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US-20260125488-A1 - Treatment Of IgE-Mediated Diseases With Antibodies That Specifically Bind CD38

US20260125488A1US 20260125488 A1US20260125488 A1US 20260125488A1US-20260125488-A1

Abstract

The present invention relates to treatment of IgE-mediated disease with antibodies that specifically bind CD38.

Inventors

  • Henny G. Otten

Assignees

  • UMC UTRECHT HOLDING B.V.

Dates

Publication Date
20260507
Application Date
20251230

Claims (20)

  1. 1 . A method of reducing an immunoglobulin type E (IgE) level in a subject in need thereof, comprising administering to the subject an antibody that specifically binds CD38 at about 5 mg/kg to about 25 mg/kg, wherein the antibody that specifically binds CD38 comprises a heavy chain variable region (VH) of SEQ ID NO: 4 and a light chain variable region (VL) of SEQ ID NO: 5.
  2. 2 . The method of claim 1 , wherein the antibody that specifically binds CD38 is an IgG1, IgG2, IgG3 or IgG4 isotype.
  3. 3 . The method of claim 1 , wherein the antibody that specifically binds CD38 is an IgG1 isotype.
  4. 4 . The method of claim 1 , wherein the antibody that specifically binds CD38 comprises a heavy chain of SEQ ID NO: 12 and a light chain of SEQ ID NO: 13.
  5. 5 . The method of claim 1 , wherein the antibody that specifically binds CD38 is daratumumab.
  6. 6 . The method of claim 1 , wherein the antibody that specifically binds CD38 is administered intravenously.
  7. 7 . The method of claim 1 , wherein the method reduces the IgE level in the subject by about 40% to about 90%.
  8. 8 . The method of claim 1 , wherein the method treats an IgE-mediated disease or reduces a risk of developing an IgE-mediated disease.
  9. 9 . The method of claim 8 , wherein the IgE-mediated disease is acute.
  10. 10 . The method of claim 8 , wherein the IgE-mediated disease is chronic.
  11. 11 . The method of claim 8 , wherein the IgE-mediated disease is allergic asthma, urticaria, angioedema, food allergy, an allergic response, atopic dermatitis, anaphylaxis, cutaneous mastocystosis, allergic rhinitis, nasal polyposis, Kimura's disease, eosinophilic otitis media, eosinophilic gastroenteritis, latex allergy, bronchopulmonary allergic aspergillosis, bullous pemphigoid, systemic lupus erythematosus, lupus, rheumatoid arthritis or an autoimmune disease.
  12. 12 . The method of claim 8 , wherein the IgE-mediated disease is an autoimmune disease.
  13. 13 . The method of claim 8 , wherein the IgE-mediated disease is an allergic response.
  14. 14 . The method of claim 8 , wherein the antibody that specifically binds CD38 is administered to the subject following an exposure to an allergen.
  15. 15 . The method of claim 8 , wherein the antibody that specifically binds CD38 is administered to the subject prophylactically to reduce the risk of developing the IgE-mediated disease.
  16. 16 . The method of claim 1 , wherein the antibody that specifically binds CD38 is administered with a second therapeutic agent.
  17. 17 . The method of claim 16 , wherein the second therapeutic agent is a standard of care treatment for an IgE-mediated disease.
  18. 18 . The method of claim 1 , wherein the antibody that specifically binds CD38 induces killing of IgE producing CD38 + cells.
  19. 19 . The method of claim 18 , wherein the antibody that specifically binds CD38 induces killing of IgE producing CD38 + cells by antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement dependent cytotoxicity (CDC), apoptosis, or modulation of CD38 enzymatic activity.
  20. 20 . The method of claim 19 , wherein the antibody that specifically binds CD38 induces killing of IgE producing CD38 + cells by ADCC.

