Subcutaneous administration of anti-CD38 antibodies

Patent metadata

Field	Value
Publication number	US-12371506-B2
Application number	US-201916961346-A
Country	US
Kind code	B2
Filing date	Jan 14, 2019
Priority date	Jan 12, 2018
Publication date	Jul 29, 2025
Grant date	Jul 29, 2025

Abstract

Methods of administering isolated anti-CD38 antibodies at low dosages subcutaneously are disclosed. The methods provide an effective treatment for autoimmune diseases and cancers, including hematologic diseases. Also disclosed are unit dosage forms for the anti-CD38 antibodies.

First claim

We claim:

1. A method for treating a disease in a human subject for which antibody binding to CD38 is indicated, the method comprising subcutaneously administering to the subject a unit dosage form of an isolated human anti-CD38 antibody, wherein the anti-CD38 antibody comprises a variable heavy (VH) chain region comprising a CDR1 having the amino acid sequence of SEQ ID NO:3, a CDR2 having the amino acid sequence of SEQ ID NO:4, and a CDR3 having the amino acid sequence of SEQ ID NO:5; and a variable light (VL) chain region comprising a CDR1 having the amino acid sequence of SEQ ID NO:6, a CDR2 having the amino acid sequence of SEQ ID NO:7 and a CDR3 having the amino acid sequence of SEQ ID NO:8, wherein the unit dosage form is in a volume of 1 mL or less, wherein the antibody is administered in a dosage of 0.3 milligram per kilogram body weight, wherein the disease is an autoimmune disease.

2. The method of claim 1 , wherein the VH chain region has the amino acid sequence of SEQ ID NO:9 and the VL chain region has the amino acid sequence of SEQ ID NO:10.

3. The method of claim 1 , wherein the anti-CD38 antibody comprises a heavy chain amino acid sequence of SEQ ID NO:11 and a light chain amino acid sequence of SEQ ID NO:12.

4. The method of claim 1 , wherein the unit dosage form is in a volume of 1 mL.

5. The method of claim 1 , wherein administering the anti-CD38 antibody does not cause hemolytic anemia or thrombocytopenia.

6. The method of claim 1 , wherein administering the anti-CD38 antibody results in less than 10%, less than 20%, less than 30%, less than 40%, or less than 50% incidence of grade 3 or 4 of one or more treatment-emergent adverse events (TEAEs) selected from the group consisting of anemia, hemolytic anemia, thrombocytopenia, fatigue, infusion-related reactions (IRRs), leukopenia, and lymphopenia.

7. The method of claim 1 , wherein administering the anti-CD38 antibody results in less than 10%, less than 20%, less than 30%, less than 40%, or less than 50% depletion of RBCs.

8. The method of claim 1 , wherein administering the anti-CD38 antibody results in less than 10%, less than 20%, less than 30%, less than 40%, or less than 50% depletion of platelets.

9. The method of claim 1 , wherein the disease is selected from the group consisting of autoimmune thrombocytopenia, immune mediated thrombocytopenia, idiopathic thrombocytopenia purpura, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), ulcerative colitis (UC), myasthenia gravis (MG), neuromyelitis optica (NMO), immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), anti-phospholipid syndrome (APS), pemphigus vulgaris (PV), pemphigus foliaceus (PF), anti-NMDAR encephalitis (NMDR), autoimmune hemolytic anemia (AIHA), Grave's disease, membranous nephropathy, Sjogren's syndrome (SS), ANCA vasculitis, epidermolysis bullosa acquisita (EBA), bullous pemphigoid (BP), Hashimoto's thyroiditis, scleroderma, IgG4-related disease, and graft-v-host disease.

10. The method of claim 1 , wherein the human anti-CD38 antibody is administered in the form of a pharmaceutically acceptable composition.

11. A unit dosage form comprising an isolated antibody that comprises a heavy chain variable region comprising SEQ ID NO:9 and a light chain variable region comprising SEQ ID NO:10, wherein the isolated antibody binds to CD38, wherein the unit dosage form is formulated for subcutaneous administration of the antibody in the treatment of a disease at a dosage of 0.3 milligram per kilogram body weight, wherein the unit dosage form is in a volume of 1 mL or less, wherein the disease is an autoimmune disease.

