Antibody molecules directed against APRIL and uses thereof

Abstract

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

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS 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 which are incorporated herein by reference in their entireties.

[0002] Sequence Listing This application contains a Sequence Listing that has been submitted electronically in XML format and is incorporated herein by reference in its entirety. The XML copy was created on April 20, 2023, is named P2029-7047TW_SL.xml, and is 348,201 bytes in size. [Background technology]

[0003] IgA nephropathy is one of the most widespread chronic glomerular diseases worldwide. Conservative epidemiological estimates refer to a global prevalence of approximately 5-50 cases per million (children) and 10-40 cases per million (adults). The disease has a geographical prevalence, with a high prevalence in Asia and both Americas, and the disease burden is particularly high in the areas of Japan and China. Biopsy-confirmed cases of IgA nephropathy in Japan are estimated at approximately 350,000. In the United States, this estimate is approximately 100,000, making IgA nephropathy the first and most frequently diagnosed glomerular disease in adults. Although IgA nephropathy is a relatively indolent disease, it leads to end-stage renal disease (ESRD), i.e. renal failure, within 20-30 years in 20-50% of patients. Considering the need to confirm the disease by renal biopsy, a protocol performed in various ways in various clinical situations, these figures are likely to be greatly underreported. The disease has a complex pathogenesis with genetic, epidemiological, and possibly environmental components to the etiology, pathology, and progression of the disease. The disease also has a variety of clinical manifestations ranging from asymptomatic to end-stage renal disease (ESRD). IgA nephropathy typically occurs due to deposition of IgA in the form of immune complexes in the mesangium of the kidney. Currently, there are no disease-specific treatments that address the primary disease or progression.

[0004] There is a need to develop novel approaches to treat, prevent, and diagnose IgA nephropathy and other disorders that share similar disease mechanisms. Summary of the Invention

[0005] Thus, in certain aspects, the disclosure provides a method of improving renal function comprising administering an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule described herein) to a subject in need thereof, thereby improving renal function. In some embodiments, the method reverses or prevents the progression of reduced renal function in the subject. In some embodiments, the improved renal function comprises renal regeneration. In some embodiments, the improved renal function comprises increased estimated glomerular filtration rate (eGFR) in the kidney of the subject. In some embodiments, the improved renal function comprises reduced proteinuria in the kidney of the subject.

[0006] In one aspect, the 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 to the subject an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule described herein), thereby preserving (e.g., maintaining or increasing) eGFR in the kidney of the subject.

[0007] In some embodiments, the average eGFR over a period of at least 12 months after administration of the antibody molecule is equal to or greater than the subject's baseline eGFR. In some embodiments, the administration maintains the eGFR in the subject's kidney, e.g., the average eGFR over a period of at least 12 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 eGFR in the subject's kidney, e.g., the average eGFR over a period of at least 12 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 before administration of the antibody molecule.

[0008] In certain aspects, the disclosure provides a method of reducing renal proteinuria in a subject in need thereof, comprising administering to the subject an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule described herein), thereby reducing renal proteinuria in the subject. In some embodiments, the reduction in proteinuria is determined by measuring urinary protein / creatinine ratio (uPCR), e.g., as described herein.

[0009] In one aspect, the disclosure provides a method of inducing renal recovery in a subject in need thereof, the method comprising administering to the subject an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule described herein), thereby inducing renal recovery in the subject's kidney.

[0010] In one aspect, the disclosure provides a method of inducing kidney regeneration in a subject in need thereof, the method comprising administering to the subject an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule described herein), thereby inducing kidney regeneration in the subject's kidney.

[0011] In one aspect, the disclosure provides a method of reducing an autoantibody response in a subject in need thereof, comprising administering to the subject an anti-APRIL antibody molecule (e.g., an anti-APRIL antibody molecule described herein), thereby reducing the autoantibody response in the subject.

[0012] 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and / or VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or The VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and / or the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0013] In certain aspects, the disclosure also provides a method of treating a disorder, the method comprising administering an anti-APRIL antibody molecule as described herein to a subject in need thereof, wherein the antibody molecule is administered at a dose that reduces or is likely to reduce levels of abnormally glycosylated IgA (ag IgA), such as abnormally glycosylated IgA1 (ag IgA1), in the subject by at least 40%, thereby treating the disorder. In certain embodiments, the levels of ag IgA include or are levels of ag IgA1.

[0014] In certain embodiments, the level of ag IgA is reduced by at least 40% about 4 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 8 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 12 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 16 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% for a given period of time, e.g., at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months. In certain embodiments, the level of ag IgA is reduced by at least 50%. In certain embodiments, the level of ag IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In certain embodiments, the antibody molecule is administered as a single dose. In certain embodiments, the antibody molecule is administered as multiple doses. In some embodiments, the antibody molecule is administered subcutaneously. In some embodiments, the antibody molecule is administered intravenously.

[0015] In some embodiments, the disorder is an APRIL-associated disorder. In some embodiments, the disorder is associated with abnormal levels of total IgA. In some embodiments, the disorder is an ag IgA (e.g., ag IgA1)-associated disorder.

[0016] In some embodiments, the disorder is IgA nephropathy (IgAN). In some embodiments, the IgAN is familial IgAN. In some embodiments, the IgAN is adult IgAN. In some embodiments, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0017] In some embodiments, the disorder is chronic kidney disease (CKD) or a disorder associated with CKD. In some embodiments, the CKD is progressive CKD, e.g., an estimated glomerular filtration rate (eGFR) of about 30 or about 45 or greater.

[0018] In some embodiments, the disorder is Henoch-Schönlein purpura (HSP). In some embodiments, the disorder is cutaneous vasculitis or IgA vasculitis. In some embodiments, the disorder is IgA dermatitis, such as IgA bullous disease. In some embodiments, the disorder is Waldenstrom's macroglobulinemia (WM). In some embodiments, the disorder is lupus nephritis.

[0019] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has not or is not receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has or is identified as having a genomic susceptibility locus for a disorder, such as IgA nephropathy. In certain embodiments, the method further comprises determining whether the subject has a genomic susceptibility locus for the disorder, eg, IgA nephropathy.

[0020] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0021] In some embodiments, the level of ag IgA is determined in a sample from the subject. In some embodiments, the methods described herein further comprise determining the level of ag IgA in a sample from the subject. In some embodiments, the method further comprises determining the level of total IgA in the sample. In some embodiments, the method further comprises determining the level of IgM and / or IgG in the sample. In some embodiments, the method further comprises obtaining a sample from the subject. In some embodiments, the sample is a blood or serum sample.

[0022] In some embodiments, the method further comprises administering to the subject a second therapeutic agent or modality. In some embodiments, the second therapeutic agent or modality is a small molecule. In some embodiments, the second therapeutic agent or modality is an antibody molecule.

[0023] In certain embodiments, the subject has received, has received, 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 certain embodiments, the subject needs or is identified as needing to 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 certain embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the anti-APRIL antibody molecule.

[0024] In certain embodiments, administration of the anti-APRIL antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the anti-APRIL antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, 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 anti-APRIL antibody molecule.

[0025] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG for, 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 anti-APRIL antibody molecule.

[0026] In one aspect, the disclosure features a method of treating a disorder, the method including administering an anti-APRIL antibody molecule to a subject in need thereof, where the administration reduces the level of ag IgA (e.g., ag IgA1) in the subject by at least 40%, thereby treating the disorder. In an embodiment, the level of ag IgA includes or is the level of ag IgA1.

[0027] In certain embodiments, the level of ag IgA is reduced by at least 40% about 4 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 8 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 12 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 16 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% for a given period of time, e.g., at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months. In certain embodiments, the level of ag IgA is reduced by at least 50%. In certain embodiments, the level of ag IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In certain embodiments, the antibody molecule is administered as a single dose. In certain embodiments, the antibody molecule is administered as multiple doses. In some embodiments, the antibody molecule is administered subcutaneously. In some embodiments, the antibody molecule is administered intravenously.

[0028] In some embodiments, the disorder is an APRIL-associated disorder. In some embodiments, the disorder is associated with abnormal levels of total IgA. In some embodiments, the disorder is an ag IgA (e.g., ag IgA1)-associated disorder.

[0029] In some embodiments, the disorder is IgA nephropathy (IgAN). In some embodiments, the IgAN is familial IgAN. In some embodiments, the IgAN is adult IgAN. In some embodiments, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0030] In some embodiments, the disorder is chronic kidney disease (CKD) or a disorder associated with CKD. In some embodiments, the CKD is progressive CKD, e.g., an estimated glomerular filtration rate (eGFR) of about 30 or about 45 or greater.

