Antibody molecules to april and uses thereof

Abstract

Antibody molecules that specifically bind to APRIL are disclosed. The antibody molecules can be used to treat, prevent, and/or diagnose disorders, such as IgA nephropathy.

What is claimed is: 
     
         1 . An anti-APRIL antibody molecule, which:
 (i) binds, or substantially binds, to human APRIL;   (ii) binds, or substantially binds, to mouse APRIL;   (iii) inhibits, or substantially inhibits, binding of APRIL to TACI; and   (iv) inhibits, or substantially inhibits, binding of APRIL to BCMA.   
     
     
         2 . The antibody molecule of  claim 1 , which binds, or substantially binds, to human APRIL at an EC 50  of 20 nM or less, 10 nM or less, 9 nM or less, 8 nM or less, 7 nM or less, 6 nM or less, 5 nM or less, 4 nM or less, 3 nM or less, 2 nM or less, 1 nM or less, 0.8 nM or less, 0.6 nM or less, 0.4 nM or less, 0.2 nM or less, 0.1 nM or less, 0.05 nM or less, 0.02 nM or less, 0.01 nM or less, 0.005 nM or less, 0.002 nM or less, 0.001 nM or less, between 0.001 nM and 20 nM, between 0.01 nM and 20 nM, between 0.1 nM and 20 nM, between 0.1 nM and 10 nM, between 0.5 nM and 5 nM, between 1 nM and 5 nM, between 0.001 nM and 0.1 nM, between 0.001 nM and 0.01 nM, between 0.001 nM and 0.005 nM, between 0.01 nM and 0.05 nM, or between 0.01 nM and 0.1 nM. 
     
     
         3 . The antibody molecule of  claim 1 , which binds, or substantially binds, to mouse APRIL at an EC 50  of 100 nM or less, 80 nM or less, 60 nM or less, 40 nM or less, 20 nM or less, 10 nM or less, 9 nM or less 9 nM or less, 8 nM or less, 7 nM or less, 6 nM or less, 5 nM or less, 4 nM or less, 3 nM or less, 2 nM or less, 1 nM or less, 0.8 nM or less, 0.6 nM or less, 0.4 nM or less, 0.2 nM or less, 0.1 nM or less, 0.05 nM or less, 0.02 nM or less, 0.01 nM or less, 0.005 nM or less, 0.002 nM or less, or 0.001 nM or less, between 0.001 nM and 100 nM, between 0.001 nM and 50 nM, between 0.01 nM and 20 nM, between 0.1 nM and 10 nM, between 0.5 nM and 5 nM or between 1 nM and 5 nM, between 0.001 nM and 0.1 nM, between 0.001 nM and 0.01 nM, between 0.001 nM and 0.005 nM, between 0.01 nM and 0.05 nM, or between 0.01 nM and 0.1 nM. 
     
     
         4 . The antibody molecule of  claim 1 , which inhibits, or substantially inhibits, binding of APRIL to TACI at an IC 50  of 50 nM or less, 40 nM or less, 30 nM or less, 20 nM or less, 10 nM or less, 9 nM or less, 8 nM or less, 7 nM or less, 6 nM or less, 5 nM or less, 4 nM or less, 3 nM or less, 2 nM or less, 1 nM or less, 0.8 nM or less, 0.6 nM or less, 0.4 nM or less, 0.2 nM or less, 0.1 nM or less, 0.05 nM or less, 0.002 nM or less, or 0.001 nM or less, between 0.001 nM and 50 nM, between 0.01 nM and 50 nM, between 0.1 nM and 50 nM, between 0.1 nM and 25 nM, between 0.1 nM and 10 nM, between 0.5 nM and 5 nM, between 1 nM and 5 nM, between 0.001 nM and 0.1 nM, between 0.001 nM and 0.01 nM, between 0.001 nM and 0.005 nM, between 0.01 nM and 0.05 nM, or between 0.01 nM and 0.1 nM. 
     
