Antibody molecules against APRIL and uses thereof

Abstract

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

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 374,646, filed September 6, 2022, and U.S. Provisional Application No. 63 / 334,381, filed April 25, 2022. The contents of the above applications are hereby incorporated by reference in their entirety.

[0003] Sequence Listing

[0004] This application contains a sequence listing submitted electronically in XML format and is hereby incorporated by reference in its entirety. The XML copy created on April 20, 2023 is named P2029-7047TW_SL.xml and is 348,201 bytes in size. Background Art

[0005] IgA nephropathy is one of the most prevalent chronic glomerular diseases worldwide. Conservative epidemiological estimates indicate a global incidence of approximately 5-50 cases per million children and 10-40 cases per million adults. The disease prevalence exhibits a regional prevalence, with higher rates in Asia and the Americas, and a particularly high burden in Japan and China. In Japan, the estimated number of biopsy-proven cases of IgA nephropathy is approximately 350,000. In the United States, the estimated number is approximately 100,000, making it the most commonly diagnosed type I glomerular disease in adults. Although IgA nephropathy is a relatively indolent disease, it leads to end-stage renal disease (ESRD), defined as renal failure in 20-30 years in 20-50% of patients. These figures are likely to be significant underestimates, given the need for renal biopsy confirmation, which varies across clinical settings. The disease has a complex pathogenesis, with genetic, epidemiological, and potentially environmental factors influencing disease etiology, pathology, and progression. It also presents with diverse clinical manifestations, ranging from asymptomatic to end-stage renal failure (ESRD). IgA nephropathy is caused by IgA deposition, typically in the form of mesangial immune complexes. There are currently no disease-specific treatments for the primary disease or its progression.

[0006] There is a need to develop new approaches for the treatment, prevention, and diagnosis of IgA nephropathy and other conditions with similar disease mechanisms. Summary of the Invention

[0007] Therefore, in certain aspects, the present disclosure provides a method of improving renal function, the method comprising administering an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule as described herein) to a subject in need thereof, thereby improving renal function. In some embodiments, the method reverses or prevents the progression of decreased renal function in the subject. In some embodiments, the improved renal function comprises renal regeneration. In some embodiments, the improved renal function comprises an increase in the estimated glomerular filtration rate (eGFR) of the subject's kidney. In some embodiments, the improved renal function comprises a decrease in proteinuria in the subject's kidney.

[0008] In one aspect, the present disclosure provides a method of preserving (e.g., maintaining or increasing) eGFR in the kidney of a subject in need thereof, the method comprising administering an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule as described herein) to the subject, thereby preserving (e.g., maintaining or increasing) eGFR in the kidney of the subject.

[0009] In some embodiments, the average eGFR over a period of at least twelve months after administration of the antibody molecule is greater than or equal to the subject's baseline eGFR. In some embodiments, the administration maintains the subject's renal eGFR, e.g., the average eGFR over a period of at least twelve months after administration of the antibody molecule is equal to or substantially equal to the subject's baseline eGFR. In some embodiments, the administration increases the subject's renal eGFR, e.g., the average eGFR over a period of at least twelve months after administration of the antibody molecule is greater than the subject's baseline eGFR. In some embodiments, the subject's baseline eGFR is the eGFR prior to administration of the antibody molecule.

[0010] In one aspect, the present disclosure provides a method of reducing proteinuria in the kidneys of a subject in need thereof, the method comprising administering to the subject an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule as described herein), thereby reducing proteinuria in the kidneys of the subject. In some embodiments, the reduction in proteinuria is determined by measuring the urine protein / creatinine ratio (uPCR), e.g., as described herein.

[0011] In one aspect, the disclosure provides a method of inducing renal recovery in a subject in need thereof, comprising administering to the subject an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule as described herein), thereby inducing renal recovery in the subject's kidney.

[0012] In one aspect, the disclosure provides a method of inducing renal regeneration in a subject in need thereof, comprising administering to the subject an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule as described herein), thereby inducing renal regeneration in the subject's kidney.

[0013] In one aspect, the disclosure provides a method of reducing an autoantibody response in a subject in need thereof, comprising administering an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule as described herein) to the subject, thereby reducing the autoantibody response in the subject.

[0014] In some embodiments of any of the aspects disclosed herein, the anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and / or a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0015] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and / or the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0016] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and / or the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0017] In one aspect, the present disclosure also provides a method of treating a condition, comprising administering an anti-APRIL antibody molecule described herein to a subject in need thereof, wherein the antibody molecule is administered at a dose that reduces the level of abnormally glycosylated IgA (ag IgA) (e.g., abnormally glycosylated IgA1 (a-g IgA1)) in the subject by at least 40%, thereby treating the condition. In one embodiment, the level of ag IgA includes the level of ag IgA1 or the level of ag IgA1.

[0018] In one embodiment, the level of ag IgA is reduced by at least 40% about 4 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 8 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 12 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 16 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% for a predetermined period of time, for example, at least one, two, three or four weeks, or at least one, two or three months. In one embodiment, the level of ag IgA is reduced by at least 50%. In one embodiment, the level of a-g IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%. In one embodiment, the antibody molecule is administered in a single dose. In one embodiment, the antibody molecule is administered in repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0019] In one embodiment, the disorder is an APRIL-associated disorder. In one embodiment, the disorder is associated with abnormal levels of total IgA. In one embodiment, the disorder is a disorder associated with ag IgA (e.g., ag IgAl).

[0020] In one embodiment, the disorder is IgA nephropathy (IgAN). In one embodiment, the IgAN is familial IgAN. In one embodiment, the IgAN is adult IgAN. In one embodiment, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0021] In one embodiment, the condition is chronic kidney disease (CKD) or a condition associated with CKD. In one embodiment, the CKD is advanced CKD, e.g., with an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0022] In one embodiment, the condition is Henoch-Schonlein purpura (HSP). In one embodiment, the condition is cutaneous vasculitis or IgA vasculitis. In one embodiment, the condition is IgA dermatitis, e.g., IgA bullous dermatosis. In one embodiment, the condition is Waldenstrom's macroglobulinemia (WM). In one embodiment, the condition is lupus nephritis.

[0023] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the ag IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the total IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not yet received or is not receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has or is identified as having the genome susceptibility locus of the disease (e.g., IgA nephropathy). In one embodiment, the method further comprises determining whether the subject has the genome susceptibility locus of the disease (e.g., IgA nephropathy).

[0024] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0025] In one embodiment, the level of ag IgA in a sample from a subject is determined. In one embodiment, the method described herein further comprises determining the level of ag IgA in a sample from a subject. In one embodiment, the method further comprises determining the level of total IgA in the sample. In one embodiment, the method further comprises determining the level of IgM and / or IgG in the sample. In one embodiment, the method further comprises obtaining a sample from a subject. In one embodiment, the sample is a blood or serum sample.

[0026] In one embodiment, the method further comprises administering to the subject a second therapeutic agent or treatment modality. In one embodiment, the second therapeutic agent or treatment modality is a small molecule. In one embodiment, the second therapeutic agent or treatment modality is an antibody molecule.

[0027] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject receives the vaccine before, simultaneously with, or after administration of the anti-APRIL antibody molecule.

[0028] In one embodiment, administration of the anti-APRIL antibody molecule reduces the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%. In one embodiment, administration of the anti-APRIL antibody molecule does not reduce or does not significantly reduce the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine. In one embodiment, a subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to a vaccine following administration of the anti-APRIL antibody molecule.

[0029] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or longer after administration of the anti-APRIL antibody molecule.

[0030] In one aspect, the present disclosure provides a method of treating a condition comprising administering an anti-APRIL antibody molecule to a subject in need thereof, wherein the administration reduces the level of ag IgA (e.g., ag IgA1) in the subject by at least 40%, thereby treating the condition. In one embodiment, the level of a-g IgA comprises the level of a-g IgA1 or is the level of a-g IgA1.

[0031] In one embodiment, the level of ag IgA is reduced by at least 40% about 4 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 8 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 12 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 16 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% for a predetermined period of time, for example, at least one, two, three or four weeks, or at least one, two or three months. In one embodiment, the level of ag IgA is reduced by at least 50%. In one embodiment, the level of a-g IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%. In one embodiment, the antibody molecule is administered in a single dose. In one embodiment, the antibody molecule is administered in repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0032] In one embodiment, the disorder is an APRIL-associated disorder. In one embodiment, the disorder is associated with abnormal levels of total IgA. In one embodiment, the disorder is a disorder associated with ag IgA (e.g., ag IgAl).

[0033] In one embodiment, the disorder is IgA nephropathy (IgAN). In one embodiment, the IgAN is familial IgAN. In one embodiment, the IgAN is adult IgAN. In one embodiment, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0034] In one embodiment, the condition is chronic kidney disease (CKD) or a condition associated with CKD. In one embodiment, the CKD is advanced CKD, e.g., with an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0035] In one embodiment, the condition is Henoch-Schonlein purpura (HSP). In one embodiment, the condition is cutaneous vasculitis or IgA vasculitis. In one embodiment, the condition is IgA dermatitis, e.g., IgA bullous dermatosis. In one embodiment, the condition is Waldenstrom's macroglobulinemia (WM). In one embodiment, the condition is lupus nephritis.

[0036] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the ag IgA level higher than the ag IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the total IgA level higher than the total IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not yet received or is not receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has or is identified as having the genome susceptibility locus of the disease (e.g., IgA nephropathy). In one embodiment, the method described herein also includes determining whether the subject has the genome susceptibility locus of the disease (e.g., IgA nephropathy).

[0037] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0038] In one embodiment, the level of ag IgA in a sample from a subject is determined. In one embodiment, the method further comprises measuring the level of ag IgA in a sample from a subject. In one embodiment, the method further comprises measuring the level of total IgA in the sample. In one embodiment, the method further comprises measuring the level of IgM and / or IgG in the sample. In one embodiment, the method further comprises obtaining a sample from a subject. In one embodiment, the sample is a blood or serum sample.

[0039] In one embodiment, the method further comprises administering to the subject a second therapeutic agent or treatment modality. In one embodiment, the second therapeutic agent or treatment modality is a small molecule. In one embodiment, the second therapeutic agent or treatment modality is an antibody molecule.

[0040] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject receives the vaccine before, simultaneously with, or after administration of the anti-APRIL antibody molecule.

[0041] In one embodiment, administration of the anti-APRIL antibody molecule reduces the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%. In one embodiment, administration of the anti-APRIL antibody molecule does not reduce or does not significantly reduce the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine. In one embodiment, a subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to a vaccine following administration of the anti-APRIL antibody molecule.

[0042] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or longer after administration of the anti-APRIL antibody molecule.

[0043] In yet another aspect, the present disclosure provides a method of treating a condition, comprising administering an anti-APRIL antibody molecule to a subject in need thereof, wherein the antibody molecule is administered at a dosage (e.g., dose and frequency) that reduces or is likely to reduce the subject's ag IgA (e.g., ag IgA1) level by at least 40%, thereby treating the condition. In one embodiment, the level of ag IgA includes the level of ag IgA1 or the level of ag IgA1.

[0044] In one embodiment, the level of ag IgA is reduced by at least 40% about 4 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 8 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 12 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 16 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% for a predetermined period of time, for example, at least one, two, three or four weeks, or at least one, two or three months. In one embodiment, the level of ag IgA is reduced by at least 50%. In one embodiment, the level of a-g IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%. In one embodiment, the antibody molecule is administered in a single dose. In one embodiment, the antibody molecule is administered in repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0045] In one embodiment, the disorder is an APRIL-associated disorder. In one embodiment, the disorder is associated with abnormal levels of total IgA. In one embodiment, the disorder is a disorder associated with ag IgA (e.g., ag IgAl).

[0046] In one embodiment, the disorder is IgA nephropathy (IgAN). In one embodiment, the IgAN is familial IgAN. In one embodiment, the IgAN is adult IgAN. In one embodiment, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0047] In one embodiment, the condition is chronic kidney disease (CKD) or a condition associated with CKD. In one embodiment, the CKD is advanced CKD, e.g., with an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0048] In one embodiment, the condition is Henoch-Schonlein purpura (HSP). In one embodiment, the condition is cutaneous vasculitis or IgA vasculitis. In one embodiment, the condition is IgA dermatitis, e.g., IgA bullous dermatosis. In one embodiment, the condition is Waldenstrom's macroglobulinemia (WM). In one embodiment, the condition is lupus nephritis.

[0049] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the ag IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the total IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not yet received or is not receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has or is identified as having the genome susceptibility locus of the disease (e.g., IgA nephropathy). In one embodiment, the method further comprises determining whether the subject has the genome susceptibility locus of the disease (e.g., IgA nephropathy).

[0050] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0051] In one embodiment, the level of ag IgA in a sample from a subject is determined. In one embodiment, the method further comprises measuring the level of ag IgA in a sample from a subject. In one embodiment, the method further comprises measuring the level of total IgA in the sample. In one embodiment, the method further comprises measuring the level of IgM and / or IgG in the sample. In one embodiment, the method further comprises obtaining a sample from a subject. In one embodiment, the sample is a blood or serum sample.

[0052] In one embodiment, the method further comprises administering to the subject a second therapeutic agent or treatment modality. In one embodiment, the second therapeutic agent or treatment modality is a small molecule. In one embodiment, the second therapeutic agent or treatment modality is an antibody molecule.

[0053] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject receives the vaccine before, simultaneously with, or after administration of the anti-APRIL antibody molecule.

[0054] In one embodiment, administration of the anti-APRIL antibody molecule reduces the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%. In one embodiment, administration of the anti-APRIL antibody molecule does not reduce or does not significantly reduce the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine. In one embodiment, a subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to a vaccine following administration of the anti-APRIL antibody molecule.

[0055] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or longer after administration of the anti-APRIL antibody molecule.

[0056] In another aspect, the present disclosure provides a method of treating a condition, comprising selecting a dose or dosage (e.g., dose and frequency) of an anti-APRIL antibody molecule, wherein administration of the antibody molecule at the dose or dosage reduces or may reduce the level of ag IgA (e.g., ag IgA1) in a subject in need thereof by at least 40%; and administering the antibody molecule to the subject at the selected dose or dosage, thereby treating the condition. In one embodiment, the level of ag IgA comprises the level of ag IgA1 or the level of ag IgA1.

[0057] In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 40% at about 4 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 40% at about 8 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 40% at about 12 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 40% at about 16 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 40% for a predetermined period of time, for example, at least one, two, three, or four weeks, or at least one, two, or three months. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 50%. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In one embodiment, the antibody molecule is administered as a single dose. In one embodiment, the antibody molecule is administered as repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0058] In one embodiment, the disorder is an APRIL-associated disorder. In one embodiment, the disorder is associated with abnormal levels of total IgA. In one embodiment, the disorder is a disorder associated with ag IgA (e.g., ag IgAl).

[0059] In one embodiment, the disorder is IgA nephropathy (IgAN). In one embodiment, the IgAN is familial IgAN. In one embodiment, the IgAN is adult IgAN. In one embodiment, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0060] In one embodiment, the condition is chronic kidney disease (CKD) or a condition associated with CKD. In one embodiment, the CKD is advanced CKD, e.g., with an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0061] In one embodiment, the condition is Henoch-Schonlein purpura (HSP). In one embodiment, the condition is cutaneous vasculitis or IgA vasculitis. In one embodiment, the condition is IgA dermatitis, e.g., IgA bullous dermatosis. In one embodiment, the condition is Waldenstrom's macroglobulinemia (WM). In one embodiment, the condition is lupus nephritis.

[0062] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the ag IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the total IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not yet received or is not receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has or is identified as having the genome susceptibility locus of the disease (e.g., IgA nephropathy). In one embodiment, the method further comprises determining whether the subject has the genome susceptibility locus of the disease (e.g., IgA nephropathy).

[0063] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0064] In one embodiment, the level of ag IgA in a sample from a subject is determined. In one embodiment, the method further comprises measuring the level of ag IgA in a sample from a subject. In one embodiment, the method further comprises measuring the level of total IgA in the sample. In one embodiment, the method further comprises measuring the level of IgM and / or IgG in the sample. In one embodiment, the method further comprises obtaining a sample from a subject. In one embodiment, the sample is a blood or serum sample.

[0065] In one embodiment, the method further comprises administering to the subject a second therapeutic agent or treatment modality. In one embodiment, the second therapeutic agent or treatment modality is a small molecule. In one embodiment, the second therapeutic agent or treatment modality is an antibody molecule.

[0066] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject receives the vaccine before, simultaneously with, or after administration of the anti-APRIL antibody molecule.

[0067] In one embodiment, administration of the anti-APRIL antibody molecule reduces the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%. In one embodiment, administration of the anti-APRIL antibody molecule does not reduce or does not significantly reduce the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine. In one embodiment, a subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to a vaccine following administration of the anti-APRIL antibody molecule.

[0068] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or longer after administration of the anti-APRIL antibody molecule.

[0069] In one aspect, the present disclosure provides a method of treating a condition, comprising administering an anti-APRIL antibody molecule to a subject in need thereof, in response to determining that administration of the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA (e.g., ag IgA1) by at least 40%, thereby treating the condition. In one embodiment, the level of ag IgA comprises the level of ag IgA1 or the level of ag IgA1.

[0070] In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% at about 4 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% at about 8 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% at about 12 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% at about 16 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% for a predetermined period of time, for example, at least one, two, three or four weeks, or at least one, two or three months. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 50%. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In one embodiment, the antibody molecule is administered as a single dose. In one embodiment, the antibody molecule is administered as repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0071] In one embodiment, the disorder is an APRIL-associated disorder. In one embodiment, the disorder is associated with abnormal levels of total IgA. In one embodiment, the disorder is a disorder associated with ag IgA (e.g., ag IgAl).

[0072] In one embodiment, the disorder is IgA nephropathy (IgAN). In one embodiment, the IgAN is familial IgAN. In one embodiment, the IgAN is adult IgAN. In one embodiment, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0073] In one embodiment, the condition is chronic kidney disease (CKD) or a condition associated with CKD. In one embodiment, the CKD is advanced CKD, e.g., with an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0074] In one embodiment, the condition is Henoch-Schonlein purpura (HSP). In one embodiment, the condition is cutaneous vasculitis or IgA vasculitis. In one embodiment, the condition is IgA dermatitis, e.g., IgA bullous dermatosis. In one embodiment, the condition is Waldenstrom's macroglobulinemia (WM). In one embodiment, the condition is lupus nephritis.

[0075] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the ag IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the total IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not yet received or is not receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has or is identified as having the genome susceptibility locus of the disease (e.g., IgA nephropathy). In one embodiment, the method further comprises determining whether the subject has the genome susceptibility locus of the disease (e.g., IgA nephropathy).

[0076] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0077] In one embodiment, the level of ag IgA in a sample from a subject is determined. In one embodiment, the method further comprises measuring the level of ag IgA in a sample from a subject. In one embodiment, the method further comprises measuring the level of total IgA in the sample. In one embodiment, the method further comprises measuring the level of IgM and / or IgG in the sample. In one embodiment, the method further comprises obtaining a sample from a subject. In one embodiment, the sample is a blood or serum sample.

[0078] In one embodiment, the method further comprises administering to the subject a second therapeutic agent or treatment modality. In one embodiment, the second therapeutic agent or treatment modality is a small molecule. In one embodiment, the second therapeutic agent or treatment modality is an antibody molecule.

[0079] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject receives the vaccine before, simultaneously with, or after administration of the anti-APRIL antibody molecule.

[0080] In one embodiment, administration of the anti-APRIL antibody molecule reduces the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%. In one embodiment, administration of the anti-APRIL antibody molecule does not reduce or does not significantly reduce the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine. In one embodiment, a subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to a vaccine following administration of the anti-APRIL antibody molecule.

[0081] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or longer after administration of the anti-APRIL antibody molecule.

[0082] In another aspect, the present disclosure provides a method of treating a condition, comprising determining whether administration of an anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA (e.g., ag IgA1) in a subject in need thereof by at least 40%, and initiating, continuing, or maintaining administration of the antibody molecule if the antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40%. In one embodiment, the level of ag IgA comprises the level of ag IgA1 or is the level of ag IgA1.

[0083] In one embodiment, if the antibody molecule does not or is unlikely to reduce the levels of ag IgA by at least 40%, administration of the antibody molecule is stopped, interrupted or modified. In one embodiment, if the antibody molecule does not or is unlikely to reduce the levels of ag IgA by at least 40%, a different therapeutic agent or treatment modality is administered.

[0084] In one embodiment, the level of ag IgA is reduced by at least 40% about 4 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 8 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 12 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 16 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% for a predetermined period of time, for example, at least one, two, three or four weeks, or at least one, two or three months. In one embodiment, the level of ag IgA is reduced by at least 50%. In one embodiment, the level of a-g IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%. In one embodiment, the antibody molecule is administered in a single dose. In one embodiment, the antibody molecule is administered in repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0085] In one embodiment, the disorder is an APRIL-associated disorder. In one embodiment, the disorder is associated with abnormal levels of total IgA. In one embodiment, the disorder is a disorder associated with ag IgA (e.g., ag IgAl).

[0086] In one embodiment, the disorder is IgA nephropathy (IgAN). In one embodiment, the IgAN is familial IgAN. In one embodiment, the IgAN is adult IgAN. In one embodiment, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0087] In one embodiment, the condition is chronic kidney disease (CKD) or a condition associated with CKD. In one embodiment, the CKD is advanced CKD, e.g., with an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0088] In one embodiment, the condition is Henoch-Schonlein purpura (HSP). In one embodiment, the condition is cutaneous vasculitis or IgA vasculitis. In one embodiment, the condition is IgA dermatitis, e.g., IgA bullous dermatosis. In one embodiment, the condition is Waldenstrom's macroglobulinemia (WM). In one embodiment, the condition is lupus nephritis.

