibodies targeting different FcεRIα epitopes enhances desensitization efficacy.
Documented Applications
Treatment of subjects suffering from allergic disorders including allergic rhinitis, asthma, atopic dermatitis, food allergies, and anaphylaxis.
Desensitization to allergens including food allergens such as peanut, tree nut, and dairy, as well as environmental allergens like pollen, mold spores, dust, animal dander, insect debris, blood serum, drugs, and cosmetics.
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