     
         5 . The antibody molecule of  claim 1 , which inhibits, or substantially inhibits, binding of APRIL to BCMA at an IC 50  of 200 nM or less, 150 nM or less, 100 nM or less, 50 nM or less, 40 nM or less, 30 nM or less, 20 nM or less, 10 nM or less, 9 nM or less, 8 nM or less, 7 nM or less, 6 nM or less, 5 nM or less, 4 nM or less, 3 nM or less, 2 nM or less, 1 nM or less, 0.8 nM or less, 0.6 nM or less, 0.4 nM or less, 0.2 nM or less, 0.1 nM or less, 0.05 nM or less, 0.02 nM or less, 0.01 nM or less, 0.005 nM or less, 0.002 nM or less, or 0.001 nM or less, between 0.001 nM and 100 nM, between 0.001 nM and 50 nM, between 0.01 nM and 20 nM, between 0.1 nM and 10 nM, between 0.5 nM and 5 nM or between 1 nM and 5 nM, between 0.001 nM and 0.1 nM, between 0.001 nM and 0.01 nM, between 0.001 nM and 0.005 nM, between 0.01 nM and 0.05 nM, or between 0.01 nM and 0.1 nM. 
     
     
         6 . The antibody molecule of  claim 1 , wherein binding of the antibody molecule to APRIL inhibits, or substantially inhibits, the binding of the CRD2 domain of TACI to APRIL. 
     
     
         7 . The antibody molecule of  claim 1 , wherein binding of the antibody molecule to human APRIL, inhibits, or substantially inhibits, the binding of human TACI, to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more, of the human APRIL residues from any of Tables 3-4 or 7-8. 
     
     
         8 . The antibody molecule of  claim 1 , which comprises one or both of:
 (i) a heavy chain variable region (VH) comprising one, two, or all of the following:   an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the HCDR1 of a monoclonal antibody chosen from antibodies 3525, 3530, 3833, 3631, 3732, 4540, 4540-063, or 4540-033;   an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the HCDR2 of the monoclonal antibody; or   an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the HCDR3 of the monoclonal antibody, or   (ii) a light chain variable region (VL) comprising one, two, or all of the following:   an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the LCDR1 of the monoclonal antibody;   an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the LCDR2 of the monoclonal antibody; or   an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the LCDR3 of the monoclonal antibody.   
     
     
         9 . The antibody molecule of  claim 1 , which comprises one or both of:
 (i) a VH comprising an amino acid sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues from, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology with, the amino acid sequence of the VH of a monoclonal antibody chosen from antibodies 3525, 3530, 3833, 3631, 3732, 4540, 4540-063, or 4540-033; or   (ii) a VL comprising an amino acid sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues from, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology with, the amino acid sequence of the VL of the monoclonal antibody.   
     
     
         10 . An anti-APRIL antibody molecule, which binds, or substantially binds, to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more, residues within a region of human APRIL as defined in any of Tables 3-4 or 7-8. 
     
     
         11 . The antibody molecule of  claim 10 , which has one, two, or all of:
 (a) binds, or substantially binds, to an epitope that comprises one or more APRIL residues from monomer A and one or more APRIL residues from monomer B as shown in Table 3 or 8;   (b) binds, or substantially binds, to one or more APRIL residues from the C-D loop, the G-H loop, or both; or   (c) does not bind, or binds with low affinity, to one, two or all of Asp129, Arg233, or His203 of human APRIL.   
     
     
         12 . The antibody molecule of  claim 10 , which:
 (a) binds, or substantially binds, to 1, 2, 3, 4, 5, or all of the amino acid residues of human APRIL chosen from V174, F176, Q190, R195, R206, or Y208, wherein the antibody molecule does not binds, or binds with low affinity, to 1, 2, 3, or all of the amino acid residues of human APRIL chosen from V181, S226, I228, or N237; or   (b) binds, or substantially binds, to 1, 2, 3, or all of the amino acid residues of human APRIL chosen from F176, V181, Q190, or I228, wherein the antibody molecule does not bind, or does not substantially bind, to one or both of the amino acid residues of human APRIL chosen from Y208 or N237.   
     
     
         13 . The antibody molecule of any of  claim 10 , which binds, or substantially binds, to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or all of the amino acid residues of human APRIL chosen from V133, V181, E185, Q187, G188, R189, Q190, E191, T192, R195, H218, L219, H220, S226, I228, or P230 in monomer A, and V121, I123, Q139, P140, A141, L142, N237, 5239, P240, or H241 in monomer B. 
     
     
         14 . The antibody molecule of  claim 10 , which binds, or substantially binds, to a conformational epitope. 
     
     
         15 . The antibody molecule of  claim 10 , which comprises one or both of:
 (i) a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the following:   an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the HCDR1 of a monoclonal antibody chosen from 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 2419-1305, 2419-1306, 2419-1310, 2419-1406, 2922, 3327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237;   an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the HCDR2 of the monoclonal antibody; or   an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the HCDR3 of the monoclonal antibody; or   (ii) a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, two, or all of the following:   an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the LCDR1 of the monoclonal antibody;   an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the LCDR2 of the monoclonal antibody; or   an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the LCDR3 of the monoclonal antibody.   
     