[0031] In some embodiments, the disorder is Henoch-Schönlein purpura (HSP). In some embodiments, the disorder is cutaneous vasculitis or IgA vasculitis. In some embodiments, the disorder is IgA dermatitis, such as IgA bullous disease. In some embodiments, the disorder is Waldenstrom's macroglobulinemia (WM). In some embodiments, the disorder is lupus nephritis.

[0032] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has not or is not receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has or is identified as having a genomic susceptibility locus for a disorder, such as IgA nephropathy. In certain embodiments, the methods described herein further comprise the step of determining whether the subject has a genomic susceptibility locus for the disorder, eg, IgA nephropathy.

[0033] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0034] In some embodiments, the level of ag IgA is determined in a sample from the subject. In some embodiments, the method further comprises determining the level of ag IgA in a sample from the subject. In some embodiments, the method further comprises determining the level of total IgA in the sample. In some embodiments, the method further comprises determining the level of IgM and / or IgG in the sample. In some embodiments, the method further comprises obtaining a sample from the subject. In some embodiments, the sample is a blood or serum sample.

[0035] In some embodiments, the method further comprises administering to the subject a second therapeutic agent or modality. In some embodiments, the second therapeutic agent or modality is a small molecule. In some embodiments, the second therapeutic agent or modality is an antibody molecule.

[0036] In certain embodiments, the subject has received, has received, 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 certain embodiments, the subject needs or is identified as needing to 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 certain embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the anti-APRIL antibody molecule.

[0037] In certain embodiments, administration of the anti-APRIL antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the anti-APRIL antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, 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 anti-APRIL antibody molecule.

[0038] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG for, 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 anti-APRIL antibody molecule.

[0039] In yet another aspect, the disclosure features a method of treating a disorder, the method including administering to a subject in need thereof an anti-APRIL antibody molecule, where the antibody molecule is administered at a dosage (e.g., dose and frequency) that reduces or is likely to reduce levels of ag IgA (e.g., ag IgA1) in the subject by at least 40%, thereby treating the disorder. In an embodiment, the levels of ag IgA include or are levels of ag IgA1.

[0040] In certain embodiments, the level of ag IgA is reduced by at least 40% about 4 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 8 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 12 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 16 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% for a given period of time, e.g., at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months. In certain embodiments, the level of ag IgA is reduced by at least 50%. In certain embodiments, the level of ag IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In certain embodiments, the antibody molecule is administered as a single dose. In certain embodiments, the antibody molecule is administered as multiple doses. In some embodiments, the antibody molecule is administered subcutaneously. In some embodiments, the antibody molecule is administered intravenously.

[0041] In some embodiments, the disorder is an APRIL-associated disorder. In some embodiments, the disorder is associated with abnormal levels of total IgA. In some embodiments, the disorder is an ag IgA (e.g., ag IgA1)-associated disorder.

[0042] In some embodiments, the disorder is IgA nephropathy (IgAN). In some embodiments, the IgAN is familial IgAN. In some embodiments, the IgAN is adult IgAN. In some embodiments, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0043] In some embodiments, the disorder is chronic kidney disease (CKD) or a disorder associated with CKD. In some embodiments, the CKD is progressive CKD, e.g., an estimated glomerular filtration rate (eGFR) of about 30 or about 45 or greater.

[0044] In some embodiments, the disorder is Henoch-Schönlein purpura (HSP). In some embodiments, the disorder is cutaneous vasculitis or IgA vasculitis. In some embodiments, the disorder is IgA dermatitis, such as IgA bullous disease. In some embodiments, the disorder is Waldenstrom's macroglobulinemia (WM). In some embodiments, the disorder is lupus nephritis.

[0045] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has not or is not receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has or is identified as having a genomic susceptibility locus for a disorder, such as IgA nephropathy. In certain embodiments, the method further comprises determining whether the subject has a genomic susceptibility locus for the disorder, eg, IgA nephropathy.

[0046] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0047] In some embodiments, the level of ag IgA is determined in a sample from the subject. In some embodiments, the method further comprises determining the level of ag IgA in a sample from the subject. In some embodiments, the method further comprises determining the level of total IgA in the sample. In some embodiments, the method further comprises determining the level of IgM and / or IgG in the sample. In some embodiments, the method further comprises obtaining a sample from the subject. In some embodiments, the sample is a blood or serum sample.

[0048] In some embodiments, the method further comprises administering to the subject a second therapeutic agent or modality. In some embodiments, the second therapeutic agent or modality is a small molecule. In some embodiments, the second therapeutic agent or modality is an antibody molecule.

[0049] In certain embodiments, the subject has received, has received, 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 certain embodiments, the subject needs or is identified as needing to 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 certain embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the anti-APRIL antibody molecule.

[0050] In certain embodiments, administration of the anti-APRIL antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the anti-APRIL antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, 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 anti-APRIL antibody molecule.

[0051] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG for, 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 anti-APRIL antibody molecule.

[0052] In another aspect, the disclosure features a method of treating a disorder, the method including selecting a dose or dosage (e.g., dose and frequency) of an anti-APRIL antibody molecule, where administration of the antibody molecule at that dose or dosage reduces or is likely to reduce levels 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 disorder. In an embodiment, the level of ag IgA includes or is the level of ag IgA1.

[0053] In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 4 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 8 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 12 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 16 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% over a given period of time, for example at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 50%. In some embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of ag IgA by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the antibody molecule is administered as a single dose. In some embodiments, the antibody molecule is administered as multiple doses. In some embodiments, the antibody molecule is administered subcutaneously. In some embodiments, the antibody molecule is administered intravenously.

[0054] In some embodiments, the disorder is an APRIL-associated disorder. In some embodiments, the disorder is associated with abnormal levels of total IgA. In some embodiments, the disorder is an ag IgA (e.g., ag IgA1)-associated disorder.

[0055] In some embodiments, the disorder is IgA nephropathy (IgAN). In some embodiments, the IgAN is familial IgAN. In some embodiments, the IgAN is adult IgAN. In some embodiments, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0056] In some embodiments, the disorder is chronic kidney disease (CKD) or a disorder associated with CKD. In some embodiments, the CKD is progressive CKD, e.g., an estimated glomerular filtration rate (eGFR) of about 30 or about 45 or greater.

[0057] In some embodiments, the disorder is Henoch-Schönlein purpura (HSP). In some embodiments, the disorder is cutaneous vasculitis or IgA vasculitis. In some embodiments, the disorder is IgA dermatitis, such as IgA bullous disease. In some embodiments, the disorder is Waldenstrom's macroglobulinemia (WM). In some embodiments, the disorder is lupus nephritis.

[0058] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has not or is not receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has or is identified as having a genomic susceptibility locus for a disorder, such as IgA nephropathy. In certain embodiments, the method further comprises determining whether the subject has a genomic susceptibility locus for the disorder, eg, IgA nephropathy.

[0059] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0060] In some embodiments, the level of ag IgA is determined in a sample from the subject. In some embodiments, the method further comprises determining the level of ag IgA in a sample from the subject. In some embodiments, the method further comprises determining the level of total IgA in the sample. In some embodiments, the method further comprises determining the level of IgM and / or IgG in the sample. In some embodiments, the method further comprises obtaining a sample from the subject. In some embodiments, the sample is a blood or serum sample.

[0061] In some embodiments, the method further comprises administering to the subject a second therapeutic agent or modality. In some embodiments, the second therapeutic agent or modality is a small molecule. In some embodiments, the second therapeutic agent or modality is an antibody molecule.

[0062] In certain embodiments, the subject has received, has received, 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 certain embodiments, the subject needs or is identified as needing to 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 certain embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the anti-APRIL antibody molecule.

[0063] In certain embodiments, administration of the anti-APRIL antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the anti-APRIL antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, 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 anti-APRIL antibody molecule.

[0064] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG for, 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 anti-APRIL antibody molecule.

[0065] In one aspect, the disclosure features a method of treating a disorder, the method including, in response to a determination that administration of the anti-APRIL antibody molecule reduces or is likely to reduce levels of ag IgA (e.g., ag IgA1) in a subject in need thereof by at least 40%, administering an anti-APRIL antibody molecule to the subject, thereby treating the disorder. In an embodiment, the level of ag IgA includes or is the level of ag IgA1.

[0066] In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 4 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 8 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 12 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 16 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% over a given period of time, for example at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 50%. In some embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of ag IgA by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the antibody molecule is administered as a single dose. In some embodiments, the antibody molecule is administered as multiple doses. In some embodiments, the antibody molecule is administered subcutaneously. In some embodiments, the antibody molecule is administered intravenously.

