Antibodies to bone marrow stromal antigen 1

• US 9,175,092 B2
• Filed: 03/15/2013
• Issued: 11/03/2015
• Est. Priority Date: 06/28/2011
• Status: Active Grant

• Current Assignee: Oxford BioTherapeutics LTD
• Original Assignee: Oxford BioTherapeutics LTD
• Inventors: Rohlff, Christian, Terrett, Jonathan Alexander
• Primary Examiner(s): MERTZ, PREMA MARIA
• Application Number:
  US13/840,828
• Publication Number:
  US 20130273068A1
• Time in Patent Office: 963 Days
• Field of Search: 530/388.22
• US Class Current: 1/1
• 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. An isolated antibody or antigen binding fragment thereof that specifically binds to bone marrow stromal antigen 1 (BST1), said antibody or antigen binding fragment thereof comprising:

a) a heavy chain variable region comprising;

i) a first vhCDR comprising SEQ ID NO;

10;

ii) a second vhCDR comprising SEQ ID NO;

12 or SEQ ID NO;

51; and

iii) a third vhCDR comprising SEQ ID NO;

14; and

b) a light chain variable region comprising;

i) a first vlCDR comprising SEQ ID NO;

16;

ii) a second vlCDR comprising SEQ ID NO;

18; and

iii) a third vlCDR comprising SEQ ID NO;

20.

2. An antibody according to claim 1 comprising:

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

46 and

b) a light chain variable region comprising SEQ ID NO;

49.

3. The antibody or antigen-binding portion thereof, of claim 1, further comprising a covalently attached moiety.

4. The antibody or antigen-binding portion thereof, of claim 3, wherein said moiety is a drug selected from the group consisting of a maytansinoid, a dolastatin, an auristatin, a trichothecene, a calicheamicin, CC1065 and derivatives thereof.

6. An isolated monoclonal antibody, or an antigen binding portion thereof, which competes for binding to BST1 with an antibody set forth in claim 1 or 5.

7. The antibody of claim 1 or 5, wherein the antibody is of an IgG1 isotype.

5. An isolated antibody or antigen binding fragment thereof that specifically binds to bone marrow stromal antigen 1 (BST1), said antibody or antigen binding fragment thereof comprising:

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

2 and

b) a light chain variable region comprising SEQ ID NO;

4.

8. The antibody or antigen-binding portion thereof, of claim 5, further comprising a covalently attached moiety.

9. The antibody or antigen-binding portion thereof, of claim 8, wherein said moiety is a drug selected from the group consisting of a maytansinoid, a dolastatin, an auristatin, a trichothecene, a calicheamicin, CC1065 and derivatives thereof.

10. An isolated antibody or antigen binding fragment thereof that specifically binds to bone marrow stromal antigen 1 (BST1), wherein said antibody or antigen binding fragment thereof comprises heavy and light chain variable regions, and wherein the heavy chain variable region comprises SEQ ID NO:

2.

11. An isolated antibody or antigen binding fragment thereof that specifically binds to bone marrow stromal antigen 1 (BST1), wherein said antibody or antigen binding fragment thereof comprises heavy and light chain variable regions, and wherein the light chain variable region comprises SEQ ID NO:

4.

12. An isolated antibody or antigen binding fragment thereof that specifically binds to bone marrow stromal antigen 1 (BST1), wherein said antibody or antigen binding fragment thereof comprises heavy and light chain variable regions, and wherein the heavy chain variable region comprises SEQ ID NO:

46.

13. An isolated antibody or antigen binding fragment thereof that specifically binds to bone marrow stromal antigen 1 (BST1), wherein said antibody or antigen binding fragment thereof comprises heavy and light chain variable regions, and wherein the light chain variable region comprises SEQ ID NO:

49.

14. An isolated antibody or antigen binding fragment thereof that specifically binds to bone marrow stromal antigen 1 (BST1), wherein said antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising SEQ ID NO:

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

49.