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

1 . A method of treating an IgE-mediated disease, comprising administering to a subject in need thereof a therapeutically effective amount of an antibody that specifically binds CD38 for a time sufficient to treat the IgE-mediated disease.

2 . The method of claim 1 , wherein the IgE-mediated disease is an allergic response to an allergen.

3 . The method of claim 2 , wherein the allergen is a pollen, a dust mite, a food allergen, a plant allergen, animal dander, insect stings, a fungus, a spore, a mold, latex, or a drug.

4 . The method of claim 1 , 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.

5 . The method of claim 1 , wherein the IgE-mediated disease is autoimmune disease.

6 . The method of claim 1 , wherein the IgE-mediated disease is lupus.

7 . The method of claim 6 , wherein lupus is systemic lupus erythematosus (SLE), discoid lupus erythematosus, subacute cutaneous lupus erythematosus, neonatal lupus or drug-induced lupus.

8 . The method of claim 1 , wherein the IgE-mediated disease is rheumatoid arthritis.

9 . The method of claim 1 , wherein the IgE-mediated disease is acute or chronic.

10 . The method of claim 1 , wherein the antibody that specifically binds CD38 is administered to the subject following exposure to an allergen.

11 . The method of claim 1 wherein the antibody that specifically binds CD38 competes for binding to CD38 with an antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 4 and a light chain variable region (VL) of SEQ ID NO: 5.

12 . The method of claim 1 , wherein the antibody that specifically binds CD38 comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2 and a HCDR3 amino acid sequences of SEQ ID NOs: 6, 7 and 8, respectively, and a light chain complementarity determining region 1 (LCDR1), a LCDR2 and a LCDR3 amino acid sequences of SEQ ID NOs: 9, 10 and 11, respectively.

13 . The method claim 1 , wherein the antibody that specifically binds CD38 comprises the VH having an amino acid sequence that is 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 4 and the VL having an amino acid sequence that is 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 5.

14 . The method of claim 1 , wherein the antibody that specifically binds CD38 is daratumumab or biosimilar thereof.

15 . The method of claim 1 , wherein the antibody that specifically binds CD38 is a non-agonistic antibody.

16 . The method of claim 1 , wherein the antibody that specifically binds CD38 comprises the VH of SEQ ID NO: 4 and the VL of SEQ ID NO: 5.

17 . The method of claim 1 , wherein the antibody that specifically binds CD38 comprises a heavy chain having an amino acid sequence that is 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 12 and a light chain having an amino acid sequence that is 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 13.

18 . The method of claim 1 , wherein the antibody that specifically binds CD38 comprises the heavy chain of SEQ ID NO: 12 and the light chain of SEQ ID NO: 13.

19 . The method of claim 1 , wherein the antibody that specifically binds CD38 comprises:

a. the VH of SEQ ID NO: 14 and the VL of SEQ ID NO: 15;

b. the VH of SEQ ID NO: 16 and the VL of SEQ ID NO: 17;

c. the VH of SEQ ID NO: 18 and the VL of SEQ ID NO: 19; or

d. the VH of SEQ ID NO: 20 and the VL of SEQ ID NO: 21.

20 . The method of claim 1 , wherein the antibody that specifically binds CD38 is an IgG1, IgG2, IgG3 or IgG4 isotype.

21 . The method of claim 1 , wherein the antibody that specifically binds CD38 induces killing of IgE producing CD38 + cells.

22 . The method of claim 21 , 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.

23 . The method of claim 22 , wherein the antibody that specifically binds CD38 induces killing of IgE producing CD38 + cells by ADCC.

24 . The method of claim 1 , wherein the antibody that specifically binds CD38 is administered to the subject prophylactically.

25 . The method of claim 1 , wherein the antibody that specifically binds CD38 is administered intravenously.

26 . The method of claim 1 , wherein the antibody that specifically binds CD38 is administered subcutaneously in a pharmaceutical composition comprising the antibody that specifically binds CD38 and a hyaluronidase.

27 . The method of claim 26 , wherein the hyaluronidase is rHuPH20 of SEQ ID NO: 22.

28 . The method of claim 1 , wherein the antibody that specifically binds CD38 is administered with a second therapeutic agent.

29 . The method of claim 28 , wherein the second therapeutic agent is a standard of care treatment for the IgE-mediated disease.

30 . The method of claim 28 , wherein the antibody that specifically binds CD38 and the second therapeutic agent are administered simultaneously, sequentially or separately.

31 . An antibody that specifically binds CD38 for use in the treatment of an IgE-mediated disease.

32 . The antibody of claim 31 for use in the treatment of an IgE-mediated disease, wherein the antibody comprises

a. the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 6, 7, 8, 9, 10 and 11;

b. the VH and the VL of SEQ ID NOs: 4 and 5, respectively;

c. the HC and the LC of SEQ ID NOs: 12 and 13, respectively; and/or

d. daratumumab or a biosimilar thereof.

33 . The antibody of claim 31 for use in the treatment of an IgE-mediated disease, wherein the IgE-mediated disease is an 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.

34 . A pharmaceutical composition for the treatment of an IgE-mediated disease comprising an antibody that specifically binds CD38.

35 . The pharmaceutical composition of claim 34 , wherein the antibody comprises

a. the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 6, 7, 8, 9, 10 and 11;

b. the VH and the VL of SEQ ID NOs: 4 and 5, respectively;

c. the HC and the LC of SEQ ID NOs: 12 and 13, respectively; and/or

d. daratumumab or biosimilar thereof.

36 . The pharmaceutical composition of claim 34 , wherein the IgE-mediated disease is an 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.