Methods of treating acute myeloid leukemia with antibodies to bone marrow stromal antigen 1

• US 9,732,160 B2
• Filed: 09/23/2015
• Issued: 08/15/2017
• Est. Priority Date: 06/28/2011
• Status: Active Grant

• Current Assignee: Oxford BioTherapeutics LTD
• Original Assignee: Oxford BioTherapeutics LTD
• Inventors: Terrett, Jonathan Alexander, Rohlff, Christian
• Primary Examiner(s): MERTZ, PREMA MARIA
• Application Number:
  US14/862,850
• Publication Number:
  US 20160002354A1
• Time in Patent Office: 692 Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 47/6871 the antibody targeting an enzyme
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/30 characterized by aspects of specificity or valency
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/77 Internalization into the cell

Abstract

The invention provides antibodies which bind to the ADP-ribosyl cyclase 2. Nucleic acid molecules encoding the antibodies, expression vectors, host cells and methods for expressing the antibodies are also provided. The antibodies may be used for the treatment of human cancers, including acute myeloid leukemia (AML), B-cell chronic lymphocytic leukemia, breast cancer, colorectal cancer, kidney cancer, head and neck cancer, lung cancer, ovarian cancer and pancreatic cancer and human inflammatory diseases, including asthma, gout, crohns, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, diabetes and atherosclerotic.

Claims

1. A method of treating acute myeloid leukemia (AML) in a patient comprising administering to the patient an antibody, or antigen binding portion thereof, wherein the antibody, or antigen binding portion thereof, comprises a heavy chain variable region CDR1 comprising SEQ ID NO:

10, a heavy chain variable region CDR2 comprising SEQ ID NO;

12 or SEQ ID NO;

51, a heavy chain variable region CDR3 comprising SEQ ID NO;

14, a light chain variable region CDR1 comprising SEQ ID NO;

16, a light chain variable region CDR2 comprising SEQ ID NO;

18, and a light chain variable region CDR3 comprising SEQ ID NO;

20.

4. The method of any one of claims 1-3, wherein the antibody, or antigen binding portion thereof, further comprises a covalently attached moiety.

5. The method of claim 4, wherein the moiety is a drug selected from the group consisting of a maytansinoid, a dolastatin, an auristatin, a trichothecene, a calicheamicin, CC 1065 and derivatives thereof.

6. The method of any one of claims 1-3, wherein the antibody, or antigen binding portion thereof:

(a) is internalized by a cell expressing BST1;

(b) induces antibody dependent cell-mediated cytotoxicity (ADCC);

(c) induces complement dependent cytotoxicity (CDC); and

/or

(d) induces T-cell cytotoxicity.

7. The method of any one of claims 1-3, wherein the antibody is of an IgG1 isotype.

2. A method of treating acute myeloid leukemia (AML) in a patient comprising administering to the patient an antibody, or antigen binding portion thereof, wherein the antibody, or antigen binding portion thereof, comprises:

(A) a heavy chain variable region comprising SEQ ID NO;

2 and/or a light chain variable region comprising SEQ ID NO;

4 or (B) an antibody, or an antigen binding portion thereof, which binds to the same epitope on BST1 as an antibody comprising a heavy chain variable region comprising SEQ ID NO;

2 and a light chain variable region comprising SEQ ID NO;

4.

3. A method of treating acute myeloid leukemia (AML) in a patient comprising administering to the patient an antibody, or antigen binding portion thereof, wherein the antibody, or antigen binding portion thereof, comprises (A) a heavy chain variable region comprising SEQ ID NO:

46 and/or a light chain variable region comprising SEQ ID NO;

49 or (B) an antibody, or an antigen binding portion thereof, which binds to the same epitope on BST1 as an antibody comprising a heavy chain variable region comprising SEQ ID NO;

46 and a light chain variable region comprising SEQ ID NO;

49.