[0067] In some embodiments, the disorder is an APRIL-associated disorder. In some embodiments, the disorder is associated with abnormal levels of total IgA. In some embodiments, the disorder is an ag IgA (e.g., ag IgA1)-associated disorder.

[0068] In some embodiments, the disorder is IgA nephropathy (IgAN). In some embodiments, the IgAN is familial IgAN. In some embodiments, the IgAN is adult IgAN. In some embodiments, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0069] In some embodiments, the disorder is chronic kidney disease (CKD) or a disorder associated with CKD. In some embodiments, the CKD is progressive CKD, e.g., an estimated glomerular filtration rate (eGFR) of about 30 or about 45 or greater.

[0070] In some embodiments, the disorder is Henoch-Schönlein purpura (HSP). In some embodiments, the disorder is cutaneous vasculitis or IgA vasculitis. In some embodiments, the disorder is IgA dermatitis, such as IgA bullous disease. In some embodiments, the disorder is Waldenstrom's macroglobulinemia (WM). In some embodiments, the disorder is lupus nephritis.

[0071] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has not or is not receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has or is identified as having a genomic susceptibility locus for a disorder, such as IgA nephropathy. In certain embodiments, the method further comprises determining whether the subject has a genomic susceptibility locus for the disorder, eg, IgA nephropathy.

[0072] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0073] In some embodiments, the level of ag IgA is determined in a sample from the subject. In some embodiments, the method further comprises determining the level of ag IgA in a sample from the subject. In some embodiments, the method further comprises determining the level of total IgA in the sample. In some embodiments, the method further comprises determining the level of IgM and / or IgG in the sample. In some embodiments, the method further comprises obtaining a sample from the subject. In some embodiments, the sample is a blood or serum sample.

[0074] In some embodiments, the method further comprises administering to the subject a second therapeutic agent or modality. In some embodiments, the second therapeutic agent or modality is a small molecule. In some embodiments, the second therapeutic agent or modality is an antibody molecule.

[0075] In certain embodiments, the subject has received, has received, 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 certain embodiments, the subject needs or is identified as needing to 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 certain embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the anti-APRIL antibody molecule.

[0076] In certain embodiments, administration of the anti-APRIL antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the anti-APRIL antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, 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 anti-APRIL antibody molecule.

[0077] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG for, 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 anti-APRIL antibody molecule.

[0078] In another aspect, the disclosure features a method of treating a disorder, the method including determining whether administration of an anti-APRIL antibody molecule will reduce or is likely to reduce levels of ag IgA (e.g., ag IgA1) in a subject in need thereof by at least 40%, and if the antibody molecule will reduce or is likely to reduce levels of ag IgA by at least 40%, initiating, continuing or maintaining administration of the antibody molecule. In an embodiment, the level of ag IgA includes or is the level of ag IgA1.

[0079] In certain embodiments, if the antibody molecule does not reduce or is not likely to reduce the levels of ag IgA by at least 40%, administration of the antibody molecule is terminated, discontinued, or modified. In certain embodiments, if the antibody molecule does not reduce or is not likely to reduce the levels of ag IgA by at least 40%, a different therapeutic agent or treatment modality is administered.

[0080] In certain embodiments, the level of ag IgA is reduced by at least 40% about 4 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 8 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 12 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 16 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% for a given period of time, e.g., at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months. In certain embodiments, the level of ag IgA is reduced by at least 50%. In certain embodiments, the level of ag IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In certain embodiments, the antibody molecule is administered as a single dose. In certain embodiments, the antibody molecule is administered as multiple doses. In some embodiments, the antibody molecule is administered subcutaneously. In some embodiments, the antibody molecule is administered intravenously.

[0081] In some embodiments, the disorder is an APRIL-associated disorder. In some embodiments, the disorder is associated with abnormal levels of total IgA. In some embodiments, the disorder is an ag IgA (e.g., ag IgA1)-associated disorder.

[0082] In some embodiments, the disorder is IgA nephropathy (IgAN). In some embodiments, the IgAN is familial IgAN. In some embodiments, the IgAN is adult IgAN. In some embodiments, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0083] In some embodiments, the disorder is chronic kidney disease (CKD) or a disorder associated with CKD. In some embodiments, the CKD is progressive CKD, e.g., an estimated glomerular filtration rate (eGFR) of about 30 or about 45 or greater.

[0084] In some embodiments, the disorder is Henoch-Schönlein purpura (HSP). In some embodiments, the disorder is cutaneous vasculitis or IgA vasculitis. In some embodiments, the disorder is IgA dermatitis, such as IgA bullous disease. In some embodiments, the disorder is Waldenstrom's macroglobulinemia (WM). In some embodiments, the disorder is lupus nephritis.

[0085] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has not or is not receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has or is identified as having a genomic susceptibility locus for a disorder, such as IgA nephropathy. In certain embodiments, the method further comprises determining whether the subject has a genomic susceptibility locus for the disorder, eg, IgA nephropathy.

[0086] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0087] In some embodiments, the level of ag IgA is determined in a sample from the subject. In some embodiments, the method further comprises determining the level of ag IgA in a sample from the subject. In some embodiments, the method further comprises determining the level of total IgA in the sample. In some embodiments, the method further comprises determining the level of IgM and / or IgG in the sample. In some embodiments, the method further comprises obtaining a sample from the subject. In some embodiments, the sample is a blood or serum sample.

[0088] In some embodiments, the method further comprises administering to the subject a second therapeutic agent or modality. In some embodiments, the second therapeutic agent or modality is a small molecule. In some embodiments, the second therapeutic agent or modality is an antibody molecule.

[0089] In certain embodiments, the subject has received, has received, 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 certain embodiments, the subject needs or is identified as needing to 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 certain embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the anti-APRIL antibody molecule.

[0090] In certain embodiments, administration of the anti-APRIL antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the anti-APRIL antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, 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 anti-APRIL antibody molecule.

[0091] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG for, 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 anti-APRIL antibody molecule.

[0092] In yet another aspect, the disclosure features a method of treating a disorder, the method including determining whether administration of a dose or dosage of an anti-APRIL antibody molecule will reduce or is likely to reduce levels of ag IgA1 (e.g., ag IgA1) in a subject in need thereof, and if the antibody molecule will reduce or is likely to reduce levels of ag IgA by at least 40% at that dose or dosage, then initiating, continuing or maintaining administration of the antibody molecule at that dose or dosage. In an embodiment, the level of ag IgA includes or is the level of ag IgA1.

[0093] In one embodiment, if the antibody molecule does not reduce or is not likely to reduce levels of ag IgA by at least 40% at that dose or dosage, administration of the antibody molecule at that dose or dosage is terminated, discontinued, or modified.

[0094] In certain embodiments, the level of ag IgA is reduced by at least 40% about 4 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 8 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 12 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 16 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% for a given period of time, e.g., at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months. In certain embodiments, the level of ag IgA is reduced by at least 50%. In certain embodiments, the level of ag IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In certain embodiments, the antibody molecule is administered as a single dose. In certain embodiments, the antibody molecule is administered as multiple doses. In some embodiments, the antibody molecule is administered subcutaneously. In some embodiments, the antibody molecule is administered intravenously.

[0095] In some embodiments, the disorder is an APRIL-associated disorder. In some embodiments, the disorder is associated with abnormal levels of total IgA. In some embodiments, the disorder is an ag IgA (e.g., ag IgA1)-associated disorder.

[0096] In some embodiments, the disorder is IgA nephropathy (IgAN). In some embodiments, the IgAN is familial IgAN. In some embodiments, the IgAN is adult IgAN. In some embodiments, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0097] In some embodiments, the disorder is chronic kidney disease (CKD) or a disorder associated with CKD. In some embodiments, the CKD is progressive CKD, e.g., an estimated glomerular filtration rate (eGFR) of about 30 or about 45 or greater.

[0098] In some embodiments, the disorder is Henoch-Schönlein purpura (HSP). In some embodiments, the disorder is cutaneous vasculitis or IgA vasculitis. In some embodiments, the disorder is IgA dermatitis, such as IgA bullous disease. In some embodiments, the disorder is Waldenstrom's macroglobulinemia (WM). In some embodiments, the disorder is lupus nephritis.

[0099] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has not or is not receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has or is identified as having a genomic susceptibility locus for a disorder, such as IgA nephropathy. In certain embodiments, the method further comprises determining whether the subject has a genomic susceptibility locus for the disorder, eg, IgA nephropathy.

[0100] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0101] In some embodiments, the level of ag IgA is determined in a sample from the subject. In some embodiments, the method further comprises determining the level of ag IgA in a sample from the subject. In some embodiments, the method further comprises determining the level of total IgA in the sample. In some embodiments, the method further comprises determining the level of IgM and / or IgG in the sample. In some embodiments, the method further comprises obtaining a sample from the subject. In some embodiments, the sample is a blood or serum sample.