[0089] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the ag IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the total IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not yet received or is not receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has or is identified as having the genome susceptibility locus of the disease (e.g., IgA nephropathy). In one embodiment, the method further comprises determining whether the subject has the genome susceptibility locus of the disease (e.g., IgA nephropathy).

[0090] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0091] In one embodiment, the level of ag IgA in a sample from a subject is determined. In one embodiment, the method further comprises measuring the level of ag IgA in a sample from a subject. In one embodiment, the method further comprises measuring the level of total IgA in the sample. In one embodiment, the method further comprises measuring the level of IgM and / or IgG in the sample. In one embodiment, the method further comprises obtaining a sample from a subject. In one embodiment, the sample is a blood or serum sample.

[0092] In one embodiment, the method further comprises administering to the subject a second therapeutic agent or treatment modality. In one embodiment, the second therapeutic agent or treatment modality is a small molecule. In one embodiment, the second therapeutic agent or treatment modality is an antibody molecule.

[0093] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject receives the vaccine before, simultaneously with, or after administration of the anti-APRIL antibody molecule.

[0094] In one embodiment, administration of the anti-APRIL antibody molecule reduces the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%. In one embodiment, administration of the anti-APRIL antibody molecule does not reduce or does not significantly reduce the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine. In one embodiment, a subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to a vaccine following administration of the anti-APRIL antibody molecule.

[0095] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or longer after administration of the anti-APRIL antibody molecule.

[0096] In yet another aspect, the present disclosure provides a method of treating a condition, the method comprising determining whether administration of an anti-APRIL antibody molecule at a dose or dosage reduces or is likely to reduce the level of ag IgA1 (e.g., ag IgA1) in a subject in need thereof by at least 40%, and initiating, continuing, or maintaining administration of the antibody molecule at said dose or dosage if the antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at said dose or dosage. In one embodiment, the level of ag IgA comprises the level of a-g IgA1 or the level of ag IgA1.

[0097] In one embodiment, if the antibody molecule at said dose or dosage does not or is unlikely to reduce the level of ag IgA by at least 40%, administration of said dose or dosage of the antibody molecule is stopped, interrupted or changed.

[0098] In one embodiment, the level of ag IgA is reduced by at least 40% about 4 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 8 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 12 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 16 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% for a predetermined period of time, for example, at least one, two, three or four weeks, or at least one, two or three months. In one embodiment, the level of ag IgA is reduced by at least 50%. In one embodiment, the level of a-g IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%. In one embodiment, the antibody molecule is administered in a single dose. In one embodiment, the antibody molecule is administered in repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0099] In one embodiment, the disorder is an APRIL-associated disorder. In one embodiment, the disorder is associated with abnormal levels of total IgA. In one embodiment, the disorder is a disorder associated with ag IgA (e.g., ag IgA1).

[0100] In one embodiment, the disorder is IgA nephropathy (IgAN). In one embodiment, the IgAN is familial IgAN. In one embodiment, the IgAN is adult IgAN. In one embodiment, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0101] In one embodiment, the condition is chronic kidney disease (CKD) or a condition associated with CKD. In one embodiment, the CKD is advanced CKD, e.g., with an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0102] In one embodiment, the condition is Henoch-Schonlein purpura (HSP). In one embodiment, the condition is cutaneous vasculitis or IgA vasculitis. In one embodiment, the condition is IgA dermatitis, e.g., IgA bullous dermatosis. In one embodiment, the condition is Waldenstrom's macroglobulinemia (WM). In one embodiment, the condition is lupus nephritis.

[0103] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the ag IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the total IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not yet received or is not receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has or is identified as having the genome susceptibility locus of the disease (e.g., IgA nephropathy). In one embodiment, the method further comprises determining whether the subject has the genome susceptibility locus of the disease (e.g., IgA nephropathy).

[0104] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0105] In one embodiment, the level of ag IgA in a sample from a subject is determined. In one embodiment, the method further comprises measuring the level of ag IgA in a sample from a subject. In one embodiment, the method further comprises measuring the level of total IgA in the sample. In one embodiment, the method further comprises measuring the level of IgM and / or IgG in the sample. In one embodiment, the method further comprises obtaining a sample from a subject. In one embodiment, the sample is a blood or serum sample.

[0106] In one embodiment, the method further comprises administering to the subject a second therapeutic agent or treatment modality. In one embodiment, the second therapeutic agent or treatment modality is a small molecule. In one embodiment, the second therapeutic agent or treatment modality is an antibody molecule.

[0107] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject receives the vaccine before, simultaneously with, or after administration of the anti-APRIL antibody molecule.

[0108] In one embodiment, administration of the anti-APRIL antibody molecule reduces the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%. In one embodiment, administration of the anti-APRIL antibody molecule does not reduce or does not significantly reduce the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine. In one embodiment, a subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to a vaccine following administration of the anti-APRIL antibody molecule.

[0109] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or longer after administration of the anti-APRIL antibody molecule.

[0110] In one aspect, the present disclosure provides a method of treating a condition, comprising determining whether a therapeutic agent or treatment modality other than an anti-APRIL antibody molecule described herein reduces or is likely to reduce the level of ag IgA by at least 40% in a subject in need thereof, and administering an anti-APRIL antibody molecule described herein to the subject if the therapeutic agent or treatment modality does not reduce or is unlikely to reduce the level of ag IgA by at least 40%. In one embodiment, the antibody molecule is administered at a dose or dosage that reduces or is likely to reduce the level of ag IgA in the subject by at least 40%. In one embodiment, the level of ag IgA comprises the level of ag IgA1 or the level of ag IgA1.

[0111] In one embodiment, the therapeutic agent or treatment modality reduces or may reduce the level of ag IgA by at least 40% approximately 4 weeks after administration of the antibody molecule. In one embodiment, the therapeutic agent or treatment modality reduces or may reduce the level of ag IgA by at least 40% approximately 8 weeks after administration of the antibody molecule. In one embodiment, the therapeutic agent or treatment modality reduces or may reduce the level of ag IgA by at least 40% approximately 12 weeks after administration of the antibody molecule. In one embodiment, the therapeutic agent or treatment modality reduces or may reduce the level of ag IgA by at least 40% approximately 16 weeks after administration of the antibody molecule. In one embodiment, the therapeutic agent or treatment modality reduces or may reduce the level of ag IgA by at least 40% for a predetermined period of time, e.g., at least one, two, three, or four weeks, or at least one, two, or three months. In one embodiment, the therapeutic agent or treatment modality reduces or may reduce the level of ag IgA by at least 50%. In one embodiment, the therapeutic agent or treatment modality reduces or may reduce the level of ag IgA by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In one embodiment, the therapeutic agent or treatment modality is administered in a single dose. In one embodiment, the therapeutic agent or treatment modality is administered in repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0112] In one embodiment, the disorder is associated with abnormal levels of total IgA. In one embodiment, the disorder is a disorder associated with ag IgA (eg, ag IgAl).

[0113] In one embodiment, the disorder is IgA nephropathy (IgAN). In one embodiment, the IgAN is familial IgAN. In one embodiment, the IgAN is adult IgAN. In one embodiment, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0114] In one embodiment, the condition is chronic kidney disease (CKD) or a condition associated with CKD. In one embodiment, the CKD is advanced CKD, e.g., with an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0115] In one embodiment, the condition is Henoch-Schonlein purpura (HSP). In one embodiment, the condition is cutaneous vasculitis or IgA vasculitis. In one embodiment, the condition is IgA dermatitis, e.g., IgA bullous dermatosis. In one embodiment, the condition is Waldenstrom's macroglobulinemia (WM). In one embodiment, the condition is lupus nephritis.

[0116] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the ag IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the total IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not yet received or is not receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has or is identified as having the genome susceptibility locus of the disease (e.g., IgA nephropathy). In one embodiment, the method further comprises determining whether the subject has the genome susceptibility locus of the disease (e.g., IgA nephropathy).

[0117] In one embodiment, the anti-APRIL antibody molecules include 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0118] In one embodiment, the level of ag IgA in a sample from a subject is determined. In one embodiment, the method further comprises measuring the level of ag IgA in a sample from a subject. In one embodiment, the method further comprises measuring the level of total IgA in the sample. In one embodiment, the method further comprises measuring the level of IgM and / or IgG in the sample. In one embodiment, the method further comprises obtaining a sample from a subject. In one embodiment, the sample is a blood or serum sample.

[0119] In one embodiment, the method further comprises administering to the subject a second therapeutic agent or treatment modality. In one embodiment, the second therapeutic agent or treatment modality is a small molecule. In one embodiment, the second therapeutic agent or treatment modality is an antibody molecule.

[0120] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject receives the vaccine before, simultaneously with, or after administration of the anti-APRIL antibody molecule.

[0121] In one embodiment, administration of the anti-APRIL antibody molecule reduces the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%. In one embodiment, administration of the anti-APRIL antibody molecule does not reduce or does not significantly reduce the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine. In one embodiment, a subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to a vaccine following administration of the anti-APRIL antibody molecule.

[0122] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or longer after administration of the anti-APRIL antibody molecule.

[0123] In another aspect, the present disclosure provides a method for reducing the level of ag IgA (e.g., ag IgA1) in a subject, the method comprising administering an anti-APRIL antibody molecule to a subject in need thereof, e.g., at a dose or dosage that reduces or may reduce the level of ag IgA in the subject by at least 40%, thereby reducing the level of ag IgA. In one embodiment, the level of a-g IgA includes the level of a-g IgA1 or the level of a-g IgA1.

[0124] In one embodiment, the level of ag IgA is reduced by at least 40% about 4 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 8 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 12 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% about 16 weeks after administration of the antibody molecule. In one embodiment, the level of ag IgA is reduced by at least 40% for a predetermined period of time, for example, at least one, two, three or four weeks, or at least one, two or three months. In one embodiment, the level of ag IgA is reduced by at least 50%. In one embodiment, the level of a-g IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%. In one embodiment, the antibody molecule is administered in a single dose. In one embodiment, the antibody molecule is administered in repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0125] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the ag IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the total IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not yet received or is not receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has or is identified as having the genome susceptibility locus of the disease (e.g., IgA nephropathy). In one embodiment, the method further comprises determining whether the subject has the genome susceptibility locus of the disease (e.g., IgA nephropathy).

[0126] In one embodiment, the subject has or is identified as having an APRIL-related disorder. In one embodiment, the subject has or is identified as having a disorder associated with abnormal levels of total IgA. In one embodiment, the subject has or is identified as having a disorder associated with ag IgA (e.g., ag IgAl).

[0127] In one embodiment, the subject has or is identified as having IgA nephropathy (IgAN). In one embodiment, the IgAN is familial IgAN. In one embodiment, the IgAN is adult IgAN. In one embodiment, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0128] In one embodiment, the subject has or is identified as having chronic kidney disease (CKD) or a condition associated with CKD. In one embodiment, the CKD is advanced CKD, e.g., an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0129] In one embodiment, the subject is suffering from or is identified as having Henoch-Schonlein purpura (HSP). In one embodiment, the subject is suffering from or is identified as having cutaneous vasculitis or IgA vasculitis. In one embodiment, the subject is suffering from or is identified as having IgA dermatitis, e.g., IgA bullous dermatosis. In one embodiment, the subject is suffering from or is identified as having Waldenstrom's macroglobulinemia (WM). In one embodiment, the subject is suffering from or is identified as having lupus nephritis.

[0130] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0131] In one embodiment, the level of ag IgA in a sample from a subject is determined. In one embodiment, the method further comprises measuring the level of ag IgA in a sample from a subject. In one embodiment, the method further comprises measuring the level of total IgA in the sample. In one embodiment, the method further comprises measuring the level of IgM and / or IgG in the sample. In one embodiment, the method further comprises obtaining a sample from a subject. In one embodiment, the sample is a blood or serum sample.

[0132] In one embodiment, the method further comprises administering to the subject a second therapeutic agent or treatment modality. In one embodiment, the second therapeutic agent or treatment modality is a small molecule. In one embodiment, the second therapeutic agent or treatment modality is an antibody molecule.

[0133] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject receives the vaccine before, simultaneously with, or after administration of the anti-APRIL antibody molecule.

[0134] In one embodiment, administration of the anti-APRIL antibody molecule reduces the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%. In one embodiment, administration of the anti-APRIL antibody molecule does not reduce or does not significantly reduce the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine. In one embodiment, a subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to a vaccine following administration of the anti-APRIL antibody molecule.

[0135] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or longer after administration of the anti-APRIL antibody molecule.

[0136] In yet another aspect, the present disclosure provides a method for selecting an anti-APRIL antibody molecule for treating a condition, the method comprising determining whether administration of the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA (e.g., ag IgA1) in a subject in need thereof by at least 40%, thereby selecting the anti-APRIL antibody molecule. In one embodiment, the level of a-g IgA comprises the level of ag IgA1 or is the level of ag IgA1.

[0137] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0138] In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% at about 4 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% at about 8 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% at about 12 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% at about 16 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% for a predetermined period of time, for example, at least one, two, three or four weeks, or at least one, two or three months. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 50%. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In one embodiment, the antibody molecule is administered as a single dose. In one embodiment, the antibody molecule is administered as repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0139] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the ag IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the total IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not yet received or is not receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has or is identified as having the genome susceptibility locus of the disease (e.g., IgA nephropathy). In one embodiment, the method further comprises determining whether the subject has the genome susceptibility locus of the disease (e.g., IgA nephropathy).

[0140] In one embodiment, the subject has or is identified as having an APRIL-related disorder. In one embodiment, the subject has or is identified as having a disorder associated with abnormal levels of total IgA. In one embodiment, the subject has or is identified as having a disorder associated with ag IgA (e.g., ag IgAl).

[0141] In one embodiment, the subject has or is identified as having IgA nephropathy (IgAN). In one embodiment, the IgAN is familial IgAN. In one embodiment, the IgAN is adult IgAN. In one embodiment, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0142] In one embodiment, the subject has or is identified as having chronic kidney disease (CKD) or a condition associated with CKD. In one embodiment, the CKD is advanced CKD, e.g., an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0143] In one embodiment, the subject is suffering from or is identified as having Henoch-Schonlein purpura (HSP). In one embodiment, the subject is suffering from or is identified as having cutaneous vasculitis or IgA vasculitis. In one embodiment, the subject is suffering from or is identified as having IgA dermatitis, e.g., IgA bullous dermatosis. In one embodiment, the subject is suffering from or is identified as having Waldenstrom's macroglobulinemia (WM). In one embodiment, the subject is suffering from or is identified as having lupus nephritis.

[0144] In one embodiment, the level of ag IgA in a sample from a subject is determined. In one embodiment, the method further comprises measuring the level of ag IgA in a sample from a subject. In one embodiment, the method further comprises measuring the level of total IgA in the sample. In one embodiment, the method further comprises measuring the level of IgM and / or IgG in the sample. In one embodiment, the method further comprises obtaining a sample from a subject. In one embodiment, the sample is a blood or serum sample.

[0145] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject receives the vaccine before, simultaneously with, or after administration of the anti-APRIL antibody molecule.

[0146] In one embodiment, administration of the anti-APRIL antibody molecule reduces the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%. In one embodiment, administration of the anti-APRIL antibody molecule does not reduce or does not significantly reduce the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine. In one embodiment, a subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to a vaccine following administration of the anti-APRIL antibody molecule.

[0147] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or longer after administration of the anti-APRIL antibody molecule.

[0148] In another aspect, the present disclosure provides a method for selecting a dose or dosage (e.g., dose and frequency) of an anti-APRIL antibody molecule to treat a condition, the method comprising determining whether administration of the anti-APRIL antibody molecule at the dose or dosage reduces or is likely to reduce the level of a-g IgA (e.g., ag IgA1) in a subject in need thereof by at least 40%, thereby selecting the dose or dosage. In one embodiment, the level of ag IgA includes the level of ag IgA1 or the level of ag IgA1.

[0149] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0150] In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 40% at about 4 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 40% at about 8 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 40% at about 12 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 40% at about 16 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 40% for a predetermined period of time, for example, at least one, two, three, or four weeks, or at least one, two, or three months. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 50%. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In one embodiment, the antibody molecule is administered as a single dose. In one embodiment, the antibody molecule is administered as repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0151] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the ag IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the total IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not yet received or is not receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has or is identified as having the genome susceptibility locus of the disease (e.g., IgA nephropathy). In one embodiment, the method further comprises determining whether the subject has the genome susceptibility locus of the disease (e.g., IgA nephropathy).

[0152] In one embodiment, the subject has or is identified as having an APRIL-related disorder. In one embodiment, the subject has or is identified as having a disorder associated with abnormal levels of total IgA. In one embodiment, the subject has or is identified as having a disorder associated with ag IgA (e.g., ag IgAl).

[0153] In one embodiment, the subject has or is identified as having IgA nephropathy (IgAN). In one embodiment, the IgAN is familial IgAN. In one embodiment, the IgAN is adult IgAN. In one embodiment, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0154] In one embodiment, the subject has or is identified as having chronic kidney disease (CKD) or a condition associated with CKD. In one embodiment, the CKD is advanced CKD, e.g., an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0155] In one embodiment, the subject is suffering from or is identified as having Henoch-Schonlein purpura (HSP). In one embodiment, the subject is suffering from or is identified as having cutaneous vasculitis or IgA vasculitis. In one embodiment, the subject is suffering from or is identified as having IgA dermatitis, e.g., IgA bullous dermatosis. In one embodiment, the subject is suffering from or is identified as having Waldenstrom's macroglobulinemia (WM). In one embodiment, the subject is suffering from or is identified as having lupus nephritis.

[0156] In one embodiment, the level of ag IgA in a sample from a subject is determined. In one embodiment, the method further comprises measuring the level of ag IgA in a sample from a subject. In one embodiment, the method further comprises measuring the level of total IgA in the sample. In one embodiment, the method further comprises measuring the level of IgM and / or IgG in the sample. In one embodiment, the method further comprises obtaining a sample from a subject. In one embodiment, the sample is a blood or serum sample.

[0157] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject receives the vaccine before, simultaneously with, or after administration of the anti-APRIL antibody molecule.

[0158] In one embodiment, administration of the anti-APRIL antibody molecule reduces the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%. In one embodiment, administration of the anti-APRIL antibody molecule does not reduce or does not significantly reduce the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine. In one embodiment, a subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to a vaccine following administration of the anti-APRIL antibody molecule.

[0159] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or longer after administration of the anti-APRIL antibody molecule.

[0160] In another aspect, the present disclosure provides a method for selecting a subject for treatment of a condition, the method comprising determining whether administration of an anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA (e.g., a-gIgA1) in a subject in need thereof by at least 40%, thereby selecting the subject. In one embodiment, the level of ag IgA includes the level of a-gIgA1 or the level of ag IgA1.

[0161] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0162] In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% at about 4 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% at about 8 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% at about 12 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% at about 16 weeks after administration of the antibody molecule. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 40% for a predetermined period of time, for example, at least one, two, three or four weeks, or at least one, two or three months. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 50%. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of ag IgA by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In one embodiment, the antibody molecule is administered as a single dose. In one embodiment, the antibody molecule is administered as repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0163] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the ag IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has or is identified as having at least 1,1.5,2,2.5,3.5,4,4.5 or 5 times the total IgA level of a reference subject (e.g., not suffering from the subject of the disease, e.g., healthy or normal subjects). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not yet received or is not receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has or is identified as having the genome susceptibility locus of the disease (e.g., IgA nephropathy). In one embodiment, the method further comprises determining whether the subject has the genome susceptibility locus of the disease (e.g., IgA nephropathy).

[0164] In one embodiment, the subject has or is identified as having an APRIL-related disorder. In one embodiment, the subject has or is identified as having a disorder associated with abnormal levels of total IgA. In one embodiment, the subject has or is identified as having a disorder associated with ag IgA (e.g., ag IgAl).

[0165] In one embodiment, the subject has or is identified as having IgA nephropathy (IgAN). In one embodiment, the IgAN is familial IgAN. In one embodiment, the IgAN is adult IgAN. In one embodiment, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0166] In one embodiment, the subject has or is identified as having chronic kidney disease (CKD) or a condition associated with CKD. In one embodiment, the CKD is advanced CKD, e.g., an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0167] In one embodiment, the subject is suffering from or is identified as having Henoch-Schonlein purpura (HSP). In one embodiment, the subject is suffering from or is identified as having cutaneous vasculitis or IgA vasculitis. In one embodiment, the subject is suffering from or is identified as having IgA dermatitis, e.g., IgA bullous dermatosis. In one embodiment, the subject is suffering from or is identified as having Waldenstrom's macroglobulinemia (WM). In one embodiment, the subject is suffering from or is identified as having lupus nephritis.

[0168] In one embodiment, the level of ag IgA in a sample from a subject is determined. In one embodiment, the method further comprises measuring the level of ag IgA in a sample from a subject. In one embodiment, the method further comprises measuring the level of total IgA in the sample. In one embodiment, the method further comprises measuring the level of IgM and / or IgG in the sample. In one embodiment, the method further comprises obtaining a sample from a subject. In one embodiment, the sample is a blood or serum sample.

[0169] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the anti-APRIL antibody molecule. In one embodiment, the subject receives the vaccine before, simultaneously with, or after administration of the anti-APRIL antibody molecule.

[0170] In one embodiment, administration of the anti-APRIL antibody molecule reduces the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%. In one embodiment, administration of the anti-APRIL antibody molecule does not reduce or does not significantly reduce the ability of a subject to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine. In one embodiment, a subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to a vaccine following administration of the anti-APRIL antibody molecule.

[0171] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or longer after administration of the anti-APRIL antibody molecule.

[0172] In another aspect, the present disclosure provides a method of treating IgA nephropathy, comprising administering an effective amount of an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule described herein) to a subject in need thereof, wherein the subject has received, or will receive, a vaccine (e.g., a vaccine described herein) within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 weeks of administration of the anti-APRIL antibody molecule, thereby treating the IgA nephropathy.