Description

RELATED APPLICATIONS This application is a continuation of U.S. application Ser. No. 18/329,443, filed on Jun. 5, 2023, which is a continuation of U.S. application Ser. No. 16/312,133, filed on Dec. 20, 2018, now abandoned, which is the U.S. National Stage of International Application No. PCT/EP2017/066063, filed on Jun. 28, 2017, published in English, which claims the benefit of U.S. Provisional Application No. 62/355,526, filed on Jun. 28, 2016. The entire teachings of the above applications are incorporated herein by reference. INCORPORATION BY REFERENCE OF MATERIAL IN XML This application incorporates by reference the Sequence Listing contained in the following extensible Markup Language (XML) file being submitted concurrently herewith: File name: 01482021007.xml; created Dec. 17, 2025, 29,598 Bytes in size. FIELD OF THE INVENTION The present invention relates to treatment of IgE-mediated disease with antibodies that specifically bind CD38. BACKGROUND OF THE INVENTION A large and increasing proportion of the population in industrialized countries suffer from allergies. The current estimate for this debilitating condition is one in three people and a large proportion of this population is notably children. The pathogenesis of allergy is mediated by dysregulated triggering of IgE-mediated immune responses following repeated encounters with environmental antigens. IgE-mediated allergies are triggered by binding of IgE to the high affinity IgE receptor (FcERI), which is expressed on effector mast cells, basophils and activated eosinophils. As a result of these high affinity interactions, stable FcERI: IgE complexes are displayed on the surface of effector cells. Exposure to allergens leads to cross-linking and eventually clustering of IgE: FcERI complexes, thus triggering effector cell activation, degranulation and release of stored pro-allergenic mediators that leads to the initiation of an allergic response. Common environmental allergens which induce anaphylactic hypersensitivity are found in pollen, foods, house dust mites, animal danders, fungal spores and insect venoms. Atopic allergy is associated with anaphylactic hypersensitivity and includes the disorders, e.g., asthma, allergic rhinitis and conjunctivitis (hay fever), eczema, urticaria and food allergies. Further, an allergic reaction may lead to a dangerous life-threatening condition such as anaphylactic shock, which may be provoked by insect bites. For example, food allergy affects millions of people and is responsible for substantial morbidity, impaired quality of life and costs to the individual, family and society (Mills et al., Allergy 2007; 62:717-22. doi: 10.1111/j.1398-9995.2007.01425.x.). Recent studies estimate that the prevalence of food allergy in the general population is around 5% for adults and 8% for children (Sicherer et al., J Allergy Clin Immunol 2014; 133:291-307.e5. doi: 10.1016/j.jaci.2013.11.020.). The economic burden of food allergy in allergic children in the US are estimated $4184 per year per child (Gupta R et al., JAMA Pediatr 2013; 167:1026. doi: 10.1001/jamapediatrics.2013.2376). Allergic reactions can vary from mild symptoms limited to the oral cavity and skin, to severe respiratory and cardiovascular symptoms that can be potentially fatal. Emergency management of food allergic reactions includes administration of epinephrine, corticosteroids and antihistamines. With no curative treatment available, strict avoidance of the eliciting allergens is often necessary. Still, accidental ingestion occurs, often leading to hospital admission and treatment in an intensive care unit. In addition to allergies, IgE plays a role in autoimmune disorders contributing to their pathogenesis (Ettinger et al., Autoimmunity 50:25-35, 2017; Holgate, World Allergy Organization Journal 7:17, 2014). A need exists for treatment options for IgE-mediated diseases such as allergies and autoimmune diseases. SUMMARY OF THE INVENTION The invention provides for a method of treating an IgE-mediated disease, comprising administering to a subject in need thereof an antibody that specifically binds CD38 for a time sufficient to treat the IgE-mediated disease. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows that total IgE and timothy grass and house dust mite-specific IgE is reduced in a multiple myeloma patient treated with DARZALEX™ (daratumumab) over time. DETAILED DESCRIPTION OF THE INVENTION “CD38” refers to the human CD38 protein (synonyms: ADP-ribosyl cyclase 1, cADPr hydrolase 1, cyclic ADP-ribose hydrolase 1). Human CD38 has an amino acid sequence shown in GenBank accession number NP_001766 and in SEQ ID NO: 1. It is well known that CD38 is a single pass type II membrane protein with amino acid residues 1-21 representing the cytosolic domain, amino acid residues 22-42 representing the transmembrane domain, and residues 43-300 representing the extracellular domain of CD38. SEQ ID NO: 1MANCEFSPVSGDKPCCRLSRRAQLCLGVSILVLILVVVLA VVVPRWRQQWSGPGTTKRFP