[0102] In some embodiments, the method further comprises administering to the subject a second therapeutic agent or modality. In some embodiments, the second therapeutic agent or modality is a small molecule. In some embodiments, the second therapeutic agent or modality is an antibody molecule.

[0103] In certain embodiments, the subject has received, has received, 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 certain embodiments, the subject needs or is identified as needing to 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 certain embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the anti-APRIL antibody molecule.

[0104] In certain embodiments, administration of the anti-APRIL antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the anti-APRIL antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, 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 anti-APRIL antibody molecule.

[0105] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG for, 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 anti-APRIL antibody molecule.

[0106] In one aspect, the disclosure features a method of treating a disorder, the method comprising determining whether administration of a therapeutic agent or modality other than an anti-APRIL antibody molecule described herein will reduce or is likely to reduce the level of ag IgA by at least 40% in a subject in need thereof, and if the therapeutic agent or modality does not reduce or is likely to reduce the level of ag IgA by at least 40%, the method comprises administering an anti-APRIL antibody molecule described herein to the subject. In an embodiment, the antibody molecule is administered at a dose or dosage that reduces or is likely to reduce the level of ag IgA by at least 40% in the subject. In an embodiment, the level of ag IgA comprises or is the level of ag IgA1.

[0107] In certain embodiments, the therapeutic agent or modality reduces or is likely to reduce the level of ag IgA by at least 40% at about 4 weeks after the antibody molecule is administered. In certain embodiments, the therapeutic agent or modality reduces or is likely to reduce the level of ag IgA by at least 40% at about 8 weeks after the antibody molecule is administered. In certain embodiments, the therapeutic agent or modality reduces or is likely to reduce the level of ag IgA by at least 40% at about 12 weeks after the antibody molecule is administered. In certain embodiments, the therapeutic agent or modality reduces or is likely to reduce the level of ag IgA by at least 40% at about 16 weeks after the antibody molecule is administered. In certain embodiments, the therapeutic agent or modality reduces or is likely to reduce the level of ag IgA by at least 40% at a predetermined time period, e.g., at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months. In certain embodiments, the therapeutic agent or modality reduces or is likely to reduce the level of ag IgA by at least 50%. In certain embodiments, the therapeutic agent or modality reduces or is likely to reduce levels of ag IgA by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In certain embodiments, the therapeutic agent or modality is administered as a single dose. In certain embodiments, the therapeutic agent or modality is administered as multiple doses. In certain embodiments, the antibody molecule is administered subcutaneously. In certain embodiments, the antibody molecule is administered intravenously.

[0108] In certain embodiments, the disorder is associated with abnormal levels of total IgA, hi certain embodiments, the disorder is an ag IgA (e.g., ag IgA1) associated disorder.

[0109] In some embodiments, the disorder is IgA nephropathy (IgAN). In some embodiments, the IgAN is familial IgAN. In some embodiments, the IgAN is adult IgAN. In some embodiments, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0110] In some embodiments, the disorder is chronic kidney disease (CKD) or a disorder associated with CKD. In some embodiments, the CKD is progressive CKD, e.g., an estimated glomerular filtration rate (eGFR) of about 30 or about 45 or greater.

[0111] In some embodiments, the disorder is Henoch-Schönlein purpura (HSP). In some embodiments, the disorder is cutaneous vasculitis or IgA vasculitis. In some embodiments, the disorder is IgA dermatitis, such as IgA bullous disease. In some embodiments, the disorder is Waldenstrom's macroglobulinemia (WM). In some embodiments, the disorder is lupus nephritis.

[0112] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has not or is not receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has or is identified as having a genomic susceptibility locus for a disorder, such as IgA nephropathy. In certain embodiments, the method further comprises determining whether the subject has a genomic susceptibility locus for the disorder, eg, IgA nephropathy.

[0113] In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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 certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0114] In some embodiments, the level of ag IgA is determined in a sample from the subject. In some embodiments, the method further comprises determining the level of ag IgA in a sample from the subject. In some embodiments, the method further comprises determining the level of total IgA in the sample. In some embodiments, the method further comprises determining the level of IgM and / or IgG in the sample. In some embodiments, the method further comprises obtaining a sample from the subject. In some embodiments, the sample is a blood or serum sample.

[0115] In some embodiments, the method further comprises administering to the subject a second therapeutic agent or modality. In some embodiments, the second therapeutic agent or modality is a small molecule. In some embodiments, the second therapeutic agent or modality is an antibody molecule.

[0116] In certain embodiments, the subject has received, has received, 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 certain embodiments, the subject needs or is identified as needing to 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 certain embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the anti-APRIL antibody molecule.

[0117] In certain embodiments, administration of the anti-APRIL antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the anti-APRIL antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, 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 anti-APRIL antibody molecule.

[0118] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG for, 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 anti-APRIL antibody molecule.

[0119] In another aspect, the disclosure features a method of reducing levels of ag IgA (e.g., ag IgA1) in a subject, the method including 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 level of ag IgA in the subject by at least 40%, thereby reducing the level of ag IgA. In an embodiment, the level of ag IgA includes or is the level of ag IgA1.

[0120] In certain embodiments, the level of ag IgA is reduced by at least 40% about 4 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 8 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 12 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% about 16 weeks after the antibody molecule is administered. In certain embodiments, the level of ag IgA is reduced by at least 40% for a given period of time, e.g., at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months. In certain embodiments, the level of ag IgA is reduced by at least 50%. In certain embodiments, the level of ag IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In certain embodiments, the antibody molecule is administered as a single dose. In certain embodiments, the antibody molecule is administered as multiple doses. In some embodiments, the antibody molecule is administered subcutaneously. In some embodiments, the antibody molecule is administered intravenously.

[0121] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has not or is not receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has or is identified as having a genomic susceptibility locus for a disorder, such as IgA nephropathy. In certain embodiments, the method further comprises determining whether the subject has a genomic susceptibility locus for the disorder, eg, IgA nephropathy.

[0122] In some embodiments, the subject has or is identified as having an APRIL-related disorder. In some embodiments, the subject has or is identified as having a disorder associated with abnormal levels of total IgA. In some embodiments, the subject has or is identified as having a disorder associated with ag IgA (e.g. ag IgA1).

[0123] In some embodiments, the subject has or is identified as having IgA nephropathy (IgAN). In some embodiments, the IgAN is familial IgAN. In some embodiments, the IgAN is adult IgAN. In some embodiments, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0124] In some embodiments, the subject has or is identified as having chronic kidney disease (CKD) or a disorder related to CKD. In some embodiments, the CKD is progressive CKD, for example with an estimated glomerular filtration rate (eGFR) of about 30 or about 45 or greater.

[0125] In some embodiments, the subject has or is identified as having Henoch-Schönlein purpura (HSP). In some embodiments, the subject has or is identified as having cutaneous vasculitis or IgA vasculitis. In some embodiments, the subject has or is identified as having IgA dermatitis, such as IgA bullous disease. In some embodiments, the subject has or is identified as having Waldenstrom's macroglobulinemia (WM). In some embodiments, the subject has or is identified as having lupus nephritis.

[0126] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0127] In some embodiments, the level of ag IgA is determined in a sample from the subject. In some embodiments, the method further comprises determining the level of ag IgA in a sample from the subject. In some embodiments, the method further comprises determining the level of total IgA in the sample. In some embodiments, the method further comprises determining the level of IgM and / or IgG in the sample. In some embodiments, the method further comprises obtaining a sample from the subject. In some embodiments, the sample is a blood or serum sample.

[0128] In some embodiments, the method further comprises administering to the subject a second therapeutic agent or modality. In some embodiments, the second therapeutic agent or modality is a small molecule. In some embodiments, the second therapeutic agent or modality is an antibody molecule.

[0129] In certain embodiments, the subject has received, has received, 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 certain embodiments, the subject needs or is identified as needing to 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 certain embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the anti-APRIL antibody molecule.

[0130] In certain embodiments, administration of the anti-APRIL antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the anti-APRIL antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, 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 anti-APRIL antibody molecule.

[0131] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG for, 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 anti-APRIL antibody molecule.

[0132] In yet another aspect, the disclosure features a method of selecting an anti-APRIL antibody molecule for treating a disorder, the method including determining whether administration of the anti-APRIL antibody molecule will reduce or is likely to reduce levels 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 an embodiment, the level of ag IgA includes or is the level of ag IgA1.