[0173] In one embodiment, the method further comprises administering a vaccine to the subject prior to, concurrently with, or after administration of the anti-APRIL antibody molecule.

[0174] In another aspect, the present disclosure provides a method of vaccinating a subject, the method comprising administering to the subject an effective amount of a vaccine (e.g., a vaccine described herein), wherein the subject has received, or will receive, an anti-APRIL antibody molecule (e.g., an APRIL antibody molecule described herein) within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 weeks of administration of the vaccine, thereby vaccinating the subject.

[0175] In one embodiment, the method further comprises administering to the subject an anti-APRIL antibody molecule prior to, concurrently with, or after administration of the vaccine.

[0176] In yet another aspect, the present disclosure discloses a method of treating a disorder, comprising administering to a subject in need thereof an anti-APRIL antibody molecule, e.g., at a dose or dosage that reduces or may reduce the level of IgM in the subject by at least a predetermined percentage, thereby treating the disorder.

[0177] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0178] In one embodiment, the anti-APRIL antibody molecule reduces or may reduce IgM levels by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In one embodiment, the antibody molecule is administered as a single dose. In one embodiment, the antibody molecule is administered as repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0179] In one embodiment, the subject is a human. In one embodiment, the subject has or is identified as having an IgM level that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the IgM level of a reference subject (e.g., a subject not suffering from the condition, e.g., a healthy or normal subject). In one embodiment, the subject has received or is receiving a different therapeutic agent or treatment modality for the treatment of the condition. In one embodiment, the subject has not yet received or is not receiving a different therapeutic agent or treatment modality for the treatment of the condition.

[0180] In one embodiment, the condition is associated with abnormal levels of IgM. In one embodiment, the condition is chronic kidney disease (CKD) or renal injury. In one embodiment, the condition is fibrosis. In one embodiment, the condition is an IgM-mediated nephropathy, for example, anti-MAG nephropathy or nephropathy associated with anti-GM1. In one embodiment, the condition is systemic lupus erythematosus (SLE). In one embodiment, administration does not reduce, or does not significantly reduce, the level of IgG in the subject. In one embodiment, administration reduces the level of IgG in the subject by no more than a predetermined percentage. In one embodiment, administration reduces the level of IgG in the subject by at least a predetermined percentage.

[0181] In one embodiment, the level of IgM in the sample from the experimenter is determined. In one embodiment, the method also includes determining the level of IgM in the sample from the experimenter. In one embodiment, the method also includes determining the level of total IgM in the sample. In one embodiment, the method also includes determining the level of IgA (e.g., total IgA and / or ag IgA) and / or IgG in the sample. In one embodiment, the level of ag IgA includes the level of ag IgA1 or the level of ag IgA1. In one embodiment, the method also includes obtaining a sample from the experimenter. In one embodiment, the sample is a blood or serum sample.

[0182] In one embodiment, the method further comprises administering to the subject a second therapeutic agent or treatment modality. In one embodiment, the second therapeutic agent or treatment modality is a small molecule. In one embodiment, the second therapeutic agent or treatment modality is an antibody molecule.

[0183] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule. In one embodiment, the subject receives a vaccine before, simultaneously with, or after administration of the antibody molecule.

[0184] In one embodiment, the administration of the antibody molecule reduces the ability of the subject to produce effective antigen-specific serum IgG and / or IgA reactions to the vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or 50%. In one embodiment, the administration of the antibody molecule does not reduce or significantly reduce the ability of the subject to produce effective antigen-specific serum IgG and / or IgA reactions to the vaccine. In one embodiment, the subject has or maintains effective (e.g., protective) antigen-specific serum IgG and / or IgA reactions to the vaccine after administration of the antibody molecule.

[0185] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or more after administration of the antibody molecule.

[0186] In another aspect, the present disclosure discloses a method of reducing the level of IgM in a subject, comprising administering to a subject in need thereof an anti-APRIL antibody molecule, e.g., at a dose or dosage that causes or is likely to cause a reduction in the level of IgM in the subject, thereby reducing the level of IgM.

[0187] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0188] In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of IgM by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%, e.g., over a predetermined period of time. In one embodiment, the antibody molecule is administered as a single dose. In one embodiment, the antibody molecule is administered as repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0189] In one embodiment, the subject is a human. In one embodiment, the subject has or is identified as having an IgM level that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the IgM level of a reference subject (e.g., a subject not suffering from the condition, e.g., a healthy or normal subject). In one embodiment, the subject has received or is receiving a different therapeutic agent or treatment modality for the treatment of the condition. In one embodiment, the subject has not yet received or is not receiving a different therapeutic agent or treatment modality for the treatment of the condition.

[0190] In one embodiment, the condition is associated with abnormal levels of IgM. In one embodiment, the condition is chronic kidney disease (CKD) or renal injury. In one embodiment, the condition is fibrosis. In one embodiment, the condition is an IgM-mediated nephropathy, for example, anti-MAG nephropathy or nephropathy associated with anti-GM1. In one embodiment, the condition is systemic lupus erythematosus (SLE). In one embodiment, administration does not reduce, or does not significantly reduce, the level of IgG in the subject. In one embodiment, administration reduces the level of IgG in the subject by no more than a predetermined percentage. In one embodiment, administration reduces the level of IgG in the subject by at least a predetermined percentage.

[0191] In one embodiment, the level of IgM in the sample from the experimenter is determined. In one embodiment, the method also includes determining the level of IgM in the sample from the experimenter. In one embodiment, the method also includes determining the level of total IgM in the sample. In one embodiment, the method also includes determining the level of IgA (e.g., total IgA and / or ag IgA) and / or IgG in the sample. In one embodiment, the level of ag IgA includes the level of ag IgA1 or the level of ag IgA1. In one embodiment, the method also includes obtaining a sample from the experimenter. In one embodiment, the sample is a blood or serum sample.

[0192] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule. In one embodiment, the subject receives a vaccine before, simultaneously with, or after administration of the antibody molecule.

[0193] In one embodiment, the administration of the antibody molecule reduces the ability of the subject to produce effective antigen-specific serum IgG and / or IgA reactions to the vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or 50%. In one embodiment, the administration of the antibody molecule does not reduce or significantly reduce the ability of the subject to produce effective antigen-specific serum IgG and / or IgA reactions to the vaccine. In one embodiment, the subject has or maintains effective (e.g., protective) antigen-specific serum IgG and / or IgA reactions to the vaccine after administration of the antibody molecule.

[0194] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or more after administration of the antibody molecule.

[0195] In another aspect, the disclosure provides a method of treating a disorder, comprising administering to a subject in need thereof an anti-APRIL antibody molecule, e.g., at a dose or dosage that reduces or is likely to reduce the levels of IgA and IgM in the subject by at least a predetermined percentage, thereby treating the disorder.

[0196] In one embodiment, the level of IgA includes, or is, the level of total IgA and / or ag IgA. In one embodiment, the level of ag IgA includes, or is, the level of ag IgAl.

[0197] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0198] In one embodiment, administration does not reduce, or does not significantly reduce, the level of IgG in a subject. In one embodiment, administration reduces the level of IgG in a subject by no more than a predetermined percentage. In one embodiment, administration reduces the level of IgG in a subject by at least a predetermined percentage.

[0199] In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%, e.g., over a predetermined period of time. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of total IgA by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%, e.g., over a predetermined period of time. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of IgM by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%, e.g., over a predetermined period of time. In one embodiment, the anti-APRIL antibody molecule reduces or is likely to reduce the level of IgA (e.g., total and / or ag IgA) by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%, and reduces or is likely to reduce the level of IgM by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%, e.g., over a predetermined period of time. In one embodiment, the antibody molecule is administered in a single dose. In one embodiment, the antibody molecule is administered in repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0200] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5 or 5 times the ag IgA level of a reference subject (e.g., a subject not suffering from the disease, e.g., a healthy or normal subject). In one embodiment, the subject has or is identified as having at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5 or 5 times the total IgA level of a reference subject (e.g., a subject not suffering from the disease, e.g., a healthy or normal subject). In one embodiment, the subject has or is identified as having at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5 or 5 times the total IgA level of a reference subject (e.g., a subject not suffering from the disease, e.g., a healthy or normal subject). In one embodiment, the subject has or is identified as having at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5 or 5 times the IgM level of ag IgM level of a reference subject (e.g., a subject not suffering from the disease, e.g., a healthy or normal subject). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not received or is not currently receiving a different therapeutic agent or treatment modality for treating the disorder.

[0201] In one embodiment, the disease is an APRIL-related disease. In one embodiment, the disease is associated with abnormal levels of IgA (e.g., total IgA and / or ag IgA) and / or IgM, e.g., diseases as described herein. In one embodiment, the disease is systemic lupus erythematosus (SLE). In one embodiment, administration does not reduce, or does not significantly reduce, the level of the IgG of the subject. In one embodiment, administration reduces the level of the IgG of the subject by no more than a predetermined percentage. In one embodiment, administration reduces the level of IgG in the subject by at least a predetermined percentage. In one embodiment, the level of IgA and / or IgM (and optionally IgG) in the sample from the subject is determined. In one embodiment, the method further comprises determining the level of ag IgA in the sample from the subject. In one embodiment, the method further comprises determining the level of total IgA in the sample. In one embodiment, the method further comprises determining the level of IgM in the sample. In one embodiment, the method further comprises determining the level of IgG in the sample. In one embodiment, the method further comprises obtaining a sample from the subject. In one embodiment, the sample is a blood or serum sample.

[0202] In one embodiment, the method further comprises administering to the subject a second therapeutic agent or treatment modality. In one embodiment, the second therapeutic agent or treatment modality is a small molecule. In one embodiment, the second therapeutic agent or treatment modality is an antibody molecule.

[0203] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule. In one embodiment, the subject receives a vaccine before, simultaneously with, or after administration of the antibody molecule.

[0204] In one embodiment, the administration of the antibody molecule reduces the ability of the subject to produce effective antigen-specific serum IgG and / or IgA reactions to the vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or 50%. In one embodiment, the administration of the antibody molecule does not reduce or significantly reduce the ability of the subject to produce effective antigen-specific serum IgG and / or IgA reactions to the vaccine. In one embodiment, the subject has or maintains effective (e.g., protective) antigen-specific serum IgG and / or IgA reactions to the vaccine after administration of the antibody molecule.

[0205] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or more after administration of the antibody molecule.

[0206] In yet another aspect, the present disclosure provides a method of reducing the levels of IgA and IgM in a subject, the method comprising administering to a subject in need thereof an anti-APRIL antibody molecule, e.g., at a dose or dosage that reduces or is likely to reduce the levels of IgA and IgM in the subject by a predetermined percentage, thereby reducing the levels of IgA and IgM.

[0207] In one embodiment, the level of IgA includes, or is, the level of total IgA and / or ag IgA. In one embodiment, the level of ag IgA includes, or is, the level of ag IgAl.

[0208] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0209] In one embodiment, administration does not reduce, or does not significantly reduce, the level of IgG in a subject. In one embodiment, administration reduces the level of IgG in a subject by no more than a predetermined percentage. In one embodiment, administration reduces the level of IgG in a subject by at least a predetermined percentage.

[0210] In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%, e.g., over a predetermined period of time. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of total IgA by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%, e.g., over a predetermined period of time. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of IgM by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%, e.g., over a predetermined period of time. In one embodiment, the anti-APRIL antibody molecule reduces or is likely to reduce the level of IgA (e.g., total and / or ag IgA) by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%, and reduces or is likely to reduce the level of IgM by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%, e.g., over a predetermined period of time. In one embodiment, the antibody molecule is administered in a single dose. In one embodiment, the antibody molecule is administered in repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0211] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5 or 5 times the ag IgA level of a reference subject (e.g., a subject not suffering from the disease, e.g., a healthy or normal subject). In one embodiment, the subject has or is identified as having at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5 or 5 times the total IgA level of a reference subject (e.g., a subject not suffering from the disease, e.g., a healthy or normal subject). In one embodiment, the subject has or is identified as having at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5 or 5 times the total IgA level of a reference subject (e.g., a subject not suffering from the disease, e.g., a healthy or normal subject). In one embodiment, the subject has or is identified as having at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5 or 5 times the IgM level of ag IgM level of a reference subject (e.g., a subject not suffering from the disease, e.g., a healthy or normal subject). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not received or is not currently receiving a different therapeutic agent or treatment modality for treating the disorder.

[0212] In one embodiment, the disease is an APRIL-related disease. In one embodiment, the disease is associated with abnormal levels of IgA (e.g., total IgA and / or ag IgA) and / or IgM, e.g., diseases as described herein. In one embodiment, the disease is systemic lupus erythematosus (SLE). In one embodiment, administration does not reduce, or does not significantly reduce, the level of the IgG of the subject. In one embodiment, administration reduces the level of the IgG of the subject by no more than a predetermined percentage. In one embodiment, administration reduces the level of IgG in the subject by at least a predetermined percentage. In one embodiment, the level of IgA and / or IgM (and optionally IgG) in the sample from the subject is determined. In one embodiment, the method further comprises determining the level of ag IgA in the sample from the subject. In one embodiment, the method further comprises determining the level of total IgA in the sample. In one embodiment, the method further comprises determining the level of IgM in the sample. In one embodiment, the method further comprises determining the level of IgG in the sample. In one embodiment, the method further comprises obtaining a sample from the subject. In one embodiment, the sample is a blood or serum sample.

[0213] In one embodiment, the method further comprises administering to the subject a second therapeutic agent or treatment modality. In one embodiment, the second therapeutic agent or treatment modality is a small molecule. In one embodiment, the second therapeutic agent or treatment modality is an antibody molecule.

[0214] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule. In one embodiment, the subject receives a vaccine before, simultaneously with, or after administration of the antibody molecule.

[0215] In one embodiment, the administration of the antibody molecule reduces the ability of the subject to produce effective antigen-specific serum IgG and / or IgA reactions to the vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or 50%. In one embodiment, the administration of the antibody molecule does not reduce or significantly reduce the ability of the subject to produce effective antigen-specific serum IgG and / or IgA reactions to the vaccine. In one embodiment, the subject has or maintains effective (e.g., protective) antigen-specific serum IgG and / or IgA reactions to the vaccine after administration of the antibody molecule.

[0216] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or more after administration of the antibody molecule.

[0217] In another aspect, the disclosure provides a method of treating a disorder, the method comprising administering to a subject in need thereof an effective amount of an anti-APRIL antibody molecule, wherein the disorder is:

[0218] (a) advanced chronic kidney disease (CKD) (e.g., eGFR equal to or greater than about 30 or 45);

[0219] (b) post-transplant IgAN;

[0220] (c) Pediatric IgAN;

[0221] (d) Henoch-Schönlein purpura (HSP) or cutaneous vasculitis;

[0222] (e) IgAN with crescentic glomerulonephritis (GN);

[0223] (f) IgA vasculitis;

[0224] (g) IgA dermatitis;

[0225] (h) IgM-mediated neuropathy (anti-MAG or anti-GM1);

[0226] (i) Waldenstrom's macroglobulinemia (WM); or

[0227] (j) Lupus nephritis.

[0228] In one embodiment, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In one embodiment, the anti-APRIL antibody molecule comprises 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, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237. In one embodiment, the anti-APRIL antibody molecule comprises 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, The VH and VL of any one of 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.

[0229] In one embodiment, administration causes or may cause a decrease in IgA in a subject. In one embodiment, administration causes or may cause a decrease in IgM in a subject. In one embodiment, the level of IgA includes, or is the level of total IgA and / or a-g IgA. In one embodiment, the level of ag IgA includes, or is the level of ag IgA1.

[0230] In one embodiment, administration does not reduce, or does not significantly reduce, the level of IgG in a subject. In one embodiment, administration reduces the level of IgG in a subject by no more than a predetermined percentage. In one embodiment, administration reduces the level of IgG in a subject by at least a predetermined percentage.

[0231] In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of a-g IgA by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%, e.g., over a predetermined period of time. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of total IgA by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%, e.g., over a predetermined period of time. In one embodiment, the anti-APRIL antibody molecule reduces or may reduce the level of IgM by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%, e.g., over a predetermined period of time. In one embodiment, the anti-APRIL antibody molecule reduces or is likely to reduce the level of IgA (e.g., total and / or ag IgA) by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%, and reduces or is likely to reduce the level of IgM by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%, e.g., over a predetermined period of time. In one embodiment, the antibody molecule is administered in a single dose. In one embodiment, the antibody molecule is administered in repeated doses. In one embodiment, the antibody molecule is administered subcutaneously. In one embodiment, the antibody molecule is administered intravenously.

[0232] In one embodiment, the subject is a person. In one embodiment, the subject has or is identified as having at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5 or 5 times the ag IgA level of a reference subject (e.g., a subject not suffering from the disease, e.g., a healthy or normal subject). In one embodiment, the subject has or is identified as having at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5 or 5 times the total IgA level of a reference subject (e.g., a subject not suffering from the disease, e.g., a healthy or normal subject). In one embodiment, the subject has or is identified as having at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5 or 5 times the total IgA level of a reference subject (e.g., a subject not suffering from the disease, e.g., a healthy or normal subject). In one embodiment, the subject has or is identified as having at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5 or 5 times the IgM level of ag IgM level of a reference subject (e.g., a subject not suffering from the disease, e.g., a healthy or normal subject). In one embodiment, the subject has received or is receiving different therapeutic agents or treatment modalities for the treatment of the disease. In one embodiment, the subject has not received or is not currently receiving a different therapeutic agent or treatment modality for treating the disorder.

[0233] In one embodiment, the condition is advanced chronic kidney disease (CKD) (e.g., eGFR equal to or greater than about 30 or 45). In one embodiment, the condition is post-transplant IgAN. In one embodiment, the condition is pediatric IgAN. In one embodiment, the condition is Henoch-Schönlein purpura (HSP) or cutaneous vasculitis. In one embodiment, the condition is IgAN with crescentic glomerulonephritis (GN). In one embodiment, the condition is IgA vasculitis. In one embodiment, the condition is IgA dermatitis. In one embodiment, the condition is IgM-mediated nephropathy (anti-MAG or anti-GM1). In one embodiment, the condition is Waldenstrom's macroglobulinemia (WM). In one embodiment, the condition is lupus nephritis.

[0234] In one embodiment, the method further comprises administering to the subject a second therapeutic agent or treatment modality. In one embodiment, the second therapeutic agent or treatment modality is a small molecule. In one embodiment, the second therapeutic agent or treatment modality is an antibody molecule.

[0235] In one embodiment, the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule. In one embodiment, the subject is in need of or identified as in need of a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule. In one embodiment, the subject receives a vaccine before, simultaneously with, or after administration of the antibody molecule.

[0236] In one embodiment, the administration of the antibody molecule reduces the ability of the subject to produce effective antigen-specific serum IgG and / or IgA reactions to the vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or 50%. In one embodiment, the administration of the antibody molecule does not reduce or significantly reduce the ability of the subject to produce effective antigen-specific serum IgG and / or IgA reactions to the vaccine. In one embodiment, the subject has or maintains effective (e.g., protective) antigen-specific serum IgG and / or IgA reactions to the vaccine after administration of the antibody molecule.

[0237] In one embodiment, the vaccine includes tetanus toxoid, diphtheria toxoid, or both (e.g., In one embodiment, the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or more after administration of the antibody molecule.

[0238] In another aspect, the present disclosure provides a method of treating a disorder associated with an autoantigen, the method comprising administering to a subject in need thereof an effective amount of a therapeutic agent or treatment modality, wherein administration reduces or may reduce the level of the autoantigen in the subject by at least a predetermined percentage.

[0239] In one embodiment, the subject is a human.In one embodiment, the subject has or is identified as having an APRIL-associated disorder.

[0240] In one embodiment, the level of the autoantigen in a sample from the subject is determined. In one embodiment, the method further comprises obtaining a sample from the subject. In one embodiment, the sample is a blood or serum sample.

[0241] In one embodiment, the method further comprises administering to the subject a second therapeutic agent or treatment modality. In one embodiment, the second therapeutic agent or treatment modality is a small molecule. In one embodiment, the second therapeutic agent or treatment modality is an antibody molecule.

[0242] In one aspect, the present disclosure provides a method of treating IgA nephropathy, the method comprising:

[0243] In response to identifying a subject who would benefit from administration of an anti-APRIL antibody molecule, administering to the subject an effective amount of the anti-APRIL antibody molecule,

[0244] wherein the anti-APRIL antibody molecule is administered no more than once a month,

[0245] The benefits include one or more (e.g., two, three, or all) of the following:

[0246] (i) APRIL levels are reduced by 90% or more within one month of administration of the anti-APRIL antibody molecule, compared to the subject's baseline APRIL levels;

[0247] (ii) a 60% or greater decrease in galactose-deficient IgA1 (Gd-IgA1) level within nine months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline Gd-IgA level;

[0248] (iii) a 30% or greater decrease in 24-hour urine protein to creatinine ratio (uPCR) within nine months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline uPCR; or

[0249] (iv) maintaining (e.g., maintaining or increasing) mean eGFR over a period of at least 12 months after administration of the anti-APRIL antibody molecule, compared to the subject's baseline eGFR,

[0250] Thereby treating IgA nephropathy.

[0251] In one embodiment, the anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and

[0252] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0253] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0254] In one embodiment, the subject's baseline APRIL level is the APRIL level before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In one embodiment, the subject's baseline Gd-IgA level is the Gd-IgA level before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In one embodiment, the subject's baseline uPCR is the uPCR before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In one embodiment, the subject's baseline eGFR is the eGFR before administration of the anti-APRIL antibody molecule (e.g., before the first administration).

[0255] In one embodiment, the method further comprises identifying a subject who would benefit from administration of the anti-APRIL antibody molecule.

