Methods for suppressing allergic reactions
Inventors
Finkelman, Fred D. • Khodoun, Marat V. • Krishnamurthy, Durga • Strait, Richard T. • Kucuk, Zeynep (Yesim)
Assignees
Medizinische Universitaet Wien • Cincinnati Childrens Hospital Medical Center • University of Cincinnati • US Department of Veterans Affairs
Publication Number
US-9868786-B2
Publication Date
2018-01-16
Expiration Date
2032-04-12
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Abstract
Provided are methods for suppressing IgE and IgG-mediated allergic reactions through monoclonal antibody applications. More specifically, methods are herein provided for safe induction of rapid desensitization. Specific embodiments are herein provided for suppressing allergic reactions in a subject, including specific methods of providing a monoclonal antibody selected from the group consisting of anti-FcεRIa and anti-FcγRIIb / RIII; administering the antibody to a subject at a dose that is lower than the level required to induce shock; and administering sequentially escalating doses of the monoclonal antibody so as to induce rapid desensitization to an allergen, thereby suppressing allergic reaction in the subject.
Core Innovation
The invention provides methods for suppressing IgE- and IgG-mediated allergic reactions by applying monoclonal antibodies. Specifically, it discloses methods for the safe induction of rapid desensitization to allergens through administration of monoclonal antibodies selected from anti-FcεRIα and anti-FcγRIIb/RIII.
The disclosed methods propose administering monoclonal antibodies at doses below levels that would induce shock, then giving sequentially escalating doses to induce rapid desensitization, thereby suppressing allergic reactions. The approach avoids direct allergen administration and offers a potentially safer and more effective alternative, particularly for individuals with high serum IgE levels or multi-antigen allergies.
Claims Coverage
The patent includes one independent claim covering a method of inducing rapid desensitization using monoclonal antibodies targeting specific Fc receptors. There are 17 inventive features detailing the specifics of this method and its administration protocol.
Use of monoclonal antibody for desensitization
A method of treating allergic disorders by inducing rapid desensitization using a monoclonal antibody selected from anti-FcεRIα and antibodies that specifically bind FcγRIIb and FcγRIII.
Administration at sub-shock inducing doses
Administering the monoclonal antibody at doses lower than levels that induce shock.
Sequentially escalating dosing regimen
Delivering 8 to 10 total doses within 24 hours with doses sequentially escalating, including doubling or tripling of each dose relative to the immediately preceding dose, administered every 1 to 3 hours.
Extended dosing with additional single doses
Providing additional single doses of the monoclonal antibody on every 2 to 3 days following the last escalating dose for about 8 to 22 days.
Use of dosing matching immunoglobulin half-life
Administering subsequent doses approximately 21 days after the last additional dose timed to match estimated IgG half-life.
Applicability to human subjects
The method is applicable to human subjects.
Treating food allergic reactions
Using the method for treating allergic reactions related to food allergens, including peanut allergy and proteins.
Combination with anti-CD4 monoclonal antibodies
Optionally administering anti-CD4 monoclonal antibodies in combination with the desensitization method.
Combination with antihistamines and corticosteroids
Administering antihistamines, corticosteroids, or both alongside the monoclonal antibody treatment to enhance safety and efficacy.
Broad allergen applicability
The allergen treated includes proteins, food, pollen, mold spores, dust, animal dander, insect debris, blood serum, drugs, cosmetics, and combinations thereof.
The claims cover methods of rapidly desensitizing allergic reactions using monoclonal antibodies targeting FcεRIα or FcγRIIb/RIII through controlled dosing regimens that are safe and applicable to various allergic disorders, including food allergies, optionally combined with other immunomodulatory agents.
Stated Advantages
Provides a safe induction of rapid desensitization to allergens without administering allergen directly, reducing risk especially in individuals allergic to multiple antigens.
Avoids severe anaphylactic reactions by administering sub-shock inducing doses and gradually escalating doses of monoclonal antibodies.
Potentially more effective in individuals with high serum IgE levels compared to treatments like omalizumab.
Longer lasting protection due to the long in vivo half-life of monoclonal antibodies compared to allergens.
Combination with antihistamines and corticosteroids further reduces risk of anaphylaxis during treatment.
The method allows for suppression of both IgE- and IgG-mediated allergic reactions by targeting specific Fc receptors on immune cells.
Documented Applications
Treatment of allergic disorders including food allergy, allergic rhinitis, asthma, atopic dermatitis, and anaphylaxis.
Suppression of IgE- and IgG-mediated immediate hypersensitivity reactions in subjects, including rapid desensitization to specific allergens.
Use in subjects allergic to multiple antigens where allergen-based rapid desensitization is risky.
Clinical use in humans for treatment of food allergies such as peanut allergy.
Potential adjunct therapy combined with anti-CD4 monoclonal antibodies, antihistamines, or corticosteroids to enhance safety and efficacy.
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