[0133] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0134] In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 4 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 8 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 12 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 16 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% over a given period of time, for example at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 50%. In some embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of ag IgA by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the antibody molecule is administered as a single dose. In some embodiments, the antibody molecule is administered as multiple doses. In some embodiments, the antibody molecule is administered subcutaneously. In some embodiments, the antibody molecule is administered intravenously.

[0135] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has not or is not receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has or is identified as having a genomic susceptibility locus for a disorder, such as IgA nephropathy. In certain embodiments, the method further comprises determining whether the subject has a genomic susceptibility locus for the disorder, eg, IgA nephropathy.

[0136] In some embodiments, the subject has or is identified as having an APRIL-related disorder. In some embodiments, the subject has or is identified as having a disorder associated with abnormal levels of total IgA. In some embodiments, the subject has or is identified as having a disorder associated with ag IgA (e.g. ag IgA1).

[0137] In some embodiments, the subject has or is identified as having IgA nephropathy (IgAN). In some embodiments, the IgAN is familial IgAN. In some embodiments, the IgAN is adult IgAN. In some embodiments, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0138] In some embodiments, the subject has or is identified as having chronic kidney disease (CKD) or a disorder related to CKD. In some embodiments, the CKD is progressive CKD, for example with an estimated glomerular filtration rate (eGFR) of about 30 or about 45 or greater.

[0139] In some embodiments, the subject has or is identified as having Henoch-Schönlein purpura (HSP). In some embodiments, the subject has or is identified as having cutaneous vasculitis or IgA vasculitis. In some embodiments, the subject has or is identified as having IgA dermatitis, such as IgA bullous disease. In some embodiments, the subject has or is identified as having Waldenstrom's macroglobulinemia (WM). In some embodiments, the subject has or is identified as having lupus nephritis.

[0140] In some embodiments, the level of ag IgA is determined in a sample from the subject. In some embodiments, the method further comprises determining the level of ag IgA in a sample from the subject. In some embodiments, the method further comprises determining the level of total IgA in the sample. In some embodiments, the method further comprises determining the level of IgM and / or IgG in the sample. In some embodiments, the method further comprises obtaining a sample from the subject. In some embodiments, the sample is a blood or serum sample.

[0141] In certain embodiments, the subject has received, has received, 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 certain embodiments, the subject needs or is identified as needing to 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 certain embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the anti-APRIL antibody molecule.

[0142] In certain embodiments, administration of the anti-APRIL antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the anti-APRIL antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, 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 anti-APRIL antibody molecule.

[0143] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG for, 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 anti-APRIL antibody molecule.

[0144] In another aspect, the disclosure features a method of selecting a dose or dosage (e.g., dose and frequency) of an anti-APRIL antibody molecule for treating a disorder, the method including determining whether administration of the anti-APRIL antibody molecule at a dose or dosage will reduce or is likely to reduce levels of ag IgA (e.g., ag IgA1) in a subject in need thereof by at least 40%, thereby selecting the dose or dosage. In an embodiment, the level of ag IgA includes or is the level of ag IgA1.

[0145] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0146] In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 4 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 8 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 12 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 16 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% over a given period of time, for example at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 50%. In some embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of ag IgA by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the antibody molecule is administered as a single dose. In some embodiments, the antibody molecule is administered as multiple doses. In some embodiments, the antibody molecule is administered subcutaneously. In some embodiments, the antibody molecule is administered intravenously.

[0147] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has not or is not receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has or is identified as having a genomic susceptibility locus for a disorder, such as IgA nephropathy. In certain embodiments, the method further comprises determining whether the subject has a genomic susceptibility locus for the disorder, eg, IgA nephropathy.

[0148] In some embodiments, the subject has or is identified as having an APRIL-related disorder. In some embodiments, the subject has or is identified as having a disorder associated with abnormal levels of total IgA. In some embodiments, the subject has or is identified as having a disorder associated with ag IgA (e.g. ag IgA1).

[0149] In some embodiments, the subject has or is identified as having IgA nephropathy (IgAN). In some embodiments, the IgAN is familial IgAN. In some embodiments, the IgAN is adult IgAN. In some embodiments, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0150] In some embodiments, the subject has or is identified as having chronic kidney disease (CKD) or a disorder related to CKD. In some embodiments, the CKD is progressive CKD, for example with an estimated glomerular filtration rate (eGFR) of about 30 or about 45 or greater.

[0151] In some embodiments, the subject has or is identified as having Henoch-Schönlein purpura (HSP). In some embodiments, the subject has or is identified as having cutaneous vasculitis or IgA vasculitis. In some embodiments, the subject has or is identified as having IgA dermatitis, such as IgA bullous disease. In some embodiments, the subject has or is identified as having Waldenstrom's macroglobulinemia (WM). In some embodiments, the subject has or is identified as having lupus nephritis.

[0152] In some embodiments, the level of ag IgA is determined in a sample from the subject. In some embodiments, the method further comprises determining the level of ag IgA in a sample from the subject. In some embodiments, the method further comprises determining the level of total IgA in the sample. In some embodiments, the method further comprises determining the level of IgM and / or IgG in the sample. In some embodiments, the method further comprises obtaining a sample from the subject. In some embodiments, the sample is a blood or serum sample.

[0153] In certain embodiments, the subject has received, has received, 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 certain embodiments, the subject needs or is identified as needing to 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 certain embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the anti-APRIL antibody molecule.

[0154] In certain embodiments, administration of the anti-APRIL antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the anti-APRIL antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, 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 anti-APRIL antibody molecule.

[0155] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG for, 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 anti-APRIL antibody molecule.

[0156] In another aspect, the disclosure features a method of selecting a subject for treating a disorder, the method including determining whether administration of an anti-APRIL antibody molecule will reduce or is likely to reduce levels of ag IgA (e.g., ag IgA1) in a subject in need thereof by at least 40%, thereby selecting the subject. In an embodiment, the level of ag IgA includes or is the level of ag IgA1.

[0157] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0158] In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 4 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 8 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 12 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at about 16 weeks after the antibody molecule is administered. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% over a given period of time, for example at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce the level of ag IgA by at least 50%. In some embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of ag IgA by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the antibody molecule is administered as a single dose. In some embodiments, the antibody molecule is administered as multiple doses. In some embodiments, the antibody molecule is administered subcutaneously. In some embodiments, the antibody molecule is administered intravenously.

[0159] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has not or is not receiving a different therapeutic agent or treatment modality to treat the disorder. In some embodiments, the subject has or is identified as having a genomic susceptibility locus for a disorder, such as IgA nephropathy. In certain embodiments, the method further comprises determining whether the subject has a genomic susceptibility locus for the disorder, eg, IgA nephropathy.

[0160] In some embodiments, the subject has or is identified as having an APRIL-related disorder. In some embodiments, the subject has or is identified as having a disorder associated with abnormal levels of total IgA. In some embodiments, the subject has or is identified as having a disorder associated with ag IgA (e.g. ag IgA1).

[0161] In some embodiments, the subject has or is identified as having IgA nephropathy (IgAN). In some embodiments, the IgAN is familial IgAN. In some embodiments, the IgAN is adult IgAN. In some embodiments, the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0162] In some embodiments, the subject has or is identified as having chronic kidney disease (CKD) or a disorder related to CKD. In some embodiments, the CKD is progressive CKD, for example with an estimated glomerular filtration rate (eGFR) of about 30 or about 45 or greater.

[0163] In some embodiments, the subject has or is identified as having Henoch-Schönlein purpura (HSP). In some embodiments, the subject has or is identified as having cutaneous vasculitis or IgA vasculitis. In some embodiments, the subject has or is identified as having IgA dermatitis, such as IgA bullous disease. In some embodiments, the subject has or is identified as having Waldenstrom's macroglobulinemia (WM). In some embodiments, the subject has or is identified as having lupus nephritis.

[0164] In some embodiments, the level of ag IgA is determined in a sample from the subject. In some embodiments, the method further comprises determining the level of ag IgA in a sample from the subject. In some embodiments, the method further comprises determining the level of total IgA in the sample. In some embodiments, the method further comprises determining the level of IgM and / or IgG in the sample. In some embodiments, the method further comprises obtaining a sample from the subject. In some embodiments, the sample is a blood or serum sample.

[0165] In certain embodiments, the subject has received, has received, 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 certain embodiments, the subject needs or is identified as needing to 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 certain embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the anti-APRIL antibody molecule.

[0166] In certain embodiments, administration of the anti-APRIL antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the anti-APRIL antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, 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 anti-APRIL antibody molecule.

[0167] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG for, 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 anti-APRIL antibody molecule.