     
         16 . The antibody molecule of  claim 10 , which comprises one or both of:
 (i) a VH comprising an amino acid sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues from, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology with, the amino acid sequence of the VH of a monoclonal antibody chosen from 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 2419-1305, 2419-1306, 2419-1310, 2419-1406, 2922, 3327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237;   (ii) a VL comprising an amino acid sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues from, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology with, the amino acid sequence of the VL of the monoclonal antibody.   
     
     
         17 . An anti-APRIL antibody molecule, which:
 (i) binds, or substantially binds, to human APRIL;   (ii) inhibits, or substantially inhibits, binding of APRIL to TACI;   (iii) inhibits, or substantially inhibits, binding of APRIL to BCMA; and   (iv) binds, or substantially binds, to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more, residues within a region of human APRIL as defined in any of Tables 3-4 or 7-8.   
     
     
         18 . The antibody molecule of  claim 17 , which binds, or substantially binds, to human APRIL at an EC 50  of 20 nM or less, 10 nM or less, 9 nM or less, 8 nM or less, 7 nM or less, 6 nM or less, 5 nM or less, 4 nM or less, 3 nM or less, 2 nM or less, 1 nM or less, 0.8 nM or less, 0.6 nM or less, 0.4 nM or less, 0.2 nM or less, 0.1 nM or less, 0.05 nM or less, 0.02 nM or less, 0.01 nM or less, 0.005 nM or less, 0.002 nM or less, 0.001 nM or less, between 0.001 nM and 20 nM, between 0.01 nM and 20 nM, between 0.1 nM and 20 nM, between 0.1 nM and 10 nM, between 0.5 nM and 5 nM, between 1 nM and 5 nM, between 0.001 nM and 0.1 nM, between 0.001 nM and 0.01 nM, between 0.001 nM and 0.005 nM, between 0.01 nM and 0.05 nM, or between 0.01 nM and 0.1 nM. 
     
     
         19 . The antibody molecule of  claim 17 , which does not bind to mouse APRIL, or binds to mouse APRIL at an EC 50  of 1000 nM or more, 2000 nM or more. 
     
     
         20 . The antibody molecule of  claim 17 , which inhibits, or substantially inhibits, binding of APRIL to TACI at an IC 50  of 50 nM or less, 40 nM or less, 30 nM or less, 20 nM or less, 10 nM or less, 9 nM or less, 8 nM or less, 7 nM or less, 6 nM or less, 5 nM or less, 4 nM or less, 3 nM or less, 2 nM or less, 1 nM or less, 0.8 nM or less, 0.6 nM or less, 0.4 nM or less, 0.2 nM or less, 0.1 nM or less, 0.05 nM or less, 0.002 nM or less, 0.001 nM or less, between 0.001 nM and 50 nM, between 0.01 nM and 50 nM, between 0.1 nM and 50 nM, between 0.1 nM and 25 nM, between 0.1 nM and 10 nM, between 0.5 nM and 5 nM, between 1 nM and 5 nM, between 0.001 nM and 0.1 nM, between 0.001 nM and 0.01 nM, between 0.001 nM and 0.005 nM, between 0.01 nM and 0.05 nM, or between 0.01 nM and 0.1 nM. 
     
     
         21 . The antibody molecule of  claim 17 , which inhibits, or substantially inhibits, binding of APRIL to BCMA at an IC 50  of 200 nM or less, 150 nM or less, 100 nM or less, 50 nM or less, 40 nM or less, 30 nM or less, 20 nM or less, 10 nM or less, 9 nM or less, 8 nM or less, 7 nM or less, 6 nM or less, 5 nM or less, 4 nM or less, 3 nM or less, 2 nM or less, 1 nM or less, 0.8 nM or less, 0.6 nM or less, 0.4 nM or less, 0.2 nM or less, 0.1 nM or less, 0.05 nM or less, 0.02 nM or less, 0.01 nM or less, 0.005 nM or less, 0.002 nM or less, 0.001 nM or less, between 0.001 nM and 100 nM, between 0.001 nM and 50 nM, between 0.01 nM and 20 nM, between 0.1 nM and 10 nM, between 0.5 nM and 5 nM or between 1 nM and 5 nM, between 0.001 nM and 0.1 nM, between 0.001 nM and 0.01 nM, between 0.001 nM and 0.005 nM, between 0.01 nM and 0.05 nM, or between 0.01 nM and 0.1 nM. 
     
