Anti-CD38 Antibodies for Treatment of Acute Lymphoblastic Leukemia

Patent metadata

Field	Value
Publication number	US-2017320961-A1
Application number	US-201715651333-A
Country	US
Kind code	A1
Filing date	Jul 17, 2017
Priority date	Feb 28, 2014
Publication date	Nov 9, 2017
Grant date	—

Abstract

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

First claim

1 . A method of treating a subject having acute lymphoblastic leukemia (ALL), comprising administering to a patient in need thereof an anti-CD38 antibody that 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, wherein the anti-CD38 antibody induces in vitro killing of ALL 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.

2 . The method of claim 1 , 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).

3 . The method of claim 2 , wherein the anti-CD38 antibody induces in vitro killing of the ALL cells that express CD38 by ADCC or CDC.

4 . The method of claim 1 , 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 antibodies comprise 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 1 , wherein the anti-CD38 antibody comprises the heavy chain complementarity determining regions (HCDR) 1 (HCDR1), 2 (HCDR2) and 3 (HCDR3) sequences of SEQ ID NOs: 6, 7 and 8, respectively.

8 . The method of claim 7 , wherein the anti-CD38 antibody comprises the light chain complementarity determining regions (LCDR) 1 (LCDR1), 2 (LCDR2) and 3 (LCDR3) sequences of SEQ ID NOs: 9, 10 and 11, respectively.

9 . The method of claim 8 , wherein the anti-CD38 antibody comprises the heavy chain variable region (VH) of SEQ ID NO: 4 and the light chain variable region (VL) of SEQ ID NO: 5.

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

11 . The method of claim 10 , wherein the anti-CD38 antibody comprises the heavy chain of SEQ ID NO: 12 and the light chain of SEQ ID NO: 13.

12 . The method of claim 1 , wherein the ALL is B-cell lineage ALL, T-cell lineage ALL, adult ALL or pediatric ALL.

13 . The method of claim 12 , wherein the ALL is refractory or relapsed ALL.

14 . The method of claim 12 , wherein the anti-CD38 antibody is administered as a remission induction or as postinduction therapy.

15 . The method of claim 12 , wherein the subject has a white blood cell count of at least about 1×10 9 /L.

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

17 . The method of claim 12 , wherein the subject is resistant or has acquired resistance to treatment with a BCR-ABL kinase inhibitor.

18 . The method of claim 17 , wherein the BCR-ABL kinase inhibitor is imatinib, dasatinib, nilotinib, bosutinib, ponatinib, bafetinib, saracatinib, tozasertib danusertib or ibrutinib.

19 . The method of claim 1 or 12 , wherein the anti-CD38 antibody is administered in combination with vincristine.

20 . The method of claim 19 , wherein the anti-CD38 antibody and vincristine are administered simultaneously, sequentially or separately.

21 . The method of claim 1 or 12 , wherein the subject is further treated or has been treated with radiotherapy.

22 . The method of claim 1 or 12 , wherein the subject has received hematopoietic stem cell transplantation.

Assignees

• Janssen Biotech Inc

Inventors

• Doshi Parul

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P43/00

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

• C07K2317/734

  Complement-dependent cytotoxicity [CDC] · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• C07K16/2896 Primary

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