[0168] In another aspect, the disclosure features a method of treating IgA nephropathy, the method 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, where the subject has received or is about to 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 IgA nephropathy.

[0169] In certain embodiments, the method further comprises administering a vaccine to the subject prior to, concomitantly with, or following administration of the anti-APRIL antibody molecule.

[0170] In another aspect, the disclosure features a method of vaccinating a subject, the method including the step of administering an effective amount of a vaccine (e.g., a vaccine described herein) to a subject, where 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, thereby vaccinating the subject.

[0171] In certain embodiments, the method further comprises administering to the subject an anti-APRIL antibody molecule prior to, simultaneously with, or following administration of the vaccine.

[0172] In yet another aspect, the disclosure features a method of treating a disorder, the method including 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 level of IgM in the subject by at least a predetermined percentage, thereby treating the disorder.

[0173] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0174] In some embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of IgM by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In some embodiments, the antibody molecule is administered as a single dose. In some embodiments, the antibody molecule is administered as multiple doses. In some embodiments, the antibody molecule is administered subcutaneously. In some embodiments, the antibody molecule is administered intravenously.

[0175] In some embodiments, the subject is a human.In some embodiments, the subject has or is identified as having at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher IgM level than the IgM level in a reference subject, for example, a subject without a disorder, for example, a healthy or normal subject.In some embodiments, the subject has or is undergoing a different therapeutic agent or treatment modality for treating the disorder.In some embodiments, the subject has not or is not undergoing a different therapeutic agent or treatment modality for treating the disorder.

[0176] In some embodiments, the disorder is associated with abnormal levels of IgM. In some embodiments, the disorder is chronic kidney disease (CKD) or renal injury. In some embodiments, the disorder is fibrosis. In some embodiments, the disorder is IgM-mediated neuropathy, such as anti-MAG neuropathy or anti-GM1-related neuropathy. In some embodiments, the disorder is systemic lupus erythematosus (SLE). In some embodiments, the administration does not reduce or does not substantially reduce the level of IgG in the subject. In some embodiments, the administration reduces the level of IgG in the subject by no more than a predetermined percentage. In some embodiments, the administration reduces the level of IgG in the subject by at least a predetermined percentage.

[0177] In an embodiment, the level of IgM is determined in a sample from the subject. In an embodiment, the method comprises determining the level of IgM in a sample from the subject. In an embodiment, the method further comprises determining the level of total IgM in the sample. In an embodiment, the method further comprises determining the level of IgA (total IgA and / or ag IgA) and / or IgG in the sample. In an embodiment, the level of ag IgA comprises or is the level of ag IgA1. In an embodiment, the method further comprises obtaining a sample from the subject. In an embodiment, the sample is a blood or serum sample.

[0178] In some embodiments, the method further comprises administering to the subject a second therapeutic agent or modality. In some embodiments, the second therapeutic agent or modality is a small molecule. In some embodiments, the second therapeutic agent or modality is an antibody molecule.

[0179] In some embodiments, the subject has received, has received, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or within 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks, of administration of the antibody molecule. In some embodiments, the subject needs or is identified as needing to receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or within 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks, of administration of the antibody molecule. In some embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the antibody molecule.

[0180] In certain embodiments, administration of the antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, the subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to the vaccine after the antibody molecule is administered.

[0181] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or more after the antibody molecule is administered.

[0182] In another aspect, the disclosure features a method of reducing levels of IgM in a subject, the method including 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 level of IgM in the subject by at least a predetermined percentage, thereby reducing the level of IgM.

[0183] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0184] In some embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of IgM, for example by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% over a given period of time. In some embodiments, the antibody molecule is administered as a single dose. In some embodiments, the antibody molecule is administered as multiple doses. In some embodiments, the antibody molecule is administered subcutaneously. In some embodiments, the antibody molecule is administered intravenously.

[0185] In some embodiments, the subject is a human.In some embodiments, the subject has or is identified as having at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher IgM level than the IgM level in a reference subject, for example, a subject without a disorder, for example, a healthy or normal subject.In some embodiments, the subject has or is undergoing a different therapeutic agent or treatment modality for treating the disorder.In some embodiments, the subject has not or is not undergoing a different therapeutic agent or treatment modality for treating the disorder.

[0186] In some embodiments, the disorder is associated with abnormal levels of IgM. In some embodiments, the disorder is chronic kidney disease (CKD) or renal injury. In some embodiments, the disorder is fibrosis. In some embodiments, the disorder is IgM-mediated neuropathy, such as anti-MAG neuropathy or anti-GM1-related neuropathy. In some embodiments, the disorder is systemic lupus erythematosus (SLE). In some embodiments, the administration does not reduce or does not substantially reduce the level of IgG in the subject. In some embodiments, the administration reduces the level of IgG in the subject by no more than a predetermined percentage. In some embodiments, the administration reduces the level of IgG in the subject by at least a predetermined percentage.

[0187] In an embodiment, the level of IgM is determined in a sample from the subject. In an embodiment, the method comprises determining the level of IgM in a sample from the subject. In an embodiment, the method further comprises determining the level of total IgM in the sample. In an embodiment, the method further comprises determining the level of IgA (total IgA and / or ag IgA) and / or IgG in the sample. In an embodiment, the level of ag IgA comprises or is the level of ag IgA1. In an embodiment, the method further comprises obtaining a sample from the subject. In an embodiment, the sample is a blood or serum sample.

[0188] In some embodiments, the subject has received, has received, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or within 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks, of administration of the antibody molecule. In some embodiments, the subject needs or is identified as needing to receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or within 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks, of administration of the antibody molecule. In some embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the antibody molecule.

[0189] In certain embodiments, administration of the antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, the subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to the vaccine after the antibody molecule is administered.

[0190] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or more after the antibody molecule is administered.

[0191] In another aspect, the disclosure features a method of treating a disorder, the method including administering to a subject in need thereof an anti-APRIL antibody molecule, e.g., at a dose or dosage that reduces or has the potential to reduce IgA and IgM levels in the subject by at least a predetermined percentage, thereby treating the disorder.

[0192] In certain embodiments, the level of IgA includes or is a level of total IgA and / or ag IgA, hi certain embodiments, the level of ag IgA includes or is a level of ag IgA1.

[0193] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0194] In some embodiments, administration does not reduce or does not substantially reduce the level of IgG in the subject. In some embodiments, administration reduces the level of IgG in the subject by no more than a predetermined percentage. In some embodiments, administration reduces the level of IgG in the subject by at least a predetermined percentage.

[0195] In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of ag IgA, e.g., by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% over a given period of time. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of total IgA, e.g., by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% over a given period of time. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of IgM, e.g., by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% over a given period of time. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels 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 levels 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 period of time. In certain embodiments, the antibody molecule is administered as a single dose. In certain embodiments, the antibody molecule is administered as multiple doses. In certain embodiments, the antibody molecule is administered subcutaneously. In certain embodiments, the antibody molecule is administered intravenously.

[0196] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of IgM that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgM in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has received or is receiving a different therapeutic agent or therapeutic modality to treat the disorder. In certain embodiments, the subject has not received or is not receiving a different therapeutic agent or therapeutic modality to treat the disorder.

[0197] In some embodiments, the disorder is an APRIL-associated disorder. In some embodiments, the disorder is associated with abnormal levels of IgA (e.g., total IgA and / or ag IgA) and / or IgM, e.g., a disorder described herein. In some embodiments, the disorder is systemic lupus erythematosus (SLE). In some embodiments, the administration does not reduce or does not substantially reduce the level of IgG in the subject. In some embodiments, the administration reduces the level of IgG in the subject by no more than a predetermined percentage. In some embodiments, the administration reduces the level of IgG in the subject by at least a predetermined percentage. In some embodiments, the levels of IgA and / or IgM (and optionally IgG) are determined in a sample from the subject. In some embodiments, the method further comprises determining the level of ag IgA in the sample from the subject. In some embodiments, the method further comprises determining the level of total IgA in the sample. In some embodiments, the method further comprises determining the level of IgM in the sample. In some embodiments, the method further comprises determining the level of IgG in the sample. In some embodiments, the method further comprises obtaining a sample from the subject. In certain embodiments, the sample is a blood or serum sample.

[0198] In some embodiments, the method further comprises administering to the subject a second therapeutic agent or modality. In some embodiments, the second therapeutic agent or modality is a small molecule. In some embodiments, the second therapeutic agent or modality is an antibody molecule.

[0199] In some embodiments, the subject has received, has received, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or within 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks, of administration of the antibody molecule. In some embodiments, the subject needs or is identified as needing to receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or within 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks, of administration of the antibody molecule. In some embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the antibody molecule.