     
         22 . The antibody molecule of  claim 17 , which has one, two, or all of:
 (a) binds, or substantially binds, to an epitope that comprises one or more APRIL residues from monomer A and one or more APRIL residues from monomer B as shown in Table 3 or 8; or   (b) binds, or substantially binds, to one or more APRIL residues from the C-D loop, the G-H loop, or both; or   (c) does not bind, or binds with low affinity, to one, two or all of Asp129, Arg233, or His203 of human APRIL.   
     
     
         23 . The antibody molecule of  claim 17 , which comprises one or both of:
 (i) a heavy chain variable region (VH) comprising one, two, or all of the following:   an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the HCDR1 of a monoclonal antibody chosen from antibodies 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 2419-1305, 2419-1306, 2419-1310, 2419-1406, 2922, 3327, 3125, 2621, 4035, 4035-062, 3934, 4338, 4439, or 4237;   an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the HCDR2 of the monoclonal antibody; or   an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the HCDR3 of the monoclonal antibody, or   (ii) a light chain variable region (VL) comprising one, two, or all of the following:   an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the LCDR1 of the monoclonal antibody;   an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the LCDR2 of the monoclonal antibody; or   an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the LCDR3 of the monoclonal antibody.   
     
     
         24 . The antibody molecule of  claim 17 , which comprises one or both of:
 (i) a VH comprising an amino acid sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues from, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology with, the amino acid sequence of the VH of a monoclonal antibody chosen from antibodies 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 2419-1305, 2419-1306, 2419-1310, 2419-1406, 2922, 3327, 3125, 2621, 4035, 4035-062, 3934, 4338, 4439, or 4237; or   (ii) a VL comprising an amino acid sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues from, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology with, the amino acid sequence of the VL of the monoclonal antibody.   
     
     
         25 . An anti-APRIL antibody molecule, comprising one or both of:
 (i) a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the following:   an HCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the HCDR1 of a monoclonal antibody chosen from 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 2419-1305, 2419-1306, 2419-1310, 2419-1406, 2922, 3327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237;   an HCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the HCDR2 of the monoclonal antibody; or   an HCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the HCDR3 of the monoclonal antibody, or   (ii) a light chain variable region (VH), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, two, or all of the following:   an LCDR1 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the LCDR1 of the monoclonal antibody;   an LCDR2 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the LCDR2 of the monoclonal antibody; or   an LCDR3 comprising an amino acid sequence that differs by no more than 1, 2, or 3 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of the LCDR3 of the monoclonal antibody.   
     
     
         26 . The antibody molecule of  claim 25 , which comprises one or both of:
 (i) a VH comprising an amino acid sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues from, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology with, the amino acid sequence of the VH of the monoclonal antibody; or   (ii) a VL comprising an amino acid sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues from, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology with, the amino acid sequence of the VL of the monoclonal antibody.   
     
     
         27 . The antibody molecule of  claim 25 , which is a synthetic antibody molecule, an isolated antibody molecule, or a humanized antibody molecule. 
     
     
         28 . The antibody molecule of  claim 25 , which comprises: (a) a heavy chain constant region of IgG1, IgG2, IgG3, or IgG4; (b) a light chain constant region of kappa or lambda light chain; or (c) both (a) and (b). 
     
     
         29 . The antibody molecule of  claim 25 , which comprises an Fc region, wherein the Fc region comprises:
 (a) one or more mutations located at the interface between the CH2 and CH3 domains;   (b) 1, 2, 3, 4, 6, or all of the mutations chosen from T250Q, M252Y, S254T, T256E, M428L, H433K, or N434F, of IgG1;   (c) one or more mutations at positions 233-236 or 322 of human IgG1 or IgG2, or one or more substitutions at positions 327, 330 or 331 of human IgG4; or   (d) 1, 2, 3, 4, 6 7, or all of the mutations chosen from E233P, L234V, L235A, G236, K322A, A327G, A330S, or P331S.   
     
     
         30 . The antibody molecule of  claim 25 , which comprises two heavy chain variable regions and two light chain variable regions, or is a Fab, F(ab′)2, Fv, Fd, or a single chain Fv fragment (scFv). 
     