[0256] In one embodiment, the benefit comprises: (ii) a 60% or greater reduction in the level of galactose-deficient IgA1 (Gd-IgA1) within nine months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline Gd-IgA level; and (iv) maintaining (e.g., maintaining or increasing) the mean eGFR over a period of at least 12 months after administration of the anti-APRIL antibody molecule, compared to the subject's baseline eGFR.

[0257] In one embodiment, APRIL levels are reduced by 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more within one month of administration of the anti-APRIL antibody molecule, compared to the subject's baseline APRIL levels. In one embodiment, Gd-IgA1 levels are reduced by 65%, 70%, 75%, 85%, 90%, 95% or more within nine months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline Gd-IgA levels. In one embodiment, 24-hour uPCR is reduced by 35%, 40%, 45%, 50%, 55%, 60% or more within nine months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline uPCR. In one embodiment, the mean eGFR is maintained (e.g., maintained or increased) over a period of at least 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 months compared to the subject's baseline eGFR.

[0258] In one embodiment, the benefit further comprises: (v) a decrease in IgG levels compared to the subject's baseline IgG levels, optionally wherein the IgG levels are anti-gd-IgA1 IgG levels. In one embodiment, the benefit further comprises: (vi) a decrease in IgA levels compared to the subject's baseline IgA levels. In one embodiment, the benefit further comprises: (vii) a ratio of the average eGFR over a period of 12 months following administration of the anti-APRIL antibody molecule to the expected average eGFR over a period of 12 months if the anti-APRIL antibody molecule were not administered to the subject of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. In one embodiment, the benefit further comprises: (vii) the eGFR does not decrease by 5%, 10%, 15%, or more within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline eGFR.

[0259] In one embodiment, the subject has one or more (e.g., two or all) of the following prior to administration of the anti-APRIL antibody molecule: (a) receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) for at least three months; (b) uPCR greater than 0.75 g / g or a 24-hour urine protein (UP) level greater than 1.0 g / d; or (c) eGFR greater than 30 mL / min / 1.73 m 2 In one embodiment, the subject has one or both of the following prior to administration of the anti-APRIL antibody molecule: (a) a proteinuria level greater than 2.0 g / day; or (b) an eGFR equal to or less than 60 mL / min / 1.73 m 2 .

[0260] In one embodiment, the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the anti-APRIL antibody molecule comprises a VL comprising the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO: 286. In one embodiment, the anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of K. In one embodiment, the anti-APRIL antibody molecule is sibeprenlimab.

[0261] In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered once a month, once every two months, once every three months or once every six months. In one embodiment, the anti-APRIL antibody molecule is administered repeatedly, for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 times. In one embodiment, the anti-APRIL antibody molecule is administered once a month for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months. In one embodiment, the anti-APRIL antibody molecule is administered intravenously or subcutaneously. In one embodiment, the anti-APRIL antibody molecule is administered intravenously. In one embodiment, the anti-APRIL antibody molecule is administered subcutaneously.

[0262] In one aspect, the present disclosure provides a method for treating IgA nephropathy, comprising administering to a subject in need thereof an effective amount of an anti-APRIL antibody molecule,

[0263] wherein the anti-APRIL antibody molecule is administered no more than once a month,

[0264] wherein the administering results in one or more (e.g., two, three, or all) of the following:

[0265] (i) APRIL levels are reduced by 90% or more within one month of administration of the anti-APRIL antibody molecule, compared to the subject's baseline APRIL levels;

[0266] (ii) a 60% or greater decrease in galactose-deficient IgA1 (Gd-IgA1) level within nine months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline Gd-IgA level;

[0267] (iii) a 30% or greater decrease in 24-hour urine protein to creatinine ratio (uPCR) within nine months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline uPCR; or

[0268] (iv) maintaining (e.g., maintaining or increasing) mean eGFR over a period of at least 12 months after administration of the anti-APRIL antibody molecule, compared to the subject's baseline eGFR,

[0269] Thereby treating IgA nephropathy.

[0270] In one embodiment, the anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and

[0271] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0272] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0273] In one embodiment, the subject's baseline APRIL level is the APRIL level before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In one embodiment, the subject's baseline Gd-IgA level is the Gd-IgA level before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In one embodiment, the subject's baseline uPCR is the uPCR before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In one embodiment, the subject's baseline eGFR is the eGFR before administration of the anti-APRIL antibody molecule (e.g., before the first administration).

[0274] In one embodiment, the benefit comprises or the administration results in: (ii) a 60% or greater reduction in the level of galactose-deficient IgA1 (Gd-IgA1) within nine months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline Gd-IgA level; and (iv) maintaining (e.g., maintaining or increasing) the mean eGFR for a period of at least 12 months after administration of the anti-APRIL antibody molecule, compared to the subject's baseline eGFR.

[0275] In one embodiment, APRIL levels are reduced by 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more within one month of administration of the anti-APRIL antibody molecule, compared to the subject's baseline APRIL levels. In one embodiment, Gd-IgA1 levels are reduced by 65%, 70%, 75%, 85%, 90%, 95% or more within nine months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline Gd-IgA levels. In one embodiment, 24-hour uPCR is reduced by 35%, 40%, 45%, 50%, 55%, 60% or more within nine months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline uPCR. In one embodiment, the mean eGFR is maintained (e.g., maintained or increased) over a period of at least 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 months compared to the subject's baseline eGFR.

[0276] In one embodiment, administration further results in: (v) a decrease in IgG levels compared to the subject's baseline IgG levels, optionally wherein the IgG levels are anti-gd-IgA1 IgG levels. In one embodiment, administration further results in: (vi) a decrease in IgA levels compared to the subject's baseline IgA levels. In one embodiment, administration further results in: (vii) a ratio of the average eGFR over a period of 12 months following administration of the anti-APRIL antibody molecule to the expected average eGFR over a period of 12 months if the anti-APRIL antibody molecule had not been administered to the subject of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. In one embodiment, administration further results in: (vii) eGFR does not decrease by 5%, 10%, 15%, or more within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline eGFR.

[0277] In one embodiment, the subject has one or more (e.g., two or all) of the following prior to administration of the anti-APRIL antibody molecule: (a) receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) for at least three months; (b) uPCR greater than 0.75 g / g or a 24-hour urine protein (UP) level greater than 1.0 g / d; or (c) eGFR greater than 30 mL / min / 1.73 m 2 In one embodiment, the subject has one or both of the following prior to administration of the anti-APRIL antibody molecule: (a) a proteinuria level greater than 2.0 g / day; or (b) an eGFR equal to or less than 60 mL / min / 1.73 m 2 .

[0278] In one embodiment, the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the anti-APRIL antibody molecule comprises a VL comprising the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO: 286. In one embodiment, the anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of Kappa. In one embodiment, the anti-APRIL antibody molecule is siberryizumab.

[0279] In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered once a month, once every two months, once every three months or once every six months. In one embodiment, the anti-APRIL antibody molecule is administered repeatedly, for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 times. In one embodiment, the anti-APRIL antibody molecule is administered once a month for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months. In one embodiment, the anti-APRIL antibody molecule is administered intravenously or subcutaneously. In one embodiment, the anti-APRIL antibody molecule is administered intravenously. In one embodiment, the anti-APRIL antibody molecule is administered subcutaneously.

[0280] In one aspect, the present disclosure provides a method for treating IgA nephropathy, comprising administering to a subject in need thereof an effective amount of an anti-APRIL antibody molecule,

[0281] wherein the subject has or is identified as having: (a) a proteinuria level greater than 2.0 g / day, (b) an estimated glomerular filtration rate (eGFR) less than 60 mL / min / 1.73 m 2 or (c) both (a) and (b),

[0282] Optionally wherein the anti-APRIL antibody molecule is administered no more than once per month,

[0283] Thereby treating IgA nephropathy.

[0284] In one embodiment, the anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and

[0285] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0286] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0287] In one embodiment, the anti-APRIL antibody molecule is administered in response to identification of a subject with: (a) a proteinuria level greater than 2.0 g / day, (b) an estimated glomerular filtration rate (eGFR) less than 60 mL / min / 1.73 m 2 or (c) both (a) and (b).

[0288] In one embodiment, the method further comprises identifying a subject having: (a) a proteinuria level greater than 2.0 g / day, (b) an estimated glomerular filtration rate (eGFR) less than 60 mL / min / 1.73 m 2 or (c) both (a) and (b).

[0289] In one embodiment, the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the anti-APRIL antibody molecule comprises a VL comprising the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO: 286. In one embodiment, the anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of Kappa. In one embodiment, the anti-APRIL antibody molecule is siberryizumab.

[0290] In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered once a month, once every two months, once every three months or once every six months. In one embodiment, the anti-APRIL antibody molecule is administered repeatedly, for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 times. In one embodiment, the anti-APRIL antibody molecule is administered once a month for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months. In one embodiment, the anti-APRIL antibody molecule is administered intravenously or subcutaneously. In one embodiment, the anti-APRIL antibody molecule is administered intravenously. In one embodiment, the anti-APRIL antibody molecule is administered subcutaneously.

[0291] In one aspect, the present disclosure provides a method of treating IgA nephropathy, comprising administering to a subject in need thereof an effective amount of a second anti-APRIL antibody molecule,

[0292] wherein said subject has been administered a first anti-APRIL antibody molecule at a dose of at least 600 mg once every two weeks, and said administration of said first anti-APRIL antibody is discontinued,

[0293] wherein the second anti-APRIL antibody molecule is administered no more than once a month,

[0294] Thereby treating IgA nephropathy.

[0295] In some embodiments, the second anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and

[0296] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0297] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0298] In one embodiment, in response to identifying a subject that has been administered a first anti-APRIL antibody molecule at a dose of at least 600 mg biweekly, administration of the first anti-APRIL antibody molecule is discontinued and the second anti-APRIL antibody molecule is administered.

[0299] In one embodiment, the method further comprises: (a) identifying a subject who has been administered the first anti-APRIL antibody molecule at a dose of at least 600 mg biweekly; and (b) ceasing administration of the first anti-APRIL antibody molecule.

[0300] In one embodiment, the second anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the second anti-APRIL antibody molecule comprises a VL comprising the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the second antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO: 286. In one embodiment, the second anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of Kappa. In one embodiment, the second anti-APRIL antibody molecule is siberryizumab.

[0301] In one embodiment, the second anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg. In one embodiment, the second anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In one embodiment, the second anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In one embodiment, the second anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In one embodiment, the second anti-APRIL antibody molecule is administered once a month, once every two months, once every three months or once every six months. In one embodiment, the second anti-APRIL antibody molecule is administered repeatedly, for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 times. In one embodiment, the second anti-APRIL antibody molecule is administered once a month for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months. In one embodiment, the second anti-APRIL antibody molecule is administered intravenously or subcutaneously. In one embodiment, the second anti-APRIL antibody molecule is administered intravenously. In one embodiment, the second anti-APRIL antibody molecule is administered subcutaneously.

[0302] In one embodiment, the first anti-APRIL antibody molecule is BION-1301 or any one of the anti-APRIL antibody molecules disclosed in WO2010 / 100056, WO2015 / 034364, WO2016 / 110587 and WO2021 / 243298.

[0303] In one aspect, the present disclosure provides a method of treating IgA nephropathy, comprising administering a second anti-APRIL antibody molecule to a subject in need thereof at a dose of at least 600 mg once every two weeks,

[0304] wherein a first anti-APRIL antibody molecule has been administered to said subject, and said administration of said first anti-APRIL antibody molecule is stopped,

[0305] Thereby treating IgA nephropathy.

[0306] In some embodiments, the first anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and

[0307] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0308] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0309] In one embodiment, the second anti-APRIL antibody molecule is administered in response to recognition of a subject to which the first anti-APRIL antibody molecule has been administered.

[0310] In one embodiment, the method further comprises: (a) identifying a subject to whom the first anti-APRIL antibody molecule has been administered; and (b) ceasing administration of the first anti-APRIL antibody molecule.

[0311] In one embodiment, the first anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the first anti-APRIL antibody molecule comprises a VL comprising the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the first antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO: 286. In one embodiment, the first anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of Kappa. In one embodiment, the first anti-APRIL antibody molecule is siberryizumab.

[0312] In one embodiment, the first anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg, or 8 mg / kg. In one embodiment, the first anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In one embodiment, the first anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In one embodiment, the first anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In one embodiment, the first anti-APRIL antibody molecule is administered once a month, once every two months, once every three months, or once every six months. In one embodiment, the first anti-APRIL antibody molecule is administered repeatedly, for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 times. In one embodiment, the first anti-APRIL antibody molecule is administered once a month for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months. In one embodiment, the first anti-APRIL antibody molecule is administered intravenously or subcutaneously. In one embodiment, the first anti-APRIL antibody molecule is administered intravenously. In one embodiment, the first anti-APRIL antibody molecule is administered subcutaneously.

[0313] In one embodiment, the second anti-APRIL antibody molecule is BION-1301 or any one of the anti-APRIL antibody molecules disclosed in WO2010 / 100056, WO2015 / 034364, WO2016 / 110587 and WO2021 / 243298.

[0314] In one aspect, the present disclosure provides a method for treating IgA nephropathy, comprising administering to a subject in need thereof an effective amount of an anti-APRIL antibody molecule,

[0315] wherein the subject has been administered: (i) budesonide (e.g., at a dose of 16 mg once daily), (ii) atrasentan (e.g., at a dose of 0.75 mg once daily), (iii) dapagliflozin (e.g., at a dose of 5 mg or 10 mg once daily); or (iv) methylprednisolone (e.g., once daily), and the administration of (i) budesonide, (ii) atrasentan, (iii) dapagliflozin, or (iv) methylprednisolone is discontinued,

[0316] wherein the anti-APRIL antibody molecule is administered no more than once a month,

[0317] Thereby treating IgA nephropathy.

[0318] In some embodiments, the anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and

[0319] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0320] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0321] In one embodiment, the anti-APRIL antibody molecule is administered in response to recognition of a subject who has been administered (i) budesonide (e.g., at a dose of 16 mg once daily), (ii) atrasentan (e.g., at a dose of 0.75 mg once daily), (iii) dapagliflozin (e.g., at a dose of 5 mg or 10 mg once daily); or (iv) methylprednisolone (e.g., once daily).

[0322] In one embodiment, the method further comprises: (a) identifying a subject who has been administered (i) budesonide (e.g., at a dose of 16 mg once daily), (ii) atrasentan (e.g., at a dose of 0.75 mg once daily), (iii) dapagliflozin (e.g., at a dose of 5 mg or 10 mg once daily); or (iv) methylprednisolone (e.g., once daily); and (b) discontinuing administration of (i) budesonide, (ii) atrasentan, (iii) dapagliflozin, or (iv) methylprednisolone.

[0323] In one embodiment, the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the anti-APRIL antibody molecule comprises a VL comprising the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO: 286. In one embodiment, the anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of Kappa. In one embodiment, the anti-APRIL antibody molecule is siberryizumab.

[0324] In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered once a month, once every two months, once every three months or once every six months. In one embodiment, the anti-APRIL antibody molecule is administered repeatedly, for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 times. In one embodiment, the anti-APRIL antibody molecule is administered once a month for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months. In one embodiment, the anti-APRIL antibody molecule is administered intravenously or subcutaneously. In one embodiment, the anti-APRIL antibody molecule is administered intravenously. In one embodiment, the anti-APRIL antibody molecule is administered subcutaneously.

[0325] In one aspect, the present disclosure provides a method of treating IgA nephropathy, comprising administering to a subject in need thereof (i) budesonide (e.g., at a dose of 16 mg once daily), (ii) atrasentan (e.g., at a dose of 0.75 mg once daily), (iii) dapagliflozin (e.g., at a dose of 5 mg or 10 mg once daily); or (iv) methylprednisolone (e.g., once daily),

[0326] wherein said subject has been administered an anti-APRIL antibody molecule, and said administration of said anti-APRIL antibody molecule is stopped,

[0327] Thereby treating IgA nephropathy.

[0328] In some embodiments, the first anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and

[0329] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0330] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0331] In one embodiment, (i) budesonide, (ii) atrasentan, (iii) dapagliflozin, or (iv) methylprednisolone is administered in response to recognition of a subject to which the anti-APRIL antibody molecule has been administered.

[0332] In one embodiment, the method further comprises: (a) identifying a subject to whom the anti-APRIL antibody molecule has been administered; (b) ceasing administration of the anti-APRIL antibody molecule.

[0333] In one embodiment, the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the anti-APRIL antibody molecule comprises a VL comprising the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO: 286. In one embodiment, the anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of Kappa. In one embodiment, the anti-APRIL antibody molecule is siberryizumab.

[0334] In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered once a month, once every two months, once every three months or once every six months. In one embodiment, the anti-APRIL antibody molecule is administered repeatedly, for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 times. In one embodiment, the anti-APRIL antibody molecule is administered once a month for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months. In one embodiment, the anti-APRIL antibody molecule is administered intravenously or subcutaneously. In one embodiment, the anti-APRIL antibody molecule is administered intravenously. In one embodiment, the anti-APRIL antibody molecule is administered subcutaneously.

[0335] In one aspect, the present disclosure provides a method of selecting a subject for treatment comprising an anti-APRIL antibody molecule, the method comprising:

[0336] (a) determining whether a subject develops one or more (e.g., two, three, or all) of the following after administration of the anti-APRIL antibody molecule:

[0337] (i) APRIL levels are reduced by 90% or more within one month of administration of the anti-APRIL antibody molecule, compared to the subject's baseline APRIL levels;

[0338] (ii) a 60% or greater decrease in galactose-deficient IgA1 (Gd-IgA1) level within nine months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline Gd-IgA level;

[0339] (iii) a 30% or greater decrease in 24-hour urine protein to creatinine ratio (uPCR) within nine months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline uPCR; or

[0340] (iv) maintaining (e.g., maintaining or increasing) mean eGFR over a period of at least 12 months after administration of the anti-APRIL antibody molecule, compared to the subject's baseline eGFR;

[0341] (b) selecting the subject based on determining that the subject will experience one or more (e.g., two, three, or all) of (i), (ii), (iii), or (iv) following administration of the anti-APRIL antibody molecule,

[0342] wherein the anti-APRIL antibody molecule is to be administered no more than once a month,

[0343] wherein the subject has or is at risk of developing IgA nephropathy,

[0344] Thus, the subjects were selected.

[0345] In one embodiment, the anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and

[0346] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0347] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0348] In one embodiment, the subject's baseline APRIL level is the APRIL level before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In one embodiment, the subject's baseline Gd-IgA level is the Gd-IgA level before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In one embodiment, the subject's baseline uPCR is the uPCR before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In one embodiment, the subject's baseline eGFR is the eGFR before administration of the anti-APRIL antibody molecule (e.g., before the first administration).

[0349] In one embodiment, determining whether a subject will have one or more (e.g., two, three, or all) of (i), (ii), (iii), or (iv) following administration of the anti-APRIL antibody molecule is based at least in part on the studies described in Example 10.

[0350] In one embodiment, the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the anti-APRIL antibody molecule comprises a VL comprising the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO: 286. In one embodiment, the anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of Kappa. In one embodiment, the anti-APRIL antibody molecule is siberryizumab.

[0351] In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered once a month, once every two months, once every three months or once every six months. In one embodiment, the anti-APRIL antibody molecule is administered repeatedly, for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 times. In one embodiment, the anti-APRIL antibody molecule is to be administered once a month for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months. In one embodiment, the anti-APRIL antibody molecule is to be administered intravenously or subcutaneously. In one embodiment, the anti-APRIL antibody molecule is to be administered intravenously. In one embodiment, the anti-APRIL antibody molecule is to be administered subcutaneously. In one embodiment, the method further comprises administering the anti-APRIL antibody molecule to the subject.

[0352] In one aspect, the present disclosure provides a method of selecting a therapy comprising an anti-APRIL antibody molecule for a subject, the method comprising:

[0353] (a) determining whether a subject develops one or more (e.g., two, three, or all) of the following after administration of the anti-APRIL antibody molecule:

[0354] (i) APRIL levels are reduced by 90% or more within one month of administration of the anti-APRIL antibody molecule, compared to the subject's baseline APRIL levels;

[0355] (ii) a 60% or greater decrease in galactose-deficient IgA1 (Gd-IgA1) level within nine months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline Gd-IgA level;

[0356] (iii) a 30% or greater decrease in 24-hour urine protein to creatinine ratio (uPCR) within nine months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline uPCR; or

[0357] (iv) maintaining (e.g., maintaining or increasing) mean eGFR over a period of at least 12 months after administration of the anti-APRIL antibody molecule, compared to the subject's baseline eGFR;

[0358] (b) selecting the therapy comprising the anti-APRIL antibody molecule based on determining that the subject will experience one or more (e.g., two, three, or all) of (i), (ii), (iii), or (iv) following administration of the anti-APRIL antibody molecule,

[0359] wherein the anti-APRIL antibody molecule is administered no more than once a month,

[0360] wherein the subject has or is at risk of developing IgA nephropathy,

[0361] Thus choosing a therapy.

[0362] In one embodiment, the anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and

[0363] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0364] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0365] In one embodiment, the subject's baseline APRIL level is the APRIL level before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In one embodiment, the subject's baseline Gd-IgA level is the Gd-IgA level before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In one embodiment, the subject's baseline uPCR is the uPCR before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In one embodiment, the subject's baseline eGFR is the eGFR before administration of the anti-APRIL antibody molecule (e.g., before the first administration).

[0366] In one embodiment, determining whether a subject will have one or more (e.g., two, three, or all) of (i), (ii), (iii), or (iv) following administration of the anti-APRIL antibody molecule is based at least in part on the studies described in Example 10.

[0367] In one embodiment, the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the anti-APRIL antibody molecule comprises a VL comprising the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In one embodiment, the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO: 286. In one embodiment, the anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of Kappa. In one embodiment, the anti-APRIL antibody molecule is siberryizumab.