[0200] In certain embodiments, administration of the antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, the subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to the vaccine after the antibody molecule is administered.

[0201] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or more after the antibody molecule is administered.

[0202] In yet another aspect, the disclosure features a method of reducing IgA and IgM levels in a subject, the method including 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 IgA and IgM levels in the subject by at least a predetermined percentage, thereby reducing the IgA and IgM levels.

[0203] In certain embodiments, the level of IgA includes or is a level of total IgA and / or ag IgA, hi certain embodiments, the level of ag IgA includes or is a level of ag IgA1.

[0204] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0205] In some embodiments, administration does not reduce or does not substantially reduce the level of IgG in the subject. In some embodiments, administration reduces the level of IgG in the subject by no more than a predetermined percentage. In some embodiments, administration reduces the level of IgG in the subject by at least a predetermined percentage.

[0206] In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of ag IgA, e.g., by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% over a given period of time. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of total IgA, e.g., by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% over a given period of time. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of IgM, e.g., by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% over a given period of time. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels 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 levels 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 period of time. In certain embodiments, the antibody molecule is administered as a single dose. In certain embodiments, the antibody molecule is administered as multiple doses. In certain embodiments, the antibody molecule is administered subcutaneously. In certain embodiments, the antibody molecule is administered intravenously.

[0207] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of IgM that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgM in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has received or is receiving a different therapeutic agent or therapeutic modality to treat the disorder. In certain embodiments, the subject has not received or is not receiving a different therapeutic agent or therapeutic modality to treat the disorder.

[0208] In some embodiments, the disorder is an APRIL-associated disorder. In some embodiments, the disorder is associated with abnormal levels of IgA (e.g., total IgA and / or ag IgA) and / or IgM, e.g., a disorder described herein. In some embodiments, the disorder is systemic lupus erythematosus (SLE). In some embodiments, the administration does not reduce or does not substantially reduce the level of IgG in the subject. In some embodiments, the administration reduces the level of IgG in the subject by no more than a predetermined percentage. In some embodiments, the administration reduces the level of IgG in the subject by at least a predetermined percentage. In some embodiments, the levels of IgA and / or IgM (and optionally IgG) are determined in a sample from the subject. In some embodiments, the method further comprises determining the level of ag IgA in the sample from the subject. In some embodiments, the method further comprises determining the level of total IgA in the sample. In some embodiments, the method further comprises determining the level of IgM in the sample. In some embodiments, the method further comprises determining the level of IgG in the sample. In some embodiments, the method further comprises obtaining a sample from the subject. In certain embodiments, the sample is a blood or serum sample.

[0209] In some embodiments, the method further comprises administering to the subject a second therapeutic agent or modality. In some embodiments, the second therapeutic agent or modality is a small molecule. In some embodiments, the second therapeutic agent or modality is an antibody molecule.

[0210] In some embodiments, the subject has received, has received, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or within 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks, of administration of the antibody molecule. In some embodiments, the subject needs or is identified as needing to receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or within 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks, of administration of the antibody molecule. In some embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the antibody molecule.

[0211] In certain embodiments, administration of the antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, the subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to the vaccine after the antibody molecule is administered.

[0212] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or more after the antibody molecule is administered.

[0213] In another aspect, the disclosure features a method of treating a disorder, the method including administering to a subject in need thereof an effective amount of an anti-APRIL antibody molecule, the disorder being: (a) progressive chronic kidney disease (CKD) (e.g., with an eGFR equal to or greater than about 30 or 45); (b) post-transplant IgAN; (c) pediatric IgAN; (d) Henoch-Schönlein purpura (HSP) or cutaneous vasculitis; (e) IgAN with crescentic glomerulonephritis (GN); (f) IgA vasculitis; (g) IgA dermatitis; (h) IgM-mediated neuropathy (anti-MAG or anti-GM1); (i) Waldenström macroglobulinemia (WM); or (j) Lupus nephritis.

[0214] In some embodiments, the anti-APRIL antibody molecule is an anti-APRIL antibody molecule described herein. In some embodiments, the anti-APRIL antibody molecule is an 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. In certain embodiments, the anti-APRIL antibody molecule is selected from the group consisting of 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.

[0215] In some embodiments, the administration reduces or is likely to reduce IgA in the subject. In some embodiments, the administration reduces or is likely to reduce IgM in the subject. In some embodiments, the level of IgA includes or is the level of total IgA and / or ag IgA. In some embodiments, the level of ag IgA includes or is the level of ag IgA1.

[0216] In some embodiments, administration does not reduce or does not substantially reduce the level of IgG in the subject. In some embodiments, administration reduces the level of IgG in the subject by no more than a predetermined percentage. In some embodiments, administration reduces the level of IgG in the subject by at least a predetermined percentage.

[0217] In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of ag IgA, e.g., by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% over a given period of time. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of total IgA, e.g., by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% over a given period of time. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels of IgM, e.g., by at least 20%, 25%, 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% over a given period of time. In certain embodiments, the anti-APRIL antibody molecule reduces or is likely to reduce levels 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 levels 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 period of time. In certain embodiments, the antibody molecule is administered as a single dose. In certain embodiments, the antibody molecule is administered as multiple doses. In certain embodiments, the antibody molecule is administered subcutaneously. In certain embodiments, the antibody molecule is administered intravenously.

[0218] In some embodiments, the subject is a human. In some embodiments, the subject has or is identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has or is identified as having a level of IgM that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgM in a reference subject, such as a subject without a disorder, such as a healthy or normal subject. In some embodiments, the subject has received or is receiving a different therapeutic agent or therapeutic modality to treat the disorder. In certain embodiments, the subject has not received or is not receiving a different therapeutic agent or therapeutic modality to treat the disorder.

[0219] In some embodiments, the disorder is progressive chronic kidney disease (CKD) (e.g., with an eGFR equal to or greater than about 30 or 45). In some embodiments, the disorder is post-transplant IgAN. In some embodiments, the disorder is pediatric IgAN. In some embodiments, the disorder is Henoch-Schönlein purpura (HSP) or cutaneous vasculitis. In some embodiments, the disorder is IgAN with crescentic glomerulonephritis (GN). In some embodiments, the disorder is IgA vasculitis. In some embodiments, the disorder is IgA dermatitis. In some embodiments, the disorder is IgM-mediated neuropathy (anti-MAG or anti-GM1). In some embodiments, the disorder is Waldenstrom's macroglobulinemia (WM). In some embodiments, the disorder is lupus nephritis.

[0220] In some embodiments, the method further comprises administering to the subject a second therapeutic agent or modality. In some embodiments, the second therapeutic agent or modality is a small molecule. In some embodiments, the second therapeutic agent or modality is an antibody molecule.

[0221] In some embodiments, the subject has received, has received, or will receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or within 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks, of administration of the antibody molecule. In some embodiments, the subject needs or is identified as needing to receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or within 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks, of administration of the antibody molecule. In some embodiments, the subject receives a vaccine prior to, concomitantly with, or following administration of the antibody molecule.

[0222] In certain embodiments, administration of the antibody molecule reduces the subject's ability to have 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%. In certain embodiments, administration of the antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine. In certain embodiments, the subject has or maintains an effective (e.g., protective) antigen-specific serum IgG and / or IgA response to the vaccine after the antibody molecule is administered.

[0223] In some embodiments, the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®). In some embodiments, the subject has or maintains effective (e.g., protective) levels (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 weeks or more after the antibody molecule is administered.

[0224] In another aspect, the disclosure features a method of treating a disorder associated with an autoantigen, the method including administering to a subject in need thereof an effective amount of a therapeutic agent or therapeutic modality, where the administration reduces or is likely to reduce levels of the autoantigen in the subject by at least a predetermined percentage.

[0225] In some embodiments, the subject is a human. In some embodiments, the subject has or has been identified as having an APRIL-associated disorder.

[0226] In some embodiments, the level of the autoantigen is determined in a sample from the subject. In some embodiments, the method further comprises obtaining the sample from the subject. In some embodiments, the sample is a blood or serum sample.

[0227] In some embodiments, the method further comprises administering to the subject a second therapeutic agent or modality. In some embodiments, the second therapeutic agent or modality is a small molecule. In some embodiments, the second therapeutic agent or modality is an antibody molecule.