     
         31 . An anti-APRIL antibody molecule, comprising:
 (a) one or both of:
 (i) a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the following: 
 an HCDR1 comprising an amino acid sequence of G-Y-T-F-T-D-Y (SEQ ID NO: 11); 
 an HCDR2 comprising an amino acid sequence of Y-P-L-R-G-S(SEQ ID NO: 12); or 
 an HCCDR3 comprising an amino acid sequence of H-G-A-Y-Y-S-N-A-F-D-Y (SEQ ID NO: 13), or 
 (ii) a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, two, or all of the following: 
 an LCDR1 comprising an amino acid sequence of X1-X2-S-X4-S-V-D-N-D-G-I-R-F-X14-H (SEQ ID NO: 327), wherein X1 is R or K; X2 is A or S; X4 is E or Q; and X14 is M or L; 
 an LCDR2 comprising an amino acid sequence of R-A-S-X4-X5-X6-X7 (SEQ ID NO: 328), wherein X4 is N or T; X5 is L or R; X6 is E or A; and X7 is S or T; or 
 an LCDR3 comprising an amino acid sequence of Q-Q-S-N-K-D-P-Y-T (SEQ ID NO: 16), or 
   (b) one or both of:
 (i) a heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable region comprises one, two, or all of the following: 
 an HCDR1 comprising an amino acid sequence of D-Y-T-I-H (SEQ ID NO: 17); 
 an HCDR2 comprising an amino acid sequence of W-I-Y-P-L-R-G-S-I-N-Y-X12-X13-X14-F-X16-X17 (SEQ ID NO: 329), wherein X12 is N, S, or A, X13 is E, P, or Q; X14 is K or S; X16 is K or Q; and X17 is D or G; or 
 an HCCDR3 comprising an amino acid sequence of H-G-A-Y-Y-S-N-A-F-D-Y (SEQ ID NO: 13), or 
 (ii) a light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises one, two, or all of the following: 
 an LCDR1 comprising an amino acid sequence of X1-X2-S-X4-S-V-D-N-D-G-I-R-F-X14-H (SEQ ID NO: 327), wherein X1 is R or K; X2 is A or S; X4 is E or Q; and X14 is M or L; 
 an LCDR2 comprising an amino acid sequence of R-A-S-X4-X5-X6-X7 (SEQ ID NO: 328), wherein X4 is N or T; X5 is L or R; X6 is E or A; and X7 is S or T; or 
 an LCDR3 comprising an amino acid sequence of Q-Q-S-N-K-D-P-Y-T (SEQ ID NO: 16). 
   
     
     
         32 . An anti-APRIL antibody molecule, which competes for binding to APRIL with the antibody molecule of  claim 25 . 
     
     
         33 . An anti-APRIL antibody molecule, which binds, or substantially binds, to an epitope that completely or partially overlaps with the epitope of the antibody molecule of  claim 25 . 
     
     
         34 . A pharmaceutical composition comprising the antibody molecule of  claim 25  and a pharmaceutically acceptable carrier. 
     
     
         35 . A nucleic acid molecule encoding a heavy chain variable region (VH), a light chain variable region (VL), or both, of the antibody molecule of  claim 25 . 
     
     
         36 . A vector comprising the nucleic acid molecule of  claim 35 . 
     
     
         37 . A cell comprising the nucleic acid molecule of  claim 35 . 
     
     
         38 . A kit comprising the antibody molecule of  claim 25  and instructions to use of the antibody molecule. 
     
     
         39 . A container comprising the antibody molecule of  claim 25 . 
     
     
         40 . A method of producing an anti-APRIL antibody molecule, the method comprising culturing a cell of  claim 37  under conditions that allow production of an antibody molecule, thereby producing the antibody molecule. 
     
     
         41 . A method of treating IgA nephropathy, the method comprising administering to a subject in need thereof an effective amount of the antibody molecule of  claim 25 , thereby treating IgA nephropathy. 
     
     
         42 . The method of  claim 41 , wherein the antibody molecule is administered to the subject intravenously. 
     
