Anti-CD38 antibodies for treatment of acute lymphoblastic leukemia

Patent metadata

Field	Value
Publication number	US-9732154-B2
Application number	US-201514629965-A
Country	US
Kind code	B2
Filing date	Feb 24, 2015
Priority date	Feb 28, 2014
Publication date	Aug 15, 2017
Grant date	Aug 15, 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 acute lymphoblastic leukemia (ALL), comprising administering to the subject in need thereof an anti-CD38 antibody comprising heavy chain complementarity determining regions (HCDR) 1 (HCDR1), 2 (HCDR2) and 3 (HCDR3) sequences of SEQ ID NOs: 6, 7 and 8, respectively, and light chain complementarity determining regions (LCDR) 1 (LCDR1), 2 (LCDR2) and 3 (LCDR3) sequences of SEQ ID NOs: 9, 10 and 11, respectively, in combination with vincristine, wherein the subject is resistant or has acquired resistance to treatment with a BCR-ABL kinase inhibitor.

2. 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.

3. The method of claim 1 , wherein the anti-CD38 antibody induces in vitro killing of the ALL cells that express CD38 by antibody-dependent cell-mediated cytotoxicity (ADCC), complement dependent cytotoxicity (CDC), apoptosis, or in vitro modulation of CD38 enzymatic activity.

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

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

6. The method of claim 4 , wherein the anti-CD38 antibody comprises a substitution in the antibody Fc at amino acid positions 256, 290, 298, 312, 356, 330, 333, 334, 360, 378 or 430, wherein residue numbering is according to the EU index.

7. The method of claim 4 , 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 ALL is B-cell lineage ALL, T-cell lineage ALL, adult ALL or pediatric ALL.

9. The method of claim 8 , wherein the ALL is refractory or relapsed ALL.

10. The method of claim 8 , wherein the anti-CD38 antibody is administered as a remission induction or as postinduction therapy.

11. The method of claim 8 , wherein the subject has a white blood cell count of at least about 1×10 9 /L.

12. The method of claim 8 , wherein the ALL cells have a Philadelphia chromosome.

13. The method of claim 1 , wherein the BCR-ABL kinase inhibitor is imatinib, dasatinib, nilotinib, bosutinib, ponatinib, bafetinib, saracatinib, tozasertib danusertib or ibrutinib.

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

15. The method of claim 1 or 8 , wherein the subject is further treated or has been treated with radiotherapy.

16. The method of claim 1 or 8 , wherein the subject has received hematopoietic stem cell transplantation.

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

• A61P35/02

  specific for leukemia · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title

• A61K2039/55

  characterised by the host/recipient, e.g. newborn with maternal antibodies · CPC title