[0368] In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In one embodiment, the anti-APRIL antibody molecule is administered once a month, once every two months, once every three months or once every six months. In one embodiment, the anti-APRIL antibody molecule is administered repeatedly, for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 times. In one embodiment, the anti-APRIL antibody molecule is to be administered once a month for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months. In one embodiment, the anti-APRIL antibody molecule is to be administered intravenously or subcutaneously. In one embodiment, the anti-APRIL antibody molecule is to be administered intravenously. In one embodiment, the anti-APRIL antibody molecule is to be administered subcutaneously. In one embodiment, the method further comprises administering the anti-APRIL antibody molecule to the subject.

[0369] Listed implementation plans

[0370] 1. A method for treating a disease, comprising:

[0371] administering an anti-APRIL antibody molecule described herein to a subject in need thereof,

[0372] wherein the antibody molecule is administered at a dose that reduces or may reduce the level of aberrantly glycosylated IgA (ag IgA) in the subject by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%),

[0373] thereby treating the condition.

[0374] 2. A method for treating a disease, comprising:

[0375] administering an anti-APRIL antibody molecule described herein to a subject in need thereof,

[0376] wherein the administration reduces the level of ag IgA in the subject by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0377] thereby treating the condition.

[0378] 3. A method for treating a disease, comprising:

[0379] administering an anti-APRIL antibody molecule described herein to a subject in need thereof,

[0380] wherein the antibody molecule is administered at a dosage (e.g., dose and frequency) that reduces or may reduce the subject's ag IgA levels by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%),

[0381] thereby treating the condition.

[0382] 4. A method of treating a disease, comprising:

[0383] selecting a dose or dosage (e.g., dose and frequency) of an anti-APRIL antibody molecule described herein, wherein administration of the antibody molecule at the dose or dosage reduces or may reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%); and

[0384] administering the antibody molecule to the subject at a selected dose or dosage,

[0385] thereby treating the condition.

[0386] 5. A method for treating a disease, comprising:

[0387] In response to determining that administration of an anti-APRIL antibody molecule described herein reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%), administering the anti-APRIL antibody molecule to the subject,

[0388] thereby treating the condition.

[0389] 6. A method of treating a disease, comprising:

[0390] determining whether administration of an anti-APRIL antibody molecule described herein reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0391] if the antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40%, then administering the antibody molecule is initiated, continued or maintained,

[0392] Optionally wherein if the antibody molecule does not or is unlikely to reduce the level of ag IgA by at least 40%, administration of the antibody molecule is stopped, interrupted or changed, and / or a different therapeutic agent or treatment modality is administered.

[0393] 7. A method of treating a disease, comprising:

[0394] determining whether administration of an anti-APRIL antibody molecule described herein at a dose or dosage reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0395] if the antibody molecule at said dose or dosage reduces or is likely to reduce the level of ag IgA by at least 40%, then initiating, continuing or maintaining administration of the antibody molecule at said dose or dosage,

[0396] Optionally wherein administration of said antibody molecule at said dose or dosage is stopped, interrupted or changed if said antibody molecule at said dose or dosage does not or is unlikely to reduce the level of ag IgA by at least 40%.

[0397] 8. A method of treating a disease, comprising:

[0398] determining whether administration of a therapeutic agent or treatment modality other than an anti-APRIL antibody molecule described herein reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0399] If the therapeutic agent or treatment modality does not or is unlikely to reduce the level of ag IgA by at least 40%, the subject is administered an anti-APRIL antibody molecule described herein.

[0400] 9. A method of reducing the level of ag IgA in a subject, the method comprising:

[0401] For example, administering an anti-APRIL antibody molecule described herein to a subject in need thereof at a dose or dosage that reduces or is likely to reduce the level of ag IgA in the subject by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%),

[0402] Thereby reducing the level of ag IgA.

[0403] 10. A method for selecting an anti-APRIL antibody molecule for treating a condition, the method comprising:

[0404] determining whether administration of an anti-APRIL antibody molecule described herein reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0405] The anti-APRIL antibody molecule is thereby selected.

[0406] 11. A method of selecting a dose or dosage (e.g., dose and frequency) of an anti-APRIL antibody molecule to treat a condition, the method comprising:

[0407] determining whether administration of an anti-APRIL antibody molecule described herein at a dose or dosage reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0408] The dose or dosage is thereby selected.

[0409] 12. A method of selecting a subject for treatment of a condition, the method comprising:

[0410] determining whether administration of an anti-APRIL antibody molecule described herein reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0411] thereby selecting the subject,

[0412] Optionally wherein if the antibody molecule does not or is unlikely to reduce the level of ag IgA by at least 40%, administration of the antibody molecule is stopped, interrupted or changed, or a different therapeutic agent or treatment modality is administered.

[0413] 13. The method of any one of embodiments 1-12, wherein the ag IgA comprises or is ag IgA1.

[0414] 14. The method of any one of embodiments 1-13, wherein the level of ag IgA is reduced by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%) for a predetermined period of time, e.g., at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months.

[0415] 15. The method of any one of embodiments 1-14, wherein the level of a-gIgA is reduced by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%) about 4 weeks after administration of the antibody molecule.

[0416] 16. The method of any one of embodiments 1-15, wherein the level of a-gIgA is reduced by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%) about 8 weeks after administration of the antibody molecule.

[0417] 17. The method of any one of embodiments 1-16, wherein the level of ag IgA is reduced by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%) about 12 weeks after administration of the antibody molecule.

[0418] 18. The method of any one of embodiments 1-17, wherein the level of ag IgA is reduced by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%) about 16 weeks after administration of the antibody molecule.

[0419] 19. The method of any one of embodiments 1-18, wherein the level of ag IgA is reduced by at least 50%.

[0420] 20. The method of any one of embodiments 1-19, wherein the level of ag IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

[0421] 21. The method of any one of embodiments 1-20, wherein the antibody molecule is administered in a single dose.

[0422] 22. The method of any one of embodiments 1-20, wherein the antibody molecule is administered in repeated doses.

[0423] 23. The method of any one of embodiments 1-22, wherein the antibody molecule is administered subcutaneously.

[0424] 24. The method of any one of embodiments 1-22, wherein the antibody molecule is administered intravenously.

[0425] 25. The method of any one of embodiments 1-24, wherein the disorder is an APRIL-associated disorder.

[0426] 26. The method of any one of embodiments 1-25, wherein the condition is associated with abnormal levels of total IgA.

[0427] 27. The method of any one of embodiments 1-26, wherein the disorder is ag IgA-associated disorder.

[0428] 28. The method of any one of embodiments 1-27, wherein the disorder is IgA nephropathy (IgAN).

[0429] 29. The method of embodiment 28, wherein the IgAN is familial IgAN.

[0430] 30. The method of embodiment 28, wherein the IgAN is adult IgAN.

[0431] 31. The method of embodiment 28, wherein the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0432] 32. The method of any one of embodiments 1-27, wherein the condition is chronic kidney disease (CKD) or a condition associated with CKD.

[0433] 33. The method of embodiment 32, wherein the CKD is advanced CKD, eg, estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0434] 34. The method of any one of embodiments 1-27, wherein the condition is Henoch-Schönlein purpura (HSP).

[0435] 35. The method of any one of embodiments 1-27, wherein the condition is cutaneous vasculitis or IgA vasculitis.

[0436] 36. The method of any one of embodiments 1-27, wherein the condition is IgA dermatitis, e.g., IgA bullous dermatosis.

[0437] 37. The method of any one of embodiments 1-27, wherein the disorder is Waldenstrom's macroglobulinemia (WM).

[0438] 38. The method of any one of embodiments 1-27, wherein the disorder is lupus nephritis.

[0439] 39. The method of any one of embodiments 1-38, wherein the subject is human.

[0440] 40. The method of any one of embodiments 1-39, wherein the subject has or is identified as having ag IgA levels that are at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than a reference subject (e.g., a subject not suffering from the disorder, e.g., a healthy or normal subject).

[0441] 41. The method of any one of embodiments 1-40, wherein the subject has or is identified as having a total IgA level that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the total IgA level of a reference subject (e.g., a subject not suffering from the disorder, e.g., a healthy or normal subject).

[0442] 42. The method of any one of embodiments 1-41, wherein the subject has received or is receiving a different therapeutic agent or treatment modality for treating the condition.

[0443] 43. The method of any one of embodiments 1-41, wherein the subject has not received or is not currently receiving a different therapeutic agent or treatment modality for treating the condition.

[0444] 44. The method of any one of embodiments 1-43, wherein the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule.

[0445] 45. The method of any one of embodiments 1-43, wherein the subject is in need of, or is identified as being in need of, receiving a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule.

[0446] 46. ​​The method of embodiment 44 or 45, wherein the subject receives the vaccine before, simultaneously with, or after administration of the antibody molecule.

[0447] 47. The method of any one of embodiments 44-46, wherein administration of the antibody molecule reduces the subject's ability to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%.

[0448] 48. The method of any one of embodiments 44-47, wherein administration of the antibody molecule does not reduce or does not significantly reduce the subject's ability to mount an effective antigen-specific serum IgG and / or IgA response to the vaccine.

[0449] 49. The method of any one of embodiments 44-48, wherein the subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to the vaccine following administration of the antibody molecule.

[0450] 50. The method of any one of embodiments 44-49, wherein the vaccine comprises tetanus toxoid, diphtheria toxoid, or both (e.g., ).

[0451] 51. The method of embodiment 50, wherein the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or more after administration of the antibody molecule.

[0452] 52. The method of any one of embodiments 1-51, wherein the subject has or is identified as having a genomic susceptibility locus for the disorder (e.g., IgA nephropathy).

[0453] 53. The method of any one of embodiments 1-52, further comprising determining whether the subject has a genomic susceptibility locus for the disorder (e.g., IgA nephropathy).

[0454] 54. The method of any one of embodiments 1-53, wherein the antibody molecule comprises antibody 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.

[0455] 55. The method of any one of embodiments 1-54, wherein the antibody molecule comprises antibody 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.

[0456] 56. The method of any one of embodiments 1-55, wherein the level of a-gIgA in a sample from the subject is determined.

[0457] 57. The method of any one of embodiments 1-56, further comprising determining the level of ag IgA in a sample from the subject.

[0458] 58. The method of any one of embodiments 1-57, further comprising determining the level of total IgA in the sample.

[0459] 59. The method of any one of embodiments 1-58, further comprising determining the level of IgM and / or IgG in the sample.

[0460] 60. The method of any one of embodiments 1-59, further comprising obtaining a sample from the subject.

[0461] 61. The method of embodiment 60, wherein the sample is a blood or serum sample.

[0462] 62. The method of any one of embodiments 1-61, further comprising administering a second therapeutic agent or treatment modality to the subject.

[0463] 63. The method of embodiment 62, wherein the second therapeutic agent or treatment modality is a small molecule.

[0464] 64. The method of embodiment 62, wherein the second therapeutic agent or treatment modality is an antibody molecule.

[0465] 65. A method for treating IgA nephropathy, the method comprising:

[0466] administering to a subject in need thereof an effective amount of an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule described herein),

[0467] wherein the subject has received or will receive a vaccine (e.g., a vaccine described herein) within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 weeks of administration of the antibody molecule,

[0468] Thereby treating IgA nephropathy.

[0469] 66. The method of embodiment 65, further comprising administering the vaccine to the subject before, simultaneously with, or after administration of the antibody molecule.

[0470] 67. A method of vaccinating a subject, the method comprising:

[0471] administering to the subject an effective amount of a vaccine (e.g., a vaccine described herein),

[0472] wherein the subject has received or will receive an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule described herein) within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 weeks of administration of the vaccine,

[0473] The subject is thereby vaccinated.

[0474] 68. The method of embodiment 67, further comprising administering the antibody molecule to the subject before, simultaneously with, or after administration of the vaccine.

[0475] 69. The method of any one of embodiments 44-68, wherein the vaccine is administered intramuscularly.

[0476] 70. A composition for treating IgA nephropathy in a subject, wherein the composition comprises an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule described herein) at a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg,

[0477] wherein the subject has received or will receive a vaccine (e.g., a vaccine described herein) within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 weeks of administration of the antibody molecule.

[0478] 71. The composition for use according to embodiment 70, wherein the subject has been administered the vaccine before, simultaneously with or after administration of the antibody molecule.

[0479] 72. A composition for vaccinating a subject, the composition comprising an effective amount of a vaccine (e.g., a vaccine described herein),

[0480] wherein the subject has received or will receive an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule described herein) within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 weeks of administration of the vaccine, wherein the subject has received or will receive the anti-APRIL antibody molecule at a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg or 800 mg.

[0481] 73. The composition for use as described in embodiment 72, wherein the antibody molecule is administered to the subject before, simultaneously with or after administration of the vaccine.

[0482] 74. A composition for treating a condition in a subject, the composition comprising:

[0483] a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg of an anti-APRIL antibody molecule described herein; and

[0484] wherein the dosage reduces or is likely to reduce the level of aberrantly glycosylated IgA (ag IgA) in the subject by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%).

[0485] 75. A composition for treating a disorder in a subject, the composition comprising a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg of an anti-APRIL antibody molecule described herein,

[0486] wherein the dosage reduces the subject's ag IgA level by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%).

[0487] 76. A composition for treating a disorder in a subject, the composition comprising an anti-APRIL antibody molecule described herein at a dosage (e.g., dose and frequency) that reduces or may reduce the level of ag IgA in the subject by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%).

[0488] wherein the dosage is about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or at a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg.

[0489] 77. A composition for treating a disorder in a subject, said composition comprising an anti-APRIL antibody molecule described herein administered to said subject at a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg;

[0490] wherein the composition is formulated to be administered if administration of a therapeutic agent or treatment other than an anti-APRIL antibody molecule described herein reduces or is likely to reduce the level of ag IgA in the subject by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%).

[0491] 78. A composition for reducing the level of ag IgA in a subject, the composition comprising a dose or dosage of an anti-APRIL antibody molecule described herein to the subject that reduces or may reduce the level of ag IgA in the subject by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%).

[0492] wherein the dose or dosage is about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg or 800 mg.

[0493] 79. A method for treating IgA nephropathy, the method comprising:

[0494] administering to a subject in need thereof an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule described herein) at a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg,

[0495] wherein the subject has received or will receive a vaccine (e.g., a vaccine described herein) within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 weeks of administration of the antibody molecule,

[0496] Thereby treating IgA nephropathy.

[0497] 80. The method of embodiment 79, further comprising administering the vaccine to the subject before, simultaneously with, or after administration of the antibody molecule.

[0498] 81. A method of vaccinating a subject, the method comprising:

[0499] administering to the subject an effective amount of a vaccine (e.g., a vaccine described herein),

[0500] wherein the subject has received or will receive an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule described herein) within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 weeks of administration of the vaccine, wherein the subject has received or will receive the anti-APRIL antibody molecule at a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg;

[0501] The subject is thereby vaccinated.

[0502] 82. The method of embodiment 81, further comprising administering the antibody molecule to the subject before, simultaneously with, or after administering the vaccine.

[0503] 83. A method of treating a condition, the method comprising:

[0504] administering an anti-APRIL antibody molecule described herein to a subject in need thereof,

[0505] wherein the antibody molecule is administered at a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg; and

[0506] wherein the dosage administered to the subject reduces or is likely to reduce the level of aberrantly glycosylated IgA (ag IgA) in the subject by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0507] thereby treating the condition.

[0508] 84. A method of treating a condition, the method comprising:

[0509] administering to a subject in need thereof an anti-APRIL antibody molecule described herein at a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg,

[0510] wherein the administration reduces the level of ag IgA in the subject by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0511] thereby treating the condition.

[0512] 85. A method of treating a condition, the method comprising:

[0513] administering an anti-APRIL antibody molecule described herein to a subject in need thereof,

[0514] wherein the antibody molecule is administered at a dosage (e.g., dose and frequency) that reduces or may reduce the subject's ag IgA levels by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%), and

[0515] wherein the dosage is about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg;

[0516] thereby treating the condition.

[0517] 86. A method of treating a condition, the method comprising:

[0518] selecting a dose or dosage (e.g., dose and frequency) of an anti-APRIL antibody molecule described herein,

[0519] wherein the dose or dosage is about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg; and

[0520] wherein administration of the antibody molecule at the dose or dosage reduces or may reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%); and

[0521] administering the antibody molecule to the subject at a selected dose or dosage,

[0522] thereby treating the condition.

[0523] 87. A method of treating a condition, the method comprising:

[0524] In response to determining that administration of an anti-APRIL antibody molecule described herein reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%), administering the anti-APRIL antibody molecule to the subject at a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg,

[0525] thereby treating the condition.

[0526] 88. A method of treating a condition, the method comprising:

[0527] determining whether administration of an anti-APRIL antibody molecule described herein reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0528] If the antibody molecule reduces or may reduce the level of ag IgA by at least 40%, administration of the antibody molecule is initiated, continued or maintained at a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg or 800 mg,

[0529] Optionally wherein if the antibody molecule does not or is unlikely to reduce the level of ag IgA by at least 40%, administration of the antibody molecule is stopped, interrupted or changed, and / or a different therapeutic agent or treatment modality is administered.

[0530] 89. A method of treating a condition, the method comprising:

[0531] determining whether administration of an anti-APRIL antibody molecule described herein at a dose or dosage reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0532] if the antibody molecule at said dose or dosage reduces or is likely to reduce the level of ag IgA by at least 40%, then initiating, continuing or maintaining administration of the antibody molecule at said dose or dosage,

[0533] wherein the dose or dosage is about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or at a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg;

[0534] Optionally wherein administration of said antibody molecule at said dose or dosage is stopped, interrupted or changed if said antibody molecule at said dose or dosage does not or is unlikely to reduce the level of ag IgA by at least 40%.

[0535] 90. A method of treating a condition, the method comprising:

[0536] determining whether administration of a therapeutic agent or treatment modality other than an anti-APRIL antibody molecule described herein reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0537] If the therapeutic agent or treatment modality does not or is unlikely to reduce the level of ag IgA by at least 40%, the subject is administered an anti-APRIL antibody molecule described herein at a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg.

[0538] 91. A method of reducing the level of ag IgA in a subject, the method comprising:

[0539] administering to a subject in need thereof an anti-APRIL antibody molecule described herein at a dose or dosage that reduces or is likely to reduce the level of ag IgA in the subject by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%),

[0540] wherein the dose or dosage is about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or at a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg;

[0541] Thereby reducing the level of ag IgA.

[0542] 92. A method of selecting an anti-APRIL antibody molecule for treating a disorder, the method comprising:

[0543] determining whether administration of an anti-APRIL antibody molecule described herein at a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0544] The anti-APRIL antibody molecule is thereby selected.

[0545] 93. A method of selecting a dose or dosage (e.g., dose and frequency) of an anti-APRIL antibody molecule to treat a condition, the method comprising:

[0546] determining whether administration of an anti-APRIL antibody molecule described herein at a dose or dosage reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0547] wherein the dose or dosage is about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or at a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg;

[0548] The dose or dosage is thereby selected.

[0549] 94. A method of selecting a subject for treatment of a condition, the method comprising:

[0550] determining whether administration of an anti-APRIL antibody molecule described herein at a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%),

[0551] thereby selecting the subject,

[0552] Optionally wherein if the antibody molecule does not or is unlikely to reduce the level of ag IgA by at least 40%, administration of the antibody molecule is stopped, interrupted or changed, or a different therapeutic agent or treatment modality is administered.

[0553] 95. The method of any one of embodiments 79-94, wherein the ag IgA comprises or is ag IgA1.

[0554] 96. The method of any one of embodiments 79-95, wherein the level of ag IgA is reduced by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%) for a predetermined period of time, e.g., at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months.

[0555] 97. The method of any one of embodiments 79-96, wherein the level of ag IgA is reduced by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%) about 4 weeks after administration of the antibody molecule.

[0556] 98. The method of any one of embodiments 79-97, wherein the level of ag IgA is reduced by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%) about 8 weeks after administration of the antibody molecule.

[0557] 99. The method of any one of embodiments 79-98, wherein the level of ag IgA is reduced by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%) about 12 weeks after administration of the antibody molecule.

[0558] 100. The method of any one of embodiments 79-99, wherein the level of ag IgA is reduced by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%) about 16 weeks after administration of the antibody molecule.

[0559] 101. The method of any one of embodiments 79-100, wherein the level of ag IgA is reduced by at least 50%.

[0560] 102. The method of any one of embodiments 79-101, wherein the level of ag IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

[0561] 103. The method of any one of embodiments 79-102, wherein the antibody molecule is administered in a single dose, e.g., over a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 months.

[0562] 104. The method of any one of embodiments 79-102, wherein the antibody molecule is administered in repeated doses.

[0563] 105. The method of any one of embodiments 79-104, wherein the antibody molecule is administered subcutaneously.

[0564] 106. The method of any one of embodiments 79-104, wherein the antibody molecule is administered intravenously.

[0565] 107. The method of any one of embodiments 79-106, wherein the disorder is an APRIL-associated disorder.

[0566] 108. The method of any one of embodiments 79-107, wherein the condition is associated with abnormal levels of total IgA.

[0567] 109. The method of any one of embodiments 79-108, wherein the disorder is ag IgA-associated disorder.

[0568] 110. The method of any one of embodiments 79-109, wherein the disorder is IgA nephropathy (IgAN).

[0569] 111. The method of embodiment 110, wherein the IgAN is familial IgAN.

[0570] 112. The method of embodiment 110, wherein the IgAN is adult IgAN.

[0571] 113. The method of embodiment 110, wherein the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0572] 114. The method of any one of embodiments 79-108, wherein the disorder is chronic kidney disease (CKD) or a disorder associated with CKD.

[0573] 115. The method of embodiment 114, wherein the CKD is advanced CKD, eg, estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0574] 116. The method of any one of embodiments 79-108, wherein the condition is Henoch-Schönlein purpura (HSP).

[0575] 117. The method of any one of embodiments 79-108, wherein the condition is cutaneous vasculitis or IgA vasculitis.

[0576] 118. The method of any one of embodiments 79-108, wherein the condition is IgA dermatitis, e.g., IgA bullous dermatosis.