12. The unit dosage form of claim 11 , wherein isolated antibody comprises a heavy chain comprising SEQ ID NO:11 and a light chain comprising SEQ ID NO:12.

13. The unit dosage form of claim 11 , wherein the unit dosage form is in a volume of 1 mL.

14. The unit dosage form of claim 11 , wherein administering the anti-CD38 antibody does not cause hemolytic anemia or thrombocytopenia.

15. The unit dosage form of claim 11 , wherein administering the anti-CD38 antibody results in less than 10%, less than 20%, less than 30%, less than 40%, or less than 50% incidence of grade 3 or 4 of one or more treatment-emergent adverse events (TEAEs) selected from the group consisting of anemia, hemolytic anemia, thrombocytopenia, fatigue, infusion-related reactions (IRRs), leukopenia, and lymphopenia.

16. The unit dosage form of claim 11 , wherein administering the anti-CD38 antibody results in less than 10%, less than 20%, less than 30%, less than 40%, or less than 50% depletion of RBCs.

17. The unit dosage form of claim 11 , wherein administering the anti-CD38 antibody results in less than 10%, less than 20%, less than 30%, less than 40%, or less than 50% depletion of platelets.

18. The method of claim 1 , wherein subcutaneously administering the unit dosage form to the subject results in minimal or no reductions in total lymphocytes, B cells, T cells, cytotoxic T cells, helper T cells, monocytes, granulocytes, and platelets.

19. The unit dosage form of claim 11 , wherein subcutaneously administering the unit dosage form to the subject results in minimal or no reductions in total lymphocytes, B cells, T cells, cytotoxic T cells, helper T cells, monocytes, granulocytes, and platelets.

20. The unit dosage form of claim 11 , wherein the disease is selected from the group consisting of autoimmune thrombocytopenia, immune mediated thrombocytopenia, idiopathic thrombocytopenia purpura, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), ulcerative colitis (UC), myasthenia gravis (MG), neuromyelitis optica (NMO), immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), anti-phospholipid syndrome (APS), pemphigus vulgaris (PV), pemphigus foliaceus (PF), anti-NMDAR encephalitis (NMDR), autoimmune hemolytic anemia (AIHA), Grave's disease, membranous nephropathy, Sjogren's syndrome (SS), ANCA vasculitis, epidermolysis bullosa acquisita (EBA), bullous pemphigoid (BP), Hashimoto's thyroiditis, scleroderma, IgG4-related disease, and graft-v-host disease.

21. The unit dosage form of claim 11 , wherein the disease is immune thrombocytopenic purpura (ITP).

22. The unit dosage form of claim 11 , wherein the disease is rheumatoid arthritis (RA).

23. The unit dosage form of claim 11 , wherein the disease is systemic lupus erythematosus (SLE).

24. The method of claim 1 , wherein the disease is immune thrombocytopenic purpura (ITP).

25. The method of claim 1 , wherein the disease is rheumatoid arthritis (RA).

26. The method of claim 1 , wherein the disease is systemic lupus erythematosus (SLE).

27. A method for treating immune thrombocytopenic purpura (ITP) in a human subject, the method comprising subcutaneously administering to the subject a unit dosage form of an isolated human anti-CD38 antibody, wherein the anti-CD38 antibody comprises a heavy chain variable region comprising SEQ ID NO:9 and a light chain variable region comprising SEQ ID NO:10, wherein the unit dosage form is in a volume of 1 mL, wherein the antibody is administered in a dosage of 0.3 milligram per kilogram body weight.

Assignees

• Takeda Pharmaceuticals Co
• Dahl Martin
• Fedyk Eric
• Evans Robert
• Zhao Lin

Inventors

• Dahl Martin
• Fedyk Eric
• Evans Robert
• Zhao Lin

Classifications

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title