Combination therapies with anti-CD38 antibodies

Patent metadata

Field	Value
Publication number	US-9603927-B2
Application number	US-201514629941-A
Country	US
Kind code	B2
Filing date	Feb 24, 2015
Priority date	Feb 28, 2014
Publication date	Mar 28, 2017
Grant date	Mar 28, 2017

Abstract

The present invention relates to combination therapies with anti-CD38 antibodies.

First claim

The invention claimed is:

1. A method of treating a subject having a CD38-positive hematological malignancy, comprising administering to the subject in need thereof an anti-CD38 antibody in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), wherein the anti-CD38 antibody induces in vitro killing of CD38-expressing cells by antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement dependent cytotoxicity (CDC), apoptosis, or in vitro modulation of CD38 enzymatic activity and comprises heavy chain complementarity determining region (HCDR) 1 (HCDR1), 2 (HCDR2) and 3 (HCDR3) sequences of SEQ ID NOs: 6, 7 and 8, respectively, and light chain complementarity determining region (LCDR) 1 (LCDR1), 2 (LCDR2) and 3 (LCDR3) sequences of SEQ ID NOs: 9, 10 and 11, respectively, wherein the subject is resistant to or has acquired resistance to treatment with at least one chemotherapeutic agent.

2. The method of claim 1 , wherein the anti-CD38 antibody induces killing of the CD38-expressing cells by ADCC or CDC in vitro.

3. The method of claim 2 , wherein the anti-CD38 antibody is of IgG1, IgG2, IgG3 or IgG4 isotype.

4. The method of claim 3 , wherein the anti-CD38 antibody has a biantennary glycan structure with fucose content of about 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 14%, 13%, 12%, 11% 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1% or 0%.

5. The method of claim 3 , wherein the anti-CD38 antibody comprises a substitution in the antibody Fc at amino acid position 256, 290, 298, 312, 356, 330, 333, 334, 360, 378 or 430, wherein residue numbering is according to the EU index.

6. The method of claim 1 , wherein the anti-CD38 antibody comprises a heavy chain variable region (VH) of SEQ ID NO: 4 and a light chain variable region (VL) of SEQ ID NO: 5.

7. The method of claim 6 , wherein the anti-CD38 antibody comprises a heavy chain of SEQ ID NO: 12 and a light chain of SEQ ID NO: 13.

8. The method of claim 1 , wherein the CD38-positive hematological malignancy is multiple myeloma, acute lymphoblastic leukemia (ALL), non-Hodgkin's lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), Burkitt's lymphoma (BL), follicular lymphoma (FL) or mantle-cell lymphoma (MCL).

9. The method of claim 8 , wherein the CD38-positive hematological malignancy is DLBCL.

10. The method of claim 8 , wherein the subject is resistant to or has acquired resistance to treatment with a combination of at least one chemotherapeutic agent and an anti-CD20 antibody.

11. The method of claim 8 , wherein the subject has discontinued treatment with at least one chemotherapeutic agent or a combination of at least one chemotherapeutic agent and an anti-CD20 antibody due to side effects.

12. The method of claim 10 or 11 , wherein the anti-CD20 antibody is rituximab (RITUXAN®), ofatumumab (ARZERRA®), veltuzumab, ocrelizumab, obinutuzumab (GA-101), PRO13192 or ocratuzumab (AME-133v).

13. The method of claim 12 , wherein the anti-CD20 antibody is rituximab.

14. The method of claim 10 or 11 , wherein the at least one chemotherapeutic agent is cyclophosphamide, doxorubicin, vincristine, prednisone, ifosfamide, carboplatin or etoposide.

15. The method of claim 14 , wherein the at least one chemotherapeutic agent is a combination of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP).

16. The method of claim 14 , wherein the at least one chemotherapeutic agent is a combination of ifosfamide, carboplatin and etoposide (ICE).

17. The method of claim 1 , wherein the anti-CD38 antibody, cyclophosphamide, doxorubicin, vincristine and prednisone are administered simultaneously, sequentially or separately.

18. The method of claim 1 , wherein the patient is further treated with radiotherapy.

Assignees

• Janssen Biotech Inc

Inventors

• Doshi Parul

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title