[0577] 119. The method of any one of embodiments 79-108, wherein the disorder is Waldenstrom's macroglobulinemia (WM).

[0578] 120. The method of any one of embodiments 79-108, wherein the condition is lupus nephritis.

[0579] 121. The method of any one of embodiments 79-120, wherein the subject is human.

[0580] 122. The method of any one of embodiments 79-121, wherein the subject has or is identified as having ag IgA levels that are at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than a reference subject (e.g., a subject not suffering from the disorder, e.g., a healthy or normal subject).

[0581] 123. The method of any one of embodiments 79-122, wherein the subject has or is identified as having a total IgA level that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the total IgA level of a reference subject (e.g., a subject not suffering from the disorder, e.g., a healthy or normal subject).

[0582] 124. The method of any one of embodiments 79-123, wherein the subject has received or is receiving a different therapeutic agent or treatment modality for treating the condition.

[0583] 125. The method of any one of embodiments 79-123, wherein the subject has not received or is not currently receiving a different therapeutic agent or treatment modality for treating the condition.

[0584] 126. The method of any one of embodiments 79-125, wherein the subject has received, is receiving, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule.

[0585] 127. The method of any one of embodiments 79-125, wherein the subject is in need of or identified as in need of receiving a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule.

[0586] 128. The method of embodiment 126 or 127, wherein the subject receives the vaccine before, simultaneously with, or after administration of the antibody molecule.

[0587] 129. The method of any one of embodiments 126-128, wherein administration of the antibody molecule reduces the subject's ability to mount an effective antigen-specific serum IgG and / or IgA response to a vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%.

[0588] 130. The method of any one of embodiments 126-129, wherein administration of the antibody molecule does not reduce or does not significantly reduce the subject's ability to mount an effective antigen-specific serum IgG and / or IgA response to the vaccine.

[0589] 131. The method of any one of embodiments 126-130, wherein the subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to the vaccine following administration of the antibody molecule.

[0590] 132. The method of any one of embodiments 126-131, wherein the vaccine comprises tetanus toxoid, diphtheria toxoid, or both (e.g., ).

[0591] 133. The method of embodiment 132, wherein the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or more after administration of the antibody molecule.

[0592] 134. The method of any one of embodiments 79-133, wherein the subject has or is identified as having a genomic susceptibility locus for the disorder (e.g., IgA nephropathy).

[0593] 135. The method of any one of embodiments 79-134, further comprising determining whether the subject has a genomic susceptibility locus for the disorder (e.g., IgA nephropathy).

[0594] 136. The method of any one of embodiments 79-135, wherein the antibody molecule comprises antibody 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 2419-1305, 2419-130 6. the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 of any one of 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.

[0595] 137. The method of any one of embodiments 79-136, wherein the antibody molecule comprises antibody 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 241 9-1305, 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.

[0596] 138. The method of any one of embodiments 79-137, wherein the level of ag IgA in a sample from the subject is determined.

[0597] 139. The method of any one of embodiments 79-138, further comprising determining the level of ag IgA in a sample from the subject.

[0598] 140. The method of any one of embodiments 79-139, further comprising determining the level of total IgA in the sample.

[0599] 141. The method of any one of embodiments 79-140, further comprising determining the level of IgM and / or IgG in the sample.

[0600] 142. The method of any one of embodiments 79-141, further comprising obtaining a sample from the subject.

[0601] 143. The method of embodiment 142, wherein the sample is a blood or serum sample.

[0602] 144. The method of any one of embodiments 79-143, further comprising administering a second therapeutic agent or treatment modality to the subject.

[0603] 145. The method of embodiment 144, wherein the second therapeutic agent or treatment modality is a small molecule.

[0604] 146. The method of embodiment 144, wherein the second therapeutic agent or treatment modality is an antibody molecule.

[0605] 147. A method or composition for use as described in any one of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered to the subject at a concentration of about 100, 150, 175, 180, 190, 200, 210, 220, 225, 230, 240, 250 or 300 mg / mL.

[0606] 148. A method or composition for use as described in any one of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered to the subject at a concentration of about 200 mg / mL.

[0607] 149. A method or composition for use as described in any one of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered to the subject at a fixed dose of about 200, 250, 300, 450, 400, 450, 500, 550, 600, 650, 700, 750 or 800 mg.

[0608] 150. A method or composition for use as described in any one of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered to the subject at a fixed dose of about 200 mg (eg, in a volume of about 1 mL).

[0609] 151. A method or composition for use as described in any of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered to the subject at a fixed dose of about 400 mg (e.g., in a total volume of about 2 mL, e.g., two administrations of 1 mL volume or one administration of 2 mL volume).

[0610] 152. A method or composition for use as described in any one of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered to the subject at a fixed dose of at least 200 mg.

[0611] 153. A method or composition for use as described in any one of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered to the subject at a fixed dose of 800 mg or less.

[0612] 154. A method or composition for use as described in any of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered to the subject at a fixed dose of about 600 mg (e.g., in a total volume of about 3 mL, e.g., one administration in a 2 mL volume and one administration in a 1 mL volume).

[0613] 155. The method or composition for use as described in any one of the preceding embodiments, wherein a single dose of the anti-APRIL antibody molecule is administered to the subject.

[0614] 156. A method or composition for use as described in any of the preceding embodiments, wherein one or more additional doses of the anti-APRIL antibody molecule are administered to the subject (e.g., 24 hours, 48 ​​hours, 72 hours, 4 days, 5 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months or 6 months after the first administration).

[0615] 157. A method or composition for use as described in any one of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered subcutaneously to the subject.

[0616] 158. A method or composition for use as described in any one of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered intravenously to the subject.

[0617] 159. A method or composition for use as described in any one of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered in liquid form.

[0618] 160. An anti-APRIL antibody molecule, or a pharmaceutical composition comprising the anti-APRIL antibody molecule, for use in a method of treating a disorder in a human subject.

[0619] wherein the antibody molecule is administered at a dose of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg;

[0620] wherein the administration reduces the level of aberrantly glycosylated IgA (ag IgA) in the subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%; and

[0621] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0622] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0623] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0624] Optionally wherein the disorder is IgA nephropathy.

[0625] 161. An anti-APRIL antibody molecule, or a pharmaceutical composition comprising the anti-APRIL antibody molecule, for use in a method of reducing the level of ag IgA in a human subject.

[0626] wherein the antibody molecule is administered at a dose of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg;

[0627] wherein the administration reduces the subject's level of ag IgA by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%; and

[0628] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0629] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0630] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0631] Optionally wherein the subject has, or is at risk of having, a disorder, eg, IgA nephropathy.

[0632] 162. An anti-APRIL antibody molecule, or a pharmaceutical composition comprising the anti-APRIL antibody molecule, for use in a method of treating a disorder in a human subject.

[0633] The method comprises selecting a dose or dosage of the antibody molecule;

[0634] wherein administration of the selected dose or dosage of the antibody molecule reduces or is likely to reduce the level of ag IgA in the subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%; and

[0635] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0636] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0637] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0638] Optionally wherein the antibody molecule is administered at a dose of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg or 800 mg,

[0639] Optionally wherein the disorder is IgA nephropathy.

[0640] 163. An anti-APRIL antibody molecule, or a pharmaceutical composition comprising the anti-APRIL antibody molecule, for use in a method of treating a disorder in a human subject.

[0641] wherein the method comprises administering the antibody molecule to the subject at a dose of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg, in response to determining that administration of the antibody molecule reduces or is likely to reduce the level of ag IgA in the subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%; and

[0642] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0643] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0644] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0645] Optionally wherein the disorder is IgA nephropathy.

[0646] 164. An anti-APRIL antibody molecule, or a pharmaceutical composition comprising the anti-APRIL antibody molecule, for use in a method of treating a disorder in a human subject.

[0647] wherein the method comprises determining whether administration of the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA in the subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%,

[0648] if the antibody molecule reduces or may reduce the level of ag IgA by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%, initiating, continuing or maintaining administration of the antibody molecule at a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg or 800 mg; and

[0649] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0650] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0651] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0652] Optionally wherein the antibody molecule is administered at a dose of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg or 800 mg,

[0653] Optionally wherein the disorder is IgA nephropathy,

[0654] Optionally wherein if the antibody molecule does not or is unlikely to reduce the levels of ag IgA by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%, administration of the antibody molecule is stopped, interrupted or changed, and / or a different therapeutic agent or treatment modality is administered.

[0655] 165. An anti-APRIL antibody molecule, or a pharmaceutical composition comprising the anti-APRIL antibody molecule, for use in a method of treating a disorder in a human subject.

[0656] wherein the method comprises determining whether administration of a therapeutic agent or treatment other than the antibody molecule reduces or is likely to reduce the level of ag IgA in a subject in need thereof by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%,

[0657] if the therapeutic agent or treatment modality does not or is unlikely to reduce the level of ag IgA by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%, administering the antibody molecule to the subject at a dose of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg or 800 mg; and

[0658] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0659] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0660] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0661] Optionally wherein the disorder is IgA nephropathy.

[0662] 166. An anti-APRIL antibody molecule, or a pharmaceutical composition comprising the anti-APRIL antibody molecule, for use in a method of treating a disorder in a human subject.

[0663] wherein the antibody molecule is administered at a dose of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg; and

[0664] wherein the subject has received or will receive a vaccine within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 weeks of administration of the antibody molecule, optionally wherein the vaccine comprises tetanus toxoid, diphtheria toxoid or both (e.g., ),

[0665] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0666] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0667] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0668] Optionally wherein the disorder is IgA nephropathy,

[0669] Optionally, administration of the selected dose or dosage of the antibody molecule reduces or may reduce the level of ag IgA in the subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%.

[0670] 167. A method of treating a condition, the method comprising:

[0671] administering the anti-APRIL antibody molecule to a human subject in need thereof at a dose of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a flat dose of about 200 mg, 400 mg, 600 mg, or 800 mg;

[0672] wherein the administration reduces the level of aberrantly glycosylated IgA (ag IgA) in the subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%; and

[0673] The antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3).

[0674] Optionally, the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0675] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0676] Optionally wherein the disorder is IgA nephropathy,

[0677] thereby treating the condition.

[0678] 168. A method of reducing the level of ag IgA, the method comprising:

[0679] administering an anti-APRIL antibody molecule to a human subject in need thereof,

[0680] wherein the antibody molecule is administered at a dose of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg;

[0681] wherein the administration reduces the subject's level of ag IgA by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%; and

[0682] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0683] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0684] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0685] Optionally wherein the subject has, or is at risk of having, a disorder, such as IgA nephropathy,

[0686] Thereby reducing the level of ag IgA.

[0687] 169. A method of treating a condition, the method comprising:

[0688] selecting a dose or dosage of an anti-APRIL antibody molecule;

[0689] wherein administration of the selected dose or dosage of the antibody molecule reduces or is likely to reduce the level of ag IgA in the subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%; and

[0690] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0691] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0692] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0693] Optionally wherein the antibody molecule is administered at a dose of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg or 800 mg,

[0694] Optionally wherein the subject has, or is at risk of developing, IgA nephropathy,

[0695] thereby treating the condition.

[0696] 170. A method of treating a condition, the method comprising:

[0697] administering the anti-APRIL antibody molecule to a human subject in need thereof at a dose of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg in response to determining that said administration of said antibody molecule reduces or is likely to reduce the level of ag IgA in said subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%; and

[0698] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0699] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0700] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0701] Optionally wherein the disorder is IgA nephropathy,

[0702] thereby treating the condition.

[0703] 171. A method of treating a condition, the method comprising:

[0704] determining whether administration of the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA in the subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%,

[0705] if the antibody molecule reduces or may reduce the level of ag IgA by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%, initiating, continuing or maintaining administration of the antibody molecule at a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg or 800 mg; and

[0706] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0707] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0708] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0709] Optionally wherein the antibody molecule is administered at a dose of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg or 800 mg,

[0710] Optionally wherein if the antibody molecule does not or is unlikely to reduce the levels of ag IgA by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%, administration of the antibody molecule is stopped, interrupted or changed, and / or a different therapeutic agent or treatment modality is administered,

[0711] Optionally wherein the disorder is IgA nephropathy,

[0712] thereby treating the condition.

[0713] 172. A method of treating a condition, the method comprising:

[0714] determining whether administration of a therapeutic agent or treatment modality other than an anti-APRIL antibody molecule reduces or is likely to reduce the level of a-gIgA in a subject in need thereof by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%,

[0715] if the therapeutic agent or treatment modality does not or is unlikely to reduce the level of ag IgA by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%, administering the antibody molecule to the human subject at a dose of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg or 800 mg; and

[0716] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0717] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0718] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0719] Optionally wherein the disorder is IgA nephropathy,

[0720] thereby treating the condition.

[0721] 173. A method of treating a condition, the method comprising:

[0722] administering the anti-APRIL antibody molecule to a human subject in need thereof at a dose of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg; and

[0723] wherein the subject has received or will receive a vaccine within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 weeks of administration of the antibody molecule, optionally wherein the vaccine comprises tetanus toxoid, diphtheria toxoid or both (e.g., ),

[0724] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0725] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0726] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0727] Optionally wherein the disorder is IgA nephropathy,

[0728] Optionally wherein administration of the selected dose or dosage of the antibody molecule reduces or is likely to reduce the level of ag IgA in the subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%,

[0729] thereby treating the condition.

[0730] 174. A method of selecting an anti-APRIL antibody molecule for treating a disorder, the method comprising:

[0731] determining whether administration of a dose or dosage of the antibody molecule reduces or is likely to reduce the level of ag IgA in a human subject in need thereof by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%,

[0732] wherein the dosage is about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or at a fixed dose of about 200 mg, 400 mg, 600 mg or 800 mg,

[0733] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0734] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0735] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0736] Optionally wherein the disorder is IgA nephropathy,

[0737] The antibody molecule is thereby selected.

[0738] 175. A method of selecting a dose or dosage of an anti-APRIL antibody molecule to treat a condition, the method comprising:

[0739] determining whether administration of a dose or dosage of the antibody molecule reduces or is likely to reduce the level of ag IgA in a human subject in need thereof by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%,

[0740] Optionally wherein the dose is about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or at a fixed dose of about 200 mg, 400 mg, 600 mg or 800 mg,

[0741] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0742] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0743] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0744] Optionally wherein the disorder is IgA nephropathy,

[0745] The dose or dosage is thereby selected.

[0746] 176. A method of selecting a human subject for treatment of a condition, the method comprising:

[0747] determining whether administration of a dosage of about 0.5 mg / kg, 2.0 mg / kg, 6 mg / kg, 9 mg / kg, 9.1 mg / kg, 12 mg / kg, or a fixed dose of about 200 mg, 400 mg, 600 mg or 800 mg of the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA in the subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%,

[0748] Optionally, the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0749] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0750] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16,

[0751] Optionally wherein the disorder is IgA nephropathy,

[0752] thereby selecting the subject,

[0753] 177. The antibody molecule, pharmaceutical composition, or method for use as described in any one of embodiments 160-176, wherein the ag IgA comprises or is ag IgAl.

[0754] 178. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-177, wherein the level of a-gIgA is reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% for a predetermined period of time, for example, at least 1, 2, 3 or 4 weeks, or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months.

[0755] 179. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-178, wherein the level of ag IgA is reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% about 4 weeks after administration of the antibody molecule.

[0756] 180. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-179, wherein the level of ag IgA is reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% about 8 weeks after administration of the antibody molecule.

[0757] 181. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-180, wherein the level of ag IgA is reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% about 12 weeks after administration of the antibody molecule.

[0758] 182. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-181, wherein the level of ag IgA is reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% about 16 weeks after administration of the antibody molecule.

[0759] 183. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-182, wherein the level of ag IgA is reduced by at least 50%.

[0760] 184. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-183, wherein the level of a-gIgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%.

[0761] 185. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-184, e.g., over a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18 months.

[0762] 186. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-185, wherein the antibody molecule is administered in repeated doses, e.g., over a period of at least 3, 6, 9, 12, 15, 18, 24, 30 or 36 months, optionally wherein the subject is administered one or more additional doses of the anti-APRIL antibody molecule (e.g., 24 hours, 48 ​​hours, 72 hours, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months or 6 months after the first administration).

[0763] 187. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-186, wherein the antibody molecule is administered subcutaneously.

[0764] 188. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-186, wherein the antibody molecule is administered intravenously.

[0765] 189. The antibody molecule for use, the pharmaceutical composition, the method according to any one of embodiments 160-188, wherein the disorder is an APRIL-associated disorder.

[0766] 190. The antibody molecule, pharmaceutical composition, method for use according to any one of embodiments 160-189, wherein the disorder is associated with abnormal levels of total IgA.

[0767] 191. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-190, wherein the disorder is ag IgA-associated disorder.

[0768] 192. The antibody molecule for use, the pharmaceutical composition, the method as described in any one of embodiments 160-191, wherein the disorder is IgA nephropathy (IgAN).

[0769] 193. The antibody molecule, pharmaceutical composition, method for use as described in embodiment 192, wherein the IgAN is familial IgAN.

[0770] 194. The antibody molecule, pharmaceutical composition, method for use as described in embodiment 192, wherein the IgAN is adult IgAN.

[0771] 195. The antibody molecule, pharmaceutical composition, or method for use as described in embodiment 192, wherein the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0772] 196. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-191, wherein the disorder is chronic kidney disease (CKD) or a disorder associated with CKD.

[0773] 197. The antibody molecule, pharmaceutical composition, method for use as described in embodiment 196, wherein the CKD is advanced CKD, e.g., estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0774] 198. The antibody molecule for use, the pharmaceutical composition, the method as described in any one of embodiments 160-191, wherein the disorder is Henoch-Schonlein purpura (HSP).

[0775] 199. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-191, wherein the disorder is cutaneous vasculitis or IgA vasculitis.

[0776] 200. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-191, wherein the disorder is IgA dermatitis, eg, IgA bullous dermatosis.

[0777] 201. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-191, wherein the disorder is Waldenstrom's macroglobulinemia (WM).

[0778] 202. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-191, wherein the disorder is lupus nephritis.

[0779] 203. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-202, wherein the subject is a human patient.

[0780] 204. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-203, wherein the subject has or is identified as having ag IgA levels that are at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the levels of a reference subject (e.g., a subject not suffering from the disorder, e.g., a healthy or normal subject).

[0781] 205. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-204, wherein the subject has or is identified as having a total IgA level that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5 or 5 times higher than the total IgA level of a reference subject (e.g., a subject not suffering from the disorder, e.g., a healthy or normal subject).

[0782] 206. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-205, wherein the subject has received or is receiving a different therapeutic agent or treatment modality for treating the condition.

[0783] 207. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-206, wherein the subject has not received or is not currently receiving a different therapeutic agent or treatment modality for treating the condition.

[0784] 208. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-207, wherein the subject has received, is receiving, or will receive a vaccine, for example, within 1, 2, 3, 4, 5, or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule.

[0785] 209. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-208, wherein the subject is in need or is determined to be in need of receiving a vaccine, for example, within 1, 2, 3, 4, 5 or 6 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 weeks of administration of the antibody molecule.

[0786] 210. The antibody molecule, pharmaceutical composition, method for use according to embodiment 208 or 209, wherein the subject receives the vaccine before, simultaneously with or after administration of the antibody molecule.

[0787] 211. The antibody molecule, pharmaceutical composition, or method for use as described in any one of embodiments 160-210, wherein administration of the antibody molecule reduces the subject's ability to mount an effective antigen-specific serum IgG and / or IgA response to the vaccine by no more than 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%.

[0788] 212. The antibody molecule, pharmaceutical composition, or method for use as described in any one of embodiments 160-211, wherein administration of the antibody molecule does not reduce or does not significantly reduce the subject's ability to produce an effective antigen-specific serum IgG and / or IgA response to the vaccine.

[0789] 213. The antibody molecule, pharmaceutical composition, or method for use as described in any one of embodiments 160-212, wherein the subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to the vaccine after administration of the antibody molecule.

[0790] 214. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-213, wherein the vaccine comprises tetanus toxoid, diphtheria toxoid, or both (e.g., ).

[0791] 215. The antibody molecule, pharmaceutical composition, or method for use as described in embodiment 214, wherein the subject has or maintains effective (e.g., protective) tetanus and / or diphtheria anti-toxoid IgG levels (e.g., equal to or greater than 0.1 IU / mL in the blood), e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or more after administration of the antibody molecule.

[0792] 216. The antibody molecule, pharmaceutical composition, or method for use as described in any one of embodiments 160-215, wherein the subject has or is identified as having a genomic susceptibility locus for the disorder (e.g., IgA nephropathy).

[0793] 217. The antibody molecule, pharmaceutical composition, or method for use as described in any one of embodiments 160-216, further comprising determining whether the subject has a genomic susceptibility locus for the disorder (e.g., IgA nephropathy).

[0794] 218. The antibody molecule, pharmaceutical composition, or method for use according to any one of embodiments 160 to 217, wherein the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0795] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0796] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0797] 219. The antibody molecule, pharmaceutical composition, or method for use according to any one of embodiments 160 to 218, wherein the antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO: 286,

[0798] Optionally wherein the antibody molecule is IgG2.

[0799] 220. The antibody molecule, pharmaceutical composition, method for use according to any one of embodiments 160-219, wherein the level of ag IgA in a sample from said subject is determined.

[0800] 221. The antibody molecule, pharmaceutical composition, or method for use as described in any one of embodiments 160-220, further comprising determining the level of a-gIgA in a sample from the subject.

[0801] 222. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-221, further comprising determining the level of total IgA in the sample.

[0802] 223. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-222, further comprising determining the level of total IgM and / or IgG in said sample.

[0803] 224. The antibody molecule, pharmaceutical composition, or method for use as described in any one of embodiments 160-223, further comprising obtaining a sample from the subject.

