Combination therapies for heme malignancies with Anti-CD38 antibodies and survivin inhibitors

Patent metadata

Field	Value
Publication number	US-2016367663-A1
Application number	US-201615189577-A
Country	US
Kind code	A1
Filing date	Jun 22, 2016
Priority date	Jun 22, 2015
Publication date	Dec 22, 2016
Grant date	—

Abstract

The present invention relates to combination therapies for heme malignancies with anti-CD38 antibodies and survivin inhibitors.

First claim

We claim:

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 and a survivin inhibitor for a time sufficient to treat the CD38-positive hematological malignancy.

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

3 . The method of claim 1 , wherein the CD38-positive hematological malignancy is a plasma cell disease.

4 . The method of claim 3 , wherein the plasma cell disease is light chain amyloidosis (AL), multiple myeloma (MM) or Waldenstrom's macroglobulinemia.

5 . The method of claim 4 , wherein the plasma cell disease is MM.

6 . The method of claim 1 or 3 , wherein the anti-CD38 antibody 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.

7 . The method of claim 6 , wherein the anti-CD38 antibody binds to the region SKRNIQFSCKNIYR (SEQ ID NO: 2) and the region EKVQTLEAWVIHGG (SEQ ID NO: 3) of human CD38 (SEQ ID NO: 1).

8 . The method of claim 7 , wherein the anti-CD38 antibody comprises a heavy chain complementarity determining region (HCDR) 1, a HCDR2 and a HCDR3 sequences of SEQ ID NOs: 6, 7 and 8, respectively, and a light chain complementarity determining region (LCDR) 1, a LCDR2 and a LCDR3 sequences of SEQ ID NOs: 9, 10 and 11, respectively.

9 . The method of claim 8 , wherein the anti-CD38 antibody comprises the VH comprising an amino acid sequence that is 95%, 96%, 97%, 98%, 99% or 100% identical to that of SEQ ID NO: 4 and the VL comprising an amino acid sequence that is 95%, 96%, 97%, 98%, 99% or 100% identical to that of SEQ ID NO: 5.

10 . The method claim 9 , wherein the anti-CD38 antibody comprises the VH of SEQ ID NO: 4 and the VL of SEQ ID NO: 5.

11 . The method of claim 10 , wherein the anti-CD38 antibody is of IgG1, IgG2, IgG3 or IgG4 isotype.

12 . The method of claim 11 , wherein the anti-CD38 antibody is of IgG1 isotype.

13 . The method of claim 12 , wherein the anti-CD38 antibody induces CD38-positive cell killing by antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC) or apoptosis.

14 . The method of claim 1 or 3 , wherein the anti-CD38 antibody comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of:
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.

15 . The method of claim 14 , wherein the anti-CD38 antibody 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.

16 . The method of claim 1 , wherein the survivin inhibitor is a small molecule, a polynucleotide or a vaccine.

17 . The method of claim 16 , wherein the small molecule is YM155.

18 . The method of claim 1 , wherein the anti-CD38 antibody and the survivin inhibitor are administered simultaneously, sequentially or separately.

19 . The method of claim 18 , wherein the anti-CD38 antibody is administered intravenously.

20 . The method of claim 18 , wherein the anti-CD38 antibody is administered subcutaneously in a pharmaceutical composition comprising the anti-CD38 antibody and a hyaluronidase.

21 . The method of claim 20 , wherein the hyaluronidase is rHuPH20 of SEQ ID NO: 23 .

Assignees

• Janssen Biotech Inc

Inventors

• Doshi Parul
• Lokhorst Henk M
• Mutis Tuna

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• C07K16/2896

  against molecules with a "CD"-designation, not provided for elsewhere · CPC title