     
         43 . The method of  claim 41 , wherein the antibody molecule is administered to the subject at a dose between 0.1 mg/kg and 50 mg/kg, between 0.2 mg/kg and 25 mg/kg, between 0.5 mg/kg and 10 mg/kg, between 0.5 mg/kg and 5 mg/kg, between 0.5 mg/kg and 3 mg/kg, between 0.5 mg/kg and 2.5 mg/kg, between 0.5 mg/kg and 2 mg/kg, between 0.5 mg/kg and 1.5 mg/kg, between 0.5 mg/kg and 1 mg/kg, between 1 mg/kg and 1.5 mg/kg, between 1 mg/kg and 2 mg/kg, between 1 mg/kg and 2.5 mg/kg, between 1 mg/kg and 3 mg/kg, between 1 mg/kg and 2.5 mg/kg, or between 1 mg/kg and 5 mg/kg, or at a fixed dose between 10 mg and 1000 mg, between 10 mg and 500 mg, between 10 mg and 250 mg, between 10 mg and 150 mg, between 10 mg and 100 mg, between 10 mg and 50 mg, between 250 mg and 500 mg, between 150 mg and 500 mg, between 100 mg and 500 mg, between 50 mg and 500 mg, between 25 mg and 250 mg, between 50 mg and 150 mg, between 50 mg and 100 mg, between 100 mg and 150 mg. between 100 mg and 200 mg, or between 150 mg and 250 mg. 
     
     
         44 . The method of  claim 41 , wherein the antibody molecule is administered once a week, twice a week, once every two weeks, or once every four weeks. 
     
     
         45 . The method of  claim 41 , wherein administration of the antibody molecule reduces (a) the level of IgA in a peripheral tissue chosen from serum, mucosal tissue, or bone marrow; (b) the level of a variant of IgA chosen from IgA1, IgA1 in polymeric form (pIgA1), or IgA1 with an O-linked glycosylation variant; or (c) both (a) and (b). 
     
     
         46 . The method of  claim 41 , further comprising determining the level of IgA in a peripheral tissue sample, wherein the peripheral tissue is serum, mucosal tissue, or bone marrow. 
     
     
         47 . The method of  claim 41 , further comprising administering to the subject a second therapy for IgA nephropathy. 
     
     
         48 . The method of  claim 42 , wherein the second therapy is chosen from an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin receptor blocker (ARB), omega-3 fatty acids, an immunosuppressant, a statin, mycophenolate mofetil, or any combination thereof. 
     
     
         49 . A method of treating diabetic nephropathy, the method comprising administering to a subject in need thereof an effective amount of an antibody molecule of  claim 25 , thereby treating diabetic nephropathy. 
     
     
         50 . A method of treating cancer, the method comprising administering to a subject in need thereof an effective amount of the antibody molecule of  claim 25 , thereby treating cancer. 
     
     
         51 . The method of  claim 50 , wherein the cancer is a hematological cancer. 
     
     
         52 . The method of  claim 51 , wherein the hematological cancer is chosen from B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia (CLL), Hodgkin's lymphoma, multiple myeloma, Waldenström's macroglobulinemia, or lymphoplasmacytic lymphoma. 
     
     
         53 . A method of treating an immunoproliferative disorder, the method comprising administering to a subject in need thereof an effective amount of the antibody molecule of  claim 25 , thereby treating the immunoproliferative disorder. 
     
     
         54 . The method of  claim 53 , wherein the immunoproliferative disorder is monoclonal IgA hypergammaglobulinemia. 
     
     
         55 . A method of treating vasculitis, the method comprising administering to a subject in need thereof an effective amount of the antibody molecule of  claim 25 , thereby treating vasculitis. 
     
     
         56 . The method of  claim 55 , wherein the vasculitis is kidney vasculitis or an IgA associated vasculitis or post-streptococcal glomerulonephritis. 
     
     
         57 . A method of treating an autoimmune disorder, the method comprising administering to a subject in need thereof an effective amount of the antibody molecule of  claim 25 , thereby treating an autoimmune disorder. 
     
     
         58 . The method of  claim 57 , wherein the autoimmune disorder is chosen from rheumatoid arthritis, systemic lupus erythematosus, a linear IgA bullous disease, or IgA-mediated epidermolysis bullosa acquisita. 
     
     
         59 . A method of treating IgA pemphigus, the method comprising administering to a subject in need thereof an effective amount of the antibody molecule of  claim 25 , thereby treating IgA pemphigus. 
     
     
         60 . A method of treating celiac disease, the method comprising administering to a subject in need thereof an effective amount of the antibody molecule of  claim 25 , thereby treating celiac disease. 
     
     
         61 . A method of treating alcoholic cirrhosis, the method comprising administering to a subject in need thereof an effective amount of the antibody molecule of  claim 25 , thereby treating alcoholic cirrhosis. 
     
     
         62 . A method of reducing the level of IgA in a cell or subject, the method comprising contacting the cell or subject the antibody molecule of  claim 25 , thereby reducing the level of IgA. 
     
     
         63 . A method of detecting an APRIL molecule, the method comprising contacting a cell or a sample from a subject with the antibody molecule of  claim 25 , thereby detecting the APRIL molecule.