[0804] 225. The antibody molecule, pharmaceutical composition, or method for use as described in embodiment 224, wherein the sample is a blood or serum sample.

[0805] 226. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-225, further comprising administering a second therapeutic agent or treatment modality to the subject.

[0806] 227. The antibody molecule, pharmaceutical composition, or method for use as described in embodiment 226, wherein the second therapeutic agent or treatment modality is a small molecule.

[0807] 228. The antibody molecule, pharmaceutical composition, or method for use as described in embodiment 227, wherein the second therapeutic agent or treatment modality is an antibody molecule.

[0808] 229. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-228, wherein the anti-APRIL antibody molecule is administered to the subject at a concentration of about 100, 150, 175, 180, 190, 200, 210, 220, 225, 230, 240, 250 or 300 mg / mL.

[0809] 230. The antibody molecule, pharmaceutical composition, method for use according to any one of embodiments 160-229, wherein the anti-APRIL antibody molecule is administered to the subject at a concentration of about 200 mg / mL.

[0810] 231. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-230, wherein the anti-APRIL antibody molecule is administered to the subject at a fixed dose of about 200, 250, 300, 450, 400, 450, 500, 550, 600, 650, 700, 750 or 800 mg.

[0811] 232. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-231, wherein the anti-APRIL antibody molecule is administered to the subject at a fixed dose of about 200 mg (e.g., in a volume of about 1 mL).

[0812] 233. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-232, wherein the anti-APRIL antibody molecule is administered to the subject at a fixed dose of about 400 mg (e.g., in a total volume of about 2 mL, e.g., two administrations of 1 mL volume or one administration of 2 mL volume).

[0813] 234. The antibody molecule, pharmaceutical composition, method for use as described in any one of embodiments 160-233, wherein the anti-APRIL antibody molecule is administered to the subject at a fixed dose of about 600 mg (e.g., in a total volume of about 3 mL, e.g., one administration in a 2 mL volume and one administration in a 1 mL volume).

[0814] 235. The antibody molecule, the pharmaceutical composition for use or the method according to any one of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered to the subject at a fixed dose of at least 200 mg.

[0815] 236. The antibody molecule, the pharmaceutical composition for use or the method according to any one of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered to the subject at a fixed dose of 800 mg or less.

[0816] 237. The antibody molecule, the pharmaceutical composition for use or the method according to any one of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered in the form of a liquid composition.

[0817] 238. A method of improving renal function, comprising administering an anti-APRIL antibody molecule to a subject in need thereof,

[0818] Thereby improving kidney function.

[0819] 239. The method of embodiment 238, wherein the method reverses or arrests progression of decreased renal function in the subject.

[0820] 240. The method of any one of embodiments 238-239, wherein the improved renal function comprises regeneration of the subject's kidneys.

[0821] 241. The method of any one of embodiments 238-240, wherein the improved renal function comprises an increase in estimated glomerular filtration rate (eGFR) of the subject's kidneys.

[0822] 242. The method of any one of embodiments 238-241, wherein the improved renal function comprises a reduction in proteinuria in the subject's kidneys.

[0823] 243. The method of any one of embodiments 238-242, wherein the method improves renal function in the subject within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months after administration of the antibody molecule (e.g., after the first, second, or third administration).

[0824] 244. The method of any one of embodiments 238-243, wherein the method improves renal function in the subject after 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 administrations of the antibody molecule.

[0825] 245. The method of any one of embodiments 238-244, wherein the method improves renal function for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months.

[0826] 246. A method of preserving (e.g., maintaining or increasing) estimated glomerular filtration rate (eGFR) of a kidney, the method comprising administering to a subject in need thereof an anti-APRIL antibody molecule comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of antibody 2419-1406 or VH and VL of antibody 2419-1406,

[0827] The renal eGFR is thereby preserved (eg, maintained or increased).

[0828] 247. A method of reducing proteinuria in the kidney, the method comprising administering an anti-APRIL antibody molecule to a subject in need thereof,

[0829] This reduces proteinuria.

[0830] 248. The method of embodiment 247, wherein the reduction in proteinuria is determined by measuring urine protein / creatinine ratio (uPCR), e.g., as described in Example 8.

[0831] 249. The method of any one of embodiments 247-248, wherein the method reduces proteinuria in the subject within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months after administration of the antibody molecule (e.g., after the first, second, or third administration).

[0832] 250. The method of embodiment 249, wherein the method reduces proteinuria in the subject within about 3 months after administration.

[0833] 251. The method of embodiment 249, wherein the method reduces proteinuria in the subject within about 6 months after administration.

[0834] 252. The method of embodiment 249, wherein the method reduces proteinuria in the subject within about 1 year after administration.

[0835] 253. The method of embodiment 249, wherein the method reduces proteinuria in the subject within about 2 years after administration.

[0836] 254. The method of embodiment 249, wherein the method reduces proteinuria in the subject within about 3 years after administration.

[0837] 255. The method of embodiment 249, wherein the method reduces proteinuria in the subject within about 4 years after administration.

[0838] 256. The method of any one of embodiments 247-255, wherein the method reduces proteinuria in the subject after 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 administrations of the antibody molecule.

[0839] 257. The method of any one of embodiments 247-256, wherein the method reduces proteinuria for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months.

[0840] 258. A method of inducing renal recovery, the method comprising administering an anti-APRIL antibody molecule to a subject in need thereof,

[0841] Thereby inducing kidney recovery.

[0842] 259. A method of inducing kidney regeneration, the method comprising administering an anti-APRIL antibody molecule to a subject in need thereof,

[0843] This induces kidney regeneration.

[0844] 260. A method of reducing an autoantibody response, the method comprising administering an anti-APRIL antibody molecule to a subject in need thereof,

[0845] This reduces autoantibody response.

[0846] 261. The method of any one of the preceding embodiments, wherein the antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),

[0847] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or

[0848] wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0849] 262. The method of any of the preceding embodiments, wherein the antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

[0850] 263. The method of any of the preceding embodiments, wherein the antibody molecule comprises a VL comprising the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

[0851] 264. The method of any of the preceding embodiments, wherein the antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO: 286.

[0852] 265. A method as described in any of the preceding embodiments, wherein the antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of K.

[0853] 266. The method of any one of the preceding embodiments, wherein the antibody molecule is siberryizumab.

[0854] 267. The method of any one of the preceding embodiments, wherein the antibody molecule is administered no more than once a month.

[0855] 268. The method of any one of the preceding embodiments, wherein the antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg.

[0856] 269. The method of any one of the preceding embodiments, wherein the antibody molecule is administered once a month, once every two months, or once every three months.

[0857] 270. The method of any of the preceding embodiments, wherein the antibody molecule is administered repeatedly, e.g., at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 times.

[0858] 271. The method of any of the preceding embodiments, wherein the antibody molecule is administered monthly for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months.

[0859] 272. The method of any one of the preceding embodiments, wherein the antibody molecule is administered intravenously or subcutaneously.

[0860] 273. The method of any one of the preceding embodiments, wherein the antibody molecule is administered at a dose of 4 mg / kg, e.g., once monthly, and said administration results in an increase in eGFR within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months after said administration (e.g., after the first, second, or third administration).

[0861] 274. The method of any one of the preceding embodiments, wherein the antibody molecule is administered at a dose of 8 mg / kg, e.g., once monthly, and said administration results in an increase in eGFR within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months after said administration (e.g., after the first, second, or third administration).

[0862] 275. The method of embodiment 273 or 274, wherein eGFR is increased by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, e.g., within about 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months after the administration (e.g., after the first, second, or third administration).

[0863] 276. The method of any one of the preceding embodiments, wherein administration of the antibody molecule results in a decrease in serum IgA levels (e.g., compared to before the administration).

[0864] 277. The method of embodiment 276, wherein the reduction in serum IgA levels is maintained for at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months.

[0865] 278. The method of embodiment 276 or 277, wherein the serum IgA level is reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months after the administration (e.g., after the first, second, or third administration).

[0866] 279. The method of any one of embodiments 276-278, wherein the serum IgA level is reduced by at least 50, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 mg / dL, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months after the administration (e.g., after the first, second, or third administration).

[0867] 280. The method of any one of the preceding embodiments, wherein administration of the anti-APRIL antibody molecule results in a decrease in serum ag-IgA levels (eg, compared to before said administration).

[0868] 281. The method of embodiment 280, wherein the reduction in serum ag-IgA levels is maintained for at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months.

[0869] 282. The method of embodiment 280 or 281, wherein the serum ag-IgA level is reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months after the administration (e.g., after the first, second, or third administration).

[0870] 283. The method of any one of embodiments 280-282, wherein the ag-IgA comprises or is ag-IgA1.

[0871] 284. The method of any one of the preceding embodiments, wherein administration of the antibody molecule results in a decrease in serum IgG levels (e.g., compared to before the administration).

[0872] 285. The method of embodiment 284, wherein the reduction in serum IgG levels is maintained for at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months.

[0873] 286. The method of embodiment 284 or 285, wherein the serum IgG level is reduced by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 70%, 75%, 80%, 85%, or 90%, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months after the administration (e.g., after the first, second, or third administration).

[0874] 287. The method of any one of embodiments 284-286, wherein the serum IgG level is reduced by at least 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, or 800 mg / dL, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months after the administration (e.g., after the first, second, or third administration).

[0875] 288. The method of any one of the preceding embodiments, wherein administration of the antibody molecule results in a decrease in serum IgM levels (e.g., compared to before the administration).

[0876] 289. The method of embodiment 288, wherein the reduction in serum IgM levels is maintained for at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months.

[0877] 290. The method of embodiment 288 or 289, wherein the serum IgM level is reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months after the administration (e.g., after the first, second, or third administration).

[0878] 291. The method of any one of embodiments 288-290, wherein the serum IgM level is reduced by at least 10, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 mg / dL, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months after the administration (e.g., after the first, second, or third administration).

[0879] 292. The method of any one of the preceding embodiments, wherein administration of the anti-APRIL antibody molecule results in a decrease in uPCR (eg, compared to before said administration).

[0880] 293. The method of embodiment 288, wherein the reduction in uPCR is maintained for at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months.

[0881] 294. The method of embodiment 288 or 289, wherein the uPCR is reduced by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90%, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months after the administration (e.g., after the first, second, or third administration).

[0882] 295. The method of any one of the preceding embodiments, wherein the subject has or is at risk of having a disorder.

[0883] 296. The method of 295, wherein the condition is associated with decreased renal function.

[0884] 297. The method of...

Claims

1. An anti-APRIL antibody molecule for use in a method of improving renal function in a subject, The antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementary determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementary determining regions (LCDR1, LCDR2 and LCDR3), wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

2. The antibody molecule for use as claimed in claim 1, wherein said method reverses or prevents the progression of decreased renal function in said subject.

3. The antibody molecule for use as claimed in any one of claims 1 to 2, wherein the improved renal function comprises renal regeneration in the subject.

4. The antibody molecule for use according to any one of claims 1 to 3, wherein the improved renal function comprises an increase in the estimated glomerular filtration rate (eGFR) of the subject's kidney.

5. The antibody molecule for use according to any one of claims 1 to 4, wherein the improved renal function comprises a reduction in proteinuria in the kidneys of the subject.

6. The antibody molecule for use as described in any one of claims 1-5, wherein the method improves renal function in the subject within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months after administration of the antibody molecule (e.g., after the first, second or third administration).

7. The antibody molecule for use as claimed in any one of claims 1 to 6, wherein the method improves renal function in the subject after 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 administrations of the antibody molecule.

8. The antibody molecule for use as described in any one of claims 1-7, wherein the method improves renal function for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months.

9. An anti-APRIL antibody molecule for use in a method of preserving (e.g., maintaining or increasing) the estimated glomerular filtration rate (eGFR) of a subject's kidney, Optionally wherein the average eGFR over a period of at least twelve months after administration of the antibody molecule is greater than or equal to the subject's baseline eGFR, The antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementary determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementary determining regions (LCDR1, LCDR2 and LCDR3), wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

10. An anti-APRIL antibody molecule for use in a method of reducing proteinuria in the kidney of a subject, The antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementary determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementary determining regions (LCDR1, LCDR2 and LCDR3), wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

11. The antibody molecule for use as claimed in claim 10, wherein said reduction in proteinuria is determined by measuring the urine protein / creatinine ratio (uPCR), e.g. as described in Example 8.

12. The antibody molecule for use as claimed in any one of claims 10-11, wherein the method reduces proteinuria in the subject within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months after administration of the antibody molecule (e.g., after the first, second or third administration).

13. The antibody molecule for use according to claim 12, wherein the method reduces proteinuria in the subject within about 3 months after administration.

14. The antibody molecule for use according to claim 12, wherein said method reduces proteinuria in said subject within about 6 months after administration.

15. The antibody molecule for use according to claim 12, wherein the method reduces proteinuria in the subject within about 1 year after administration.

16. The antibody molecule for use according to claim 12, wherein the method reduces proteinuria in the subject within about 2 years after administration.

17. The antibody molecule for use according to claim 12, wherein the method reduces proteinuria in the subject within about 3 years after administration.

18. The antibody molecule for use according to claim 12, wherein the method reduces proteinuria in the subject within about 4 years after administration.

19. The antibody molecule for use as claimed in any one of claims 10 to 18, wherein the method reduces proteinuria in the subject after 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 administrations of the antibody molecule.

20. The antibody molecule for use as claimed in any one of claims 10-19, wherein the method reduces proteinuria for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months.

21. An anti-APRIL antibody molecule for use in a method of inducing renal recovery in a subject, The antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementary determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementary determining regions (LCDR1, LCDR2 and LCDR3), wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

22. An anti-APRIL antibody molecule for use in a method of inducing kidney regeneration in a subject, The antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementary determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementary determining regions (LCDR1, LCDR2 and LCDR3), wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

23. An anti-APRIL antibody molecule for use in a method of reducing an autoantibody response in a subject, The antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementary determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementary determining regions (LCDR1, LCDR2 and LCDR3), wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

24. An antibody molecule for use as claimed in any one of the preceding claims, wherein the antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

25. An antibody molecule for use as claimed in any preceding claim, wherein the antibody molecule comprises a VL comprising the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

26. The antibody molecule for use as claimed in any one of the preceding claims, wherein the antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO:

286.

27. The antibody molecule for use as claimed in any one of the preceding claims, wherein the antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of kappa.

28. The antibody molecule for use as claimed in any one of the preceding claims, wherein the antibody molecule is sibellumab.

29. The antibody molecule for use as claimed in any one of the preceding claims, wherein the antibody molecule is administered no more than once a month.

30. The antibody molecule for use as claimed in any one of the preceding claims, wherein the antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg.

31. The antibody molecule for use as claimed in any one of the preceding claims, wherein the antibody molecule is administered once a month, once every two months or once every three months.

32. The antibody molecule for use as claimed in any one of the preceding claims, wherein the antibody molecule is administered repeatedly, e.g. at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 times.

33. The antibody molecule for use as claimed in any one of the preceding claims, wherein the antibody molecule is administered monthly for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months.

34. The antibody molecule for use as claimed in any one of the preceding claims, wherein the antibody molecule is administered intravenously or subcutaneously.

35. The antibody molecule for use as claimed in any one of the preceding claims, wherein the antibody molecule is administered at a dose of 4 mg / kg, e.g., once a month, and the administration results in an increase in eGFR within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months after the administration (e.g., after the first, second or third administration).

36. The antibody molecule for use as claimed in any one of the preceding claims, wherein the antibody molecule is administered at a dose of 8 mg / kg, e.g., once a month, and the administration results in an increase in eGFR within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months after the administration (e.g., after the first, second or third administration).

37. The antibody molecule for use as described in claim 35 or 36, wherein the eGFR is increased by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%, e.g., within about 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months after the administration (e.g., after the first, second or third administration).

38. The antibody molecule for use as claimed in any preceding claim, wherein administration of the antibody molecule results in a reduction in serum IgA levels (eg compared to before said administration).

39. The antibody molecule for use as claimed in claim 38, wherein the reduction in serum IgA levels is maintained for at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months.

40. The antibody molecule for use as claimed in claim 38 or 39, wherein the serum IgA level is reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months after the administration (e.g., after the first, second or third administration).

41. The antibody molecule for use as described in any one of claims 38-40, wherein the serum IgA level is reduced by at least 50, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240 or 250 mg / dL, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months after the administration (e.g., after the first, second or third administration).

42. The antibody molecule for use as claimed in any preceding claim, wherein administration of the anti-APRIL antibody molecule results in a decrease in serum ag-IgA levels (eg compared to before said administration).

43. The antibody molecule for use as claimed in claim 42, wherein the reduction in serum ag-IgA levels is maintained for at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months.

44. The antibody molecule for use as claimed in claim 42 or 43, wherein the serum ag-IgA level is reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months after the administration (e.g., after the first, second or third administration).

45. The antibody molecule for use according to any one of claims 42 to 44, wherein the ag-IgA comprises ag-IgA1 or is ag-IgA1.

46. ​​The antibody molecule for use as claimed in any one of the preceding claims, wherein administration of the antibody molecule results in a reduction in serum IgG levels (eg compared to before said administration).

47. The antibody molecule for use as claimed in claim 46, wherein the reduction in serum IgG levels is maintained for at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months.

48. The antibody molecule for use as claimed in claim 46 or 47, wherein the serum IgG level is reduced by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 70%, 75%, 80%, 85% or 90%, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months after the administration (e.g., after the first, second or third administration).

49. The antibody molecule for use as described in any one of claims 46-48, wherein the serum IgG level is reduced by at least 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750 or 800 mg / dL, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months after the administration (e.g., after the first, second or third administration).

50. The antibody molecule for use as claimed in any one of the preceding claims, wherein administration of the antibody molecule results in a decrease in serum IgM levels (eg compared to before said administration).

51. The antibody molecule of claim 50, wherein the reduction in serum IgM levels is maintained for at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months.

52. The antibody molecule for use as claimed in claim 50 or 51, wherein the serum IgM level is reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months after the administration (e.g., after the first, second or third administration).

53. The antibody molecule for use as described in any one of claims 50-52, wherein the serum IgM level is reduced by at least 10, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90 or 95 mg / dL, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months after the administration (e.g., after the first, second or third administration).

54. The antibody molecule for use as claimed in any preceding claim, wherein administration of the anti-APRIL antibody molecule results in a decrease in uPCR (eg compared to before said administration).

55. The antibody molecule for use as described in claim 50, wherein the reduction in uPCR is maintained for at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months.

56. An antibody molecule for use as described in claim 50 or 51, wherein the uPCR is reduced by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% or 90%, e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months after the administration (e.g., after the first, second or third administration).

57. The antibody molecule for use as claimed in any one of the preceding claims, wherein the subject suffers from or is at risk of suffering from a disorder.

58. The antibody molecule for use according to 57, wherein the disorder is associated with decreased renal function.

59. The antibody molecule for use according to 57 or 58, wherein the disorder can be treated by improving renal function.

60. The antibody molecule for use as claimed in any one of claims 57 to 59, wherein the subject is at risk of renal failure.

61. The antibody molecule for use as claimed in any one of claims 57 to 60, wherein the disorder is a kidney disorder, such as chronic kidney disease (CKD).

62. The antibody molecule for use according to any one of claims 57 to 61, wherein the disorder is an autoimmune disorder, such as an autoantibody-associated disorder (eg, an IgM autoantibody-associated disorder).

63. The antibody molecule for use according to claim 62, wherein the autoantibody-associated disorder is primary membranous nephropathy, Goodpasture's disease or cold agglutinin disease.

64. The antibody molecule for use as claimed in any one of claims 57 to 63, wherein the disorder is an IgM-mediated disorder (eg, IgM neuropathy).

65. The antibody molecule for use according to any one of claims 57 to 64, wherein the disorder is glomerulonephritis.

66. An antibody molecule for use as described in any one of claims 57-65, wherein the disease or disorder is IgG nephropathy (IgAN), lupus nephritis, Henoch-Schonlein purpura (HSP, also known as IgA vasculitis (IgAV), e.g., with or without nephritis), vasculitis (e.g., ANCA-associated vasculitis or renal vasculitis), lupus, including systemic lupus erythematosus (SLE) and lupus nephritis, atypical hemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis (MPGN), primary membranous nephropathy, Goodpasture's disease, cold agglutinin disease, anti-MAG neuropathy, anti-GM1 neuropathy (multifocal motor neuropathy), Sjögren's syndrome, post-transplant IgA nephropathy, post-transplant glomerular disease relapse, or post-transplant IgA vasculitis.

67. The antibody molecule for use according to claim 66, wherein the disease or disorder is IgAN, such as primary IgAN or secondary IgAN.

68. The antibody molecule for use as claimed in claim 66, wherein the disease or disorder is Henoch-Schonlein purpura.

69. The antibody molecule for use as described in any one of claims 57-68, wherein the subject is a pediatric patient (e.g., a patient less than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 years of age; or a patient between the ages of 0-1, 1-2, 2-3, 3-4, 4-5, 5-10, 10-15, or 15-18 years of age).

70. The antibody molecule for use as described in claim 69, wherein the disease or condition is childhood IgA nephropathy, childhood Henoch-Schonlein purpura (HSP), childhood systemic lupus erythematosus (SLE), childhood lupus nephritis, childhood atypical hemolytic uremic syndrome (aHUS), childhood membranoproliferative glomerulonephritis (MPGN) or childhood ANCA-associated vasculitis.

71. The antibody molecule for use as described in any one of claims 66-70, wherein the subject exhibits arthritis symptoms, joint pain symptoms, gastrointestinal symptoms and / or dermatological symptoms.

72. The antibody molecule for use as claimed in any one of the preceding claims, wherein the subject is a human subject, such as a human patient.

73. The antibody molecule for use as claimed in any one of the preceding claims, wherein the subject is not immunocompromised.

