Antibodies against a proliferating inducing ligand (APRIL) and methods of use thereof

1. An isolated antibody or antibody fragment which binds to human a proliferating inducing ligand (APRIL) comprising:

a. an antibody heavy chain variable region comprising CDRs SEQ ID NOs: 9, 10, and 11; and

b. an antibody light chain variable region comprising CDRs SEQ ID NOs: 12, 13, and 14,

wherein the antibody or antibody fragment fully blocks the binding of APRIL with human transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and human B cell maturation antigen (BCMA).

2. The isolated antibody or antibody fragment of claim 1 comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 5 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 6.

3. The isolated antibody or antibody fragment of claim 1 or 2 , wherein the antibody or antibody fragment:

(a.) binds human APRIL with a K D of about 10 nM or about 10 −8 to 10 −11 M; and

(b.) blocks binding of human TACI and human BCMA to human APRIL with an IC 50 of about 2 nM or lower.

4. An isolated antibody or antibody fragment which binds to human APRIL wherein the antibody or antibody fragment binds to an epitope having the amino acid sequence of SEQ ID NO:33 or SEQ ID NO:34.

5. An antibody or antibody fragment which competes for a binding epitope on human APRIL with the antibody or antibody fragment of claim 2 , and:

(a.) binds human APRIL with a K D of about 10 nM or about 10 −8 to 10 −11 M;

(b.) binds to human APRIL with about the same K D as an antibody having a heavy chain comprising the amino acid sequence of SEQ ID NO: 5 and a light chain comprising the amino acid sequence of SEQ ID NO: 6; or

c. blocks binding of human TACI and human BCMA to human APRIL with an IC 50 of about 2 nM or lower.

6. The isolated antibody or antibody fragment of claim 1 , 4 or 5 , wherein the antibody or antibody fragment is:

(a.) a chimeric antibody or an antibody fragment thereof;

(b.) a human antibody or an antibody fragment thereof;

(c.) a humanized antibody or an antibody fragment thereof; or

(d.) an antibody fragment selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, scFv, F(ab′) 2 , bispecific mAb and a diabody.

7. The isolated antibody or antibody fragment of claim 1 , 4 or 5 wherein the antibody or antibody fragment inhibits the proliferation and survival of B-cells.

8. A composition comprising the isolated antibody or antibody fragment of claim 1 , 4 or 5 in combination with a pharmaceutically acceptable carrier or diluent.

9. A method for treating an APRIL-dependent condition comprising administering an effective amount of the isolated antibody or antibody fragment of claim 1 , 4 or 5 wherein the APRIL dependent condition is selected from the group consisting of APRIL-dependent cancers, APRIL-dependent inflammatory diseases or APRIL-dependent auto-immunity.

10. The method of claim 9 wherein the APRIL-dependent cancer is a B cell malignancies, a Non-Hodgkin's lymphoma and diffuse large B cell lymphoma, or an APRIL-dependent solid tumor.

11. The method of claim 9 , wherein the cancer is selected from the group consisting of Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma, Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B cell lymphoma and a glioblastoma.

12. The method of claim 7 wherein the inflammatory disease is selected from the group consisting of Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) and Sjogren's syndrome or Multiple Sclerosis.

13. A method for inhibiting immune cell proliferation and/or survival comprising administrating an effective amount of the isolated antibody or antibody fragment of claim 1 , 4 or 5 .

14. A diagnostic assay for detecting expression of human APRIL in cells, tissues or serum by labeling the isolated antibody or antibody fragment of claim 1 , 4 or 5 and detecting binding of the labelled isolated antibody or antibody fragment in the cells, tissues or serum.