74. The antibody molecule for use as claimed in claim 72 or 73, wherein the subject's serum IgG levels are not reduced relative to average healthy subjects (e.g., wherein the subject's serum IgG levels are at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% relative to average healthy subjects).

75. The antibody molecule for use as claimed in any one of the preceding claims, wherein said subject has proteinuria greater than or equal to uPCR 0.75 g / g or urine protein 1 g / day prior to said administration.

76. The antibody molecule for use of claim 75, wherein the subject has less than 0.1, 0.2, 0.3, 0.4, 0.5, 0.6 or 0.7 g / day of proteinuria after said administration (e.g., within 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months after said administration).

77. The antibody molecule for use as claimed in any preceding claim, wherein the subject has been treated with a different anti-APRIL antibody molecule.

78. The antibody molecule for use as claimed in any one of the preceding claims, further comprising administering to the subject a second therapeutic agent or treatment modality.

79. The antibody molecule for use as claimed in claim 78, wherein the second therapeutic agent comprises a TACI-IgG fusion protein (eg, teliximab).

80. The antibody molecule for use as claimed in claim 78, wherein the second therapeutic agent comprises a C1 inhibitor (eg, a C1s inhibitor, eg, sutimumab).

81. The antibody molecule for use as claimed in claim 78, wherein the second therapeutic agent is an anti-CD20 antibody (eg, rituximab).

82. An anti-APRIL antibody molecule for use in a method of treating IgA nephropathy, wherein the method comprises: In response to identifying a subject who would benefit from administration of an anti-APRIL antibody molecule, administering an effective amount of the anti-APRIL antibody molecule to the subject, wherein the anti-APRIL antibody molecule is administered no more than once a month, The benefits include one or more (e.g., two, three, or all) of the following: (i) APRIL levels are reduced by 90% or more within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline APRIL levels; (ii) a 60% or greater decrease in galactose-deficient IgA1 (Gd-IgA1) level within nine months of administration of the anti-APRIL antibody molecule compared to the subject's baseline Gd-IgA level; (iii) a 30% or greater decrease in 24 hour urine protein to creatinine ratio (uPCR) compared to the subject's baseline uPCR within nine months of administration of the anti-APRIL antibody molecule; or (iv) maintaining (e.g., maintaining or increasing) mean eGFR over a period of at least 12 months after administration of the anti-APRIL antibody molecule, compared to the subject's baseline eGFR; The anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementary determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementary determining regions (LCDR1, LCDR2 and LCDR3), and wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

83. The antibody molecule for use as claimed in claim 82, wherein the method further comprises identifying a subject who would benefit from administration of the anti-APRIL antibody molecule.

84. An anti-APRIL antibody molecule for use in a method of treating IgA nephropathy in a subject, wherein the anti-APRIL antibody molecule is to be administered no more than once a month, wherein the administering results in one or more (e.g., two, three, or all) of the following: (i) APRIL levels are reduced by 90% or more within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline APRIL levels; (ii) a 60% or greater decrease in galactose-deficient IgA1 (Gd-IgA1) level within nine months of administration of the anti-APRIL antibody molecule compared to the subject's baseline Gd-IgA level; (iii) a 30% or greater decrease in 24 hour urine protein to creatinine ratio (uPCR) compared to the subject's baseline uPCR within nine months of administration of the anti-APRIL antibody molecule; or (iv) maintaining (e.g., maintaining or increasing) mean eGFR over a period of at least 12 months after administration of the anti-APRIL antibody molecule, compared to the subject's baseline eGFR; The anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementary determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementary determining regions (LCDR1, LCDR2 and LCDR3), and wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

85. The antibody molecule for use as described in any one of claims 82-84, wherein the benefit comprises the following or the administration results in the following: (ii) a 60% or greater reduction in galactose-deficient IgA1 (Gd-IgA1) level within nine months of administration of the anti-APRIL antibody molecule compared to the subject's baseline Gd-IgA level; and (iv) maintaining (e.g., maintaining or increasing) mean eGFR over a period of at least 12 months after administration of the anti-APRIL antibody molecule, compared to the subject's baseline eGFR.

86. The antibody molecule for use as described in any one of claims 82-85, wherein APRIL levels are reduced by 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline APRIL levels.

87. The antibody molecule for use as described in any one of claims 82-86, wherein Gd-IgA1 levels are reduced by 65%, 70%, 75%, 85%, 90%, 95% or more within nine months of administration of the anti-APRIL antibody molecule compared to the subject's baseline Gd-IgA levels.

88. The antibody molecule for use as described in any one of claims 82-87, wherein 24-hour uPCR is reduced by 35%, 40%, 45%, 50%, 55%, 60% or more within nine months of administration of the anti-APRIL antibody molecule compared to the subject's baseline uPCR.

89. The antibody molecule for use as described in any one of claims 82-88, wherein the mean eGFR is maintained (e.g., maintained or increased) over a period of at least 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 months compared to the subject's baseline eGFR.

90. The antibody molecule for use according to any one of claims 82-89, wherein said benefit further comprises or said administration further results in: (v) a decrease in IgG levels compared to said subject's baseline IgG levels, optionally wherein the IgG levels are anti-gd-IgA1 IgG levels.

91. The antibody molecule for use as described in any one of claims 82-90, wherein the benefit further comprises or the administration further results in: (vi) a decrease in IgA levels compared to the subject's baseline IgA levels.

92. The antibody molecule for use as described in any one of claims 82-91, wherein the benefit further comprises or the administration further results in: (vii) a ratio of the mean eGFR over a period of 12 months after administration of the anti-APRIL antibody molecule to the expected mean eGFR over a period of 12 months if the anti-APRIL antibody molecule had not been administered to the subject of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15.

93. The antibody molecule for use as described in any one of claims 82-92, wherein the benefit also includes or the administration also results in: (vii) the eGFR does not decrease by 5%, 10%, 15% or more within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline eGFR.

94. The antibody molecule for use according to any one of claims 82-93, wherein the subject has one or more (e.g. two or all) of the following prior to administration of the anti-APRIL antibody molecule, (a) received angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for at least three months; (b) uPCR greater than 0.75 g / g or 24-hour urine protein (UP) level greater than 1.0 g / d; or (c) eGFR greater than 30 mL / min / 1.73 m 2 .

95. The antibody molecule for use according to any one of claims 82 to 94, wherein the anti-APRIL antibody molecule is administered intravenously at a dose of 2.0 mg / kg, 4.0 mg / kg or 8.0 mg / kg.

96. The antibody molecule for use according to any one of claims 82-95, wherein the subject has one or both of the following prior to administration of the anti-APRIL antibody molecule: (a) Proteinuria level greater than 2.0 g / day; or (b) eGFR equal to or less than 60 mL / min / 1.73 m 2 .

97. An anti-APRIL antibody molecule for use in a method of treating IgA nephropathy in a subject, The subject has or is identified as having: (a) a proteinuria level greater than 2.0 g / day, (b) an estimated glomerular filtration rate (eGFR) less than 60 mL / min / 1.73 m 2 or (c) both (a) and (b), The antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementary determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementary determining regions (LCDR1, LCDR2 and LCDR3), and wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, Optionally wherein the anti-APRIL antibody molecule is administered no more than once per month.

98. The antibody molecule for use as claimed in claim 97, wherein the anti-APRIL antibody molecule is administered in response to the identification of a subject having: (a) a proteinuria level greater than 2.0 g / day, (b) an estimated glomerular filtration rate (eGFR) less than 60 mL / min / 1.73 m 2 or (c) both (a) and (b).

99. The antibody molecule used as claimed in claim 97 or 98, wherein the method further comprises identifying a subject having: (a) a proteinuria level greater than 2.0 g / day, (b) an estimated glomerular filtration rate (eGFR) less than 60 mL / min / 1.73 m 2 or (c) both (a) and (b).

100. The antibody molecule for use as described in any one of claims 82-99, wherein the anti-APRIL antibody molecule comprises a VH, wherein the VH comprises the amino acid sequence of SEQ ID NO: 296, an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

101. The antibody molecule for use as described in any one of claims 82-100, wherein the anti-APRIL antibody molecule comprises a VL, wherein the VL comprises the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

102. The antibody molecule for use according to any one of claims 82 to 101, wherein the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO:

286.

103. The antibody molecule for use according to any one of claims 82 to 102, wherein the anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of kappa.

104. The antibody molecule for use according to any one of claims 82 to 103, wherein the anti-APRIL antibody molecule is siberryizumab.

105. The antibody molecule for use according to any one of claims 82-104, wherein the anti-APRIL antibody molecule is administered once a month, once every two months, once every three months or once every six months.

106. The antibody molecule for use according to any one of claims 82-105, wherein the anti-APRIL antibody molecule is administered once a month at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg.

107. The antibody molecule for use as described in any one of claims 82-106, wherein the anti-APRIL antibody molecule is administered repeatedly, for example at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 times.

108. The antibody molecule for use according to any one of claims 82-107, wherein the anti-APRIL antibody molecule is administered once a month for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months.

109. The antibody molecule for use according to any one of claims 82 to 108, wherein the anti-APRIL antibody molecule is administered intravenously or subcutaneously.

110. An anti-APRIL antibody molecule for use in a method of treating IgA nephropathy in a subject, wherein said subject has been administered a first anti-APRIL antibody molecule at a dose of at least 600 mg once every two weeks, and said administration of said first anti-APRIL antibody is discontinued, wherein the second anti-APRIL antibody molecule is administered no more than once a month, Optionally, the second anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3), and wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

111. The antibody molecule for use as claimed in claim 110, wherein in response to recognition of a subject who has been administered a first anti-APRIL antibody molecule at a dose of at least 600 mg once every two weeks, administration of the first anti-APRIL antibody molecule is stopped and the second anti-APRIL antibody molecule is administered.

112. The antibody molecule for use as claimed in claim 110 or 111, wherein the method further comprises: (a) identifying a subject who has been administered a first anti-APRIL antibody molecule at a dose of at least 600 mg once every two weeks; and (b) ceasing said administration of said first anti-APRIL antibody molecule.

113. The antibody molecule for use as described in any one of claims 110-112, wherein the second anti-APRIL antibody molecule comprises a VH, wherein the VH comprises the amino acid sequence of SEQ ID NO: 296, an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

114. The antibody molecule for use as described in any one of claims 110 to 113, wherein the second anti-APRIL antibody molecule comprises a VL, wherein the VL comprises the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

115. The antibody molecule for use according to any one of claims 110 to 114, wherein the second anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO:

286.

116. The antibody molecule for use according to any one of claims 110 to 115, wherein the second anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of kappa.

117. The antibody molecule for use according to any one of claims 110 to 116, wherein the second anti-APRIL antibody molecule is siberryizumab.

118. The antibody molecule for use according to any one of claims 110 to 117, wherein the second anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg.

119. The antibody molecule for use according to any one of claims 110 to 118, wherein the second anti-APRIL antibody molecule is administered once a month, once every two months, once every three months or once every six months.

120. The antibody molecule for use as described in any one of claims 110-119, wherein the second anti-APRIL antibody molecule is administered repeatedly, e.g., at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 times.

121. The antibody molecule for use as described in any one of claims 110-120, wherein the second anti-APRIL antibody molecule is administered once a month for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months.

122. The antibody molecule for use according to any one of claims 110 to 121, wherein the second anti-APRIL antibody molecule is administered intravenously or subcutaneously.

123. The antibody molecule for use as claimed in any one of claims 110 to 122, wherein the first anti-APRIL antibody molecule is BION-1301.

124. An anti-APRIL antibody molecule for use in a method for treating IgA nephropathy, wherein the method comprises administering a second anti-APRIL antibody molecule to a subject in need thereof at a dose of at least 600 mg once every two weeks, wherein a first anti-APRIL antibody molecule has been administered to said subject, and said administration of said first anti-APRIL antibody molecule is stopped, Optionally, the first anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3), and wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

125. The antibody molecule for use as claimed in claim 124, wherein the second anti-APRIL antibody molecule is administered in response to recognition by a subject to which the first anti-APRIL antibody molecule has been administered.

126. The antibody molecule for use as claimed in claim 124 or 125, wherein the method further comprises: (a) identifying a subject to whom a first anti-APRIL antibody molecule has been administered; and (b) ceasing said administration of said first anti-APRIL antibody molecule.

127. The antibody molecule for use as described in any one of claims 124-126, wherein the first anti-APRIL antibody molecule comprises a VH, wherein the VH comprises the amino acid sequence of SEQ ID NO: 296, an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

128. The antibody molecule for use as described in any one of claims 124-127, wherein the first anti-APRIL antibody molecule comprises a VL, wherein the VL comprises the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

129. The antibody molecule for use according to any one of claims 124 to 128, wherein the first anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO:

286.

130. The antibody molecule for use according to any one of claims 124 to 129, wherein the first anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of kappa.

131. The antibody molecule for use according to any one of claims 124 to 130, wherein the first anti-APRIL antibody molecule is siberryizumab.

132. The antibody molecule for use according to any one of claims 124 to 131, wherein the first anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg.

133. The antibody molecule for use according to any one of claims 124 to 132, wherein the first anti-APRIL antibody molecule is administered once a month, once every two months, once every three months or once every six months.

134. The antibody molecule for use as described in any one of claims 124-133, wherein the first anti-APRIL antibody molecule is administered repeatedly, for example at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 times.

135. The antibody molecule for use as described in any one of claims 124-134, wherein the first anti-APRIL antibody molecule is administered once a month for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months.

136. The antibody molecule for use according to any one of claims 124-135, wherein the first anti-APRIL antibody molecule is administered intravenously or subcutaneously.

137. The antibody molecule for use as claimed in any one of claims 124 to 136, wherein the second anti-APRIL antibody molecule is BION-1301.

138. An anti-APRIL antibody molecule for use in a method of treating IgA nephropathy in a subject, wherein the subject has been administered: (i) budesonide (e.g., once daily at a dose of 16 mg), (ii) atrasentan (e.g., once daily at a dose of 0.75 mg), (iii) dapagliflozin (e.g., once daily at a dose of 5 mg or 10 mg); or (iv) methylprednisolone (e.g., once daily), and the administration of (i) budesonide, (ii) atrasentan, (iii) dapagliflozin, or (iv) methylprednisolone is discontinued, wherein the anti-APRIL antibody molecule is administered no more than once a month, Optionally, the anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3), and wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

139. The antibody molecule for use as described in claim 138, wherein the anti-APRIL antibody molecule is administered in response to recognition of a subject who has been administered (i) budesonide (e.g., at a dose of 16 mg once daily), (ii) atrasentan (e.g., at a dose of 0.75 mg once daily), (iii) dapagliflozin (e.g., at a dose of 5 mg or 10 mg once daily); or (iv) methylprednisolone (e.g., once daily).

140. The antibody molecule for use as claimed in claim 138 or 139, wherein the method further comprises: (a) identifying subjects who have been administered (i) budesonide (e.g., at a dose of 16 mg once daily), (ii) atrasentan (e.g., at a dose of 0.75 mg once daily), (iii) dapagliflozin (e.g., at a dose of 5 mg or 10 mg once daily); or (iv) methylprednisolone (e.g., once daily); and (b) discontinuing said administration of (i) budesonide, (ii) atrasentan, (iii) dapagliflozin, or (iv) methylprednisolone.

141. An anti-APRIL antibody molecule for use in a method for treating IgA nephropathy, wherein the method comprises administering to a subject in need thereof (i) budesonide (e.g., at a dose of 16 mg once daily), (ii) atrasentan (e.g., at a dose of 0.75 mg once daily), (iii) dapagliflozin (e.g., at a dose of 5 mg or 10 mg once daily); or (iv) methylprednisolone (e.g., once daily), wherein said subject has been administered an anti-APRIL antibody molecule, and said administration of said anti-APRIL antibody molecule is stopped, Optionally, the first anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3), and wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

142. The antibody molecule for use as claimed in claim 151, wherein (i) budesonide, (ii) atrasentan, (iii) dapagliflozin or (iv) methylprednisolone is administered in response to recognition of a subject to which the anti-APRIL antibody molecule has been administered.

143. The antibody molecule for use as claimed in claim 151 or 152, wherein the method further comprises: (a) identifying a subject to whom an anti-APRIL antibody molecule has been administered; (b) ceasing said administration of said anti-APRIL antibody molecule.

144. The antibody molecule for use as described in any one of claims 138 to 143, wherein the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

145. The antibody molecule for use as described in any one of claims 138 to 144, wherein the anti-APRIL antibody molecule comprises a VL comprising the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

146. The antibody molecule for use according to any one of claims 138 to 145, wherein the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO:

286.

147. The antibody molecule for use as described in any one of claims 138 to 146, wherein the anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of kappa.

148. The antibody molecule for use according to any one of claims 138 to 147, wherein the anti-APRIL antibody molecule is siberryizumab.

149. The antibody molecule for use according to any one of claims 138 to 148, wherein the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg.

150. The antibody molecule for use according to any one of claims 138 to 149, wherein the anti-APRIL antibody molecule is administered once a month, once every two months, once every three months or once every six months.

151. The antibody molecule for use as described in any one of claims 138-150, wherein the anti-APRIL antibody molecule is administered repeatedly, for example at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 times.

152. The antibody molecule for use as described in any one of claims 138-151, wherein the anti-APRIL antibody molecule is administered once a month for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months.

153. The antibody molecule for use according to any one of claims 138 to 152, wherein the anti-APRIL antibody molecule is administered intravenously or subcutaneously.

154. An anti-APRIL antibody molecule for use in a method of selecting a subject to receive a therapy comprising the anti-APRIL antibody molecule, wherein the method comprises: (a) determining whether the subject develops one or more (e.g., two, three or all) of the following after monthly administration of the anti-APRIL antibody molecule: (i) APRIL levels are reduced by 90% or more within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline APRIL levels; (ii) a 60% or greater decrease in galactose-deficient IgA1 (Gd-IgA1) level within nine months of administration of the anti-APRIL antibody molecule compared to the subject's baseline Gd-IgA level; (iii) a 30% or greater decrease in 24 hour urine protein to creatinine ratio (uPCR) compared to the subject's baseline uPCR within nine months of administration of the anti-APRIL antibody molecule; or (iv) maintaining (e.g., maintaining or increasing) mean eGFR over a period of at least 12 months after administration of the anti-APRIL antibody molecule, compared to the subject's baseline eGFR; (b) selecting the subject based on determining that the subject will experience one or more (e.g., two, three, or all) of (i), (ii), (iii), or (iv) following monthly administration of the anti-APRIL antibody molecule, wherein the subject suffers from or is at risk of suffering from IgA nephropathy, The anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementary determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementary determining regions (LCDR1, LCDR2 and LCDR3), and wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

155. An anti-APRIL antibody molecule for use in a method of selecting a therapy comprising the anti-APRIL antibody molecule for a subject, wherein the method comprises: (a) determining whether the subject develops one or more (e.g., two, three or all) of the following after monthly administration of the anti-APRIL antibody molecule: (i) APRIL levels are reduced by 90% or more within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline APRIL levels; (ii) a 60% or greater decrease in galactose-deficient IgA1 (Gd-IgA1) level within nine months of administration of the anti-APRIL antibody molecule compared to the subject's baseline Gd-IgA level; (iii) a 30% or greater decrease in 24 hour urine protein to creatinine ratio (uPCR) compared to the subject's baseline uPCR within nine months of administration of the anti-APRIL antibody molecule; or (iv) maintaining (e.g., maintaining or increasing) mean eGFR over a period of at least 12 months after administration of the anti-APRIL antibody molecule, compared to the subject's baseline eGFR; (b) selecting the therapy comprising the anti-APRIL antibody molecule based on determining that the subject will experience one or more (e.g., two, three, or all) of (i), (ii), (iii), or (iv) following monthly administration of the anti-APRIL antibody molecule, wherein the subject suffers from or is at risk of suffering from IgA nephropathy, The anti-APRIL antibody molecule comprises a heavy chain variable region (VH) comprising three heavy chain complementary determining regions (HCDR1, HCDR2 and HCDR3) and a light chain variable region (VL) comprising three light chain complementary determining regions (LCDR1, LCDR2 and LCDR3), and wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or wherein the VH comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; a HCDR2 comprising the amino acid sequence of SEQ ID NO: 282; and a HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises a LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; a LCDR2 comprising the amino acid sequence of SEQ ID NO: 285; and a LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

156. The antibody molecule for use as described in claim 154 or 155, wherein the anti-APRIL antibody molecule comprises a VH, wherein the VH comprises the amino acid sequence of SEQ ID NO: 296, an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

157. The antibody molecule for use as described in any one of claims 154-156, wherein the anti-APRIL antibody molecule comprises a VL, wherein the VL comprises the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical thereto, or an amino acid sequence that differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

158. The antibody molecule for use according to any one of claims 154 to 157, wherein the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296 and a VL comprising the amino acid sequence of SEQ ID NO:

286.

159. The antibody molecule for use as described in any one of claims 154-158, wherein the anti-APRIL antibody molecule comprises a heavy chain constant region of IgG2 and a light chain constant region of kappa.

160. The antibody molecule for use according to any one of claims 154 to 159, wherein the anti-APRIL antibody molecule is siberryizumab.

161. The antibody molecule for use according to any one of claims 154-160, wherein the anti-APRIL antibody molecule is to be administered at a dose of 2 mg / kg, 4 mg / kg or 8 mg / kg.

162. The antibody molecule for use as described in any one of claims 154-161, wherein the anti-APRIL antibody molecule is to be administered once a month, once every two months, once every three months or once every six months.

163. The antibody molecule for use as described in any one of claims 154-162, wherein the anti-APRIL antibody molecule is to be repeatedly administered, for example at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 times.

164. The antibody molecule for use as described in any one of claims 154-163, wherein the anti-APRIL antibody molecule is to be administered once a month for a period of at least 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, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 or 36 months.

165. The antibody molecule for use according to any one of claims 154 to 164, wherein the anti-APRIL antibody molecule is to be administered intravenously or subcutaneously.

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