[0228] In an aspect, the present disclosure provides a method of treating IgA nephropathy, comprising: responsive to identifying a subject who will benefit from administration of the anti-APRIL antibody molecule, administering to the subject an effective amount of the anti-APRIL antibody molecule; the anti-APRIL antibody molecule is administered no more than once a month; Profit is less than (i) a 90% or greater reduction in the level of APRIL within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of APRIL; (ii) a 60% or greater reduction in the level of galactosyl IgA1 (Gd-IgA1) within 9 months of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of Gd-IgA; (iii) a 30% or greater reduction in 24-hour urinary protein creatinine ratio (uPCR) within 9 months of administration of the anti-APRIL antibody molecule compared to the subject's baseline uPCR; or (iv) preserving (e.g., maintaining or increasing) the mean eGFR over a period of at least 12 months following administration of the anti-APRIL antibody molecule compared to the subject's baseline eGFR; Thereby, a method is featured for treating IgA nephropathy.

[0229] In certain 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or The VH comprises an HCDR1 having the amino acid sequence of SEQ ID NO: 17, an HCDR2 having the amino acid sequence of SEQ ID NO: 282, and an HCDR3 having the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 having the amino acid sequence of SEQ ID NO: 280, an LCDR2 having the amino acid sequence of SEQ ID NO: 285, and an LCDR3 having the amino acid sequence of SEQ ID NO: 16.

[0230] In an embodiment, the subject's baseline level of APRIL is the level of APRIL before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In an embodiment, the subject's baseline level of Gd-IgA is the level of Gd-IgA before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In an embodiment, the subject's baseline uPCR is uPCR before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In an embodiment, the subject's baseline eGFR is eGFR before administration of the anti-APRIL antibody molecule (e.g., before the first administration).

[0231] In certain embodiments, the method further comprises identifying a subject that would benefit from administration of the anti-APRIL antibody molecule.

[0232] In one embodiment, the benefit includes (ii) a 60% or greater reduction in levels of galactosyl IgA1 (Gd-IgA1) within 9 months of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of Gd-IgA, and (iv) preserving (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.

[0233] In some embodiments, the level of APRIL is 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 level of APRIL. In some embodiments, the level of Gd-IgA1 is 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 level of Gd-IgA. In some embodiments, the 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 certain embodiments, the mean eGFR is preserved (e.g., maintained or increased) compared to the subject's baseline eGFR for a period of at least 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 months.

[0234] In some embodiments, the benefit further comprises (v) a reduction in the level of IgG compared to the subject's baseline level of IgG, optionally the level of IgG being an anti-gd-IgA1 IgG. In some embodiments, the benefit further comprises (vi) a reduction in the level of IgA compared to the subject's baseline level of IgA. In some embodiments, the benefit further comprises (vii) a ratio of the average eGFR over a 12-month period following administration of the anti-APRIL antibody molecule to the expected average eGFR over that 12-month period if the subject had not been administered the anti-APRIL antibody molecule of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. In some embodiments, the benefit further comprises (vii) not having a decrease in eGFR of 5%, 10%, 15%, or more within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline eGFR.

[0235] In certain embodiments, the subject has the following, prior to administration of the anti-APRIL antibody molecule: (a) receipt of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) for at least 3 months; (b) a uPCR of greater than 0.75 g / g or a 24-hour urinary protein (UP) level of greater than 1.0 g / day; or (c) a urinary protein level of greater than 30 mL / min / 1.73 m 2 In certain embodiments, the subject has one or more (e.g., two or all) of the following, prior to administration of the anti-APRIL antibody molecule: (a) a proteinuria level of greater than 2.0 g / day, or (b) an eGFR of 60 mL / min / 1.73 m 2 Having one or both of the following eGFR:

[0236] In certain embodiments, the anti-APRIL antibody molecule comprises a VH comprising an amino acid sequence of SEQ ID NO: 296, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence differing therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In certain embodiments, the anti-APRIL antibody molecule comprises a VL comprising an amino acid sequence of SEQ ID NO: 286, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence differing therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In certain embodiments, the anti-APRIL antibody molecule comprises a VH comprising an amino acid sequence of SEQ ID NO: 296 and a VL comprising an amino acid sequence of SEQ ID NO: 286. In certain embodiments, the anti-APRIL antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region. In one embodiment, the anti-APRIL antibody molecule is sibeprenlimab.

[0237] In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg, or 8 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered once a month, once every two months, once every three months, or once every six months. In certain embodiments, 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 certain embodiments, 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 some embodiments, the anti-APRIL antibody molecule is administered intravenously or subcutaneously. In some embodiments, the anti-APRIL antibody molecule is administered intravenously. In some embodiments, the anti-APRIL antibody molecule is administered subcutaneously.

[0238] In an aspect, the disclosure provides a method of treating IgA nephropathy, comprising administering to a subject in need thereof an effective amount of an anti-APRIL antibody molecule, the anti-APRIL antibody molecule is administered no more than once a month; The administration is as follows: (i) a 90% or greater reduction in the level of APRIL within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of APRIL; (ii) a 60% or greater reduction in the level of galactosyl IgA1 (Gd-IgA1) within 9 months of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of Gd-IgA; (iii) a 30% or greater reduction in 24-hour urinary protein creatinine ratio (uPCR) within 9 months of administration of the anti-APRIL antibody molecule compared to the subject's baseline uPCR; or (iv) preserving (e.g., maintaining or increasing) the mean eGFR over a period of at least 12 months following administration of the anti-APRIL antibody molecule compared to the subject's baseline eGFR; thereby treating IgA nephropathy.

[0239] In certain 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or The VH comprises an HCDR1 having the amino acid sequence of SEQ ID NO: 17, an HCDR2 having the amino acid sequence of SEQ ID NO: 282, and an HCDR3 having the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 having the amino acid sequence of SEQ ID NO: 280, an LCDR2 having the amino acid sequence of SEQ ID NO: 285, and an LCDR3 having the amino acid sequence of SEQ ID NO: 16.

[0240] In an embodiment, the subject's baseline level of APRIL is the level of APRIL before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In an embodiment, the subject's baseline level of Gd-IgA is the level of Gd-IgA before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In an embodiment, the subject's baseline uPCR is uPCR before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In an embodiment, the subject's baseline eGFR is eGFR before administration of the anti-APRIL antibody molecule (e.g., before the first administration).

[0241] In one embodiment, the benefit includes (ii) a 60% or greater reduction in levels of galactosyl IgA1 (Gd-IgA1) within 9 months of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of Gd-IgA, and (iv) preserving (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, or the administration results in (ii) and (iv).

[0242] In some embodiments, the level of APRIL is 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 level of APRIL. In some embodiments, the level of Gd-IgA1 is 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 level of Gd-IgA. In some embodiments, the 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 certain embodiments, the mean eGFR is preserved (e.g., maintained or increased) compared to the subject's baseline eGFR for a period of at least 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 months.

[0243] In certain embodiments, the administration further results in (v) a reduction in the level of IgG compared to the subject's baseline level of IgG, optionally the level of IgG being an anti-gd-IgA1 IgG. In certain embodiments, the administration further results in (vi) a reduction in the level of IgA compared to the subject's baseline level of IgA. In certain embodiments, the administration further results in (vii) a ratio of the average eGFR over a 12-month period after administration of the anti-APRIL antibody molecule to the expected average eGFR over that 12-month period if the subject had not been administered the anti-APRIL antibody molecule of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. In certain embodiments, the administration further results in (vii) not having a decrease in eGFR of 5%, 10%, 15%, or more within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline eGFR.

[0244] In certain embodiments, the subject has the following, prior to administration of the anti-APRIL antibody molecule: (a) receipt of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) for at least 3 months; (b) a uPCR of greater than 0.75 g / g or a 24-hour urinary protein (UP) level of greater than 1.0 g / day; or (c) a urinary protein level of greater than 30 mL / min / 1.73 m 2 In certain embodiments, the subject has one or more (e.g., two or all) of the following, prior to administration of the anti-APRIL antibody molecule: (a) a proteinuria level of greater than 2.0 g / day, or (b) an eGFR of 60 mL / min / 1.73 m 2 Having one or both of the following eGFR:

[0245] In certain embodiments, the anti-APRIL antibody molecule comprises a VH comprising an amino acid sequence of SEQ ID NO: 296, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence differing therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In certain embodiments, the anti-APRIL antibody molecule comprises a VL comprising an amino acid sequence of SEQ ID NO: 286, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence differing therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In certain embodiments, the anti-APRIL antibody molecule comprises a VH comprising an amino acid sequence of SEQ ID NO: 296 and a VL comprising an amino acid sequence of SEQ ID NO: 286. In certain embodiments, the anti-APRIL antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region. In one embodiment, the anti-APRIL antibody molecule is sibeprenlimab.

[0246] In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg, or 8 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered once a month, once every two months, once every three months, or once every six months. In certain embodiments, 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 certain embodiments, 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 some embodiments, the anti-APRIL antibody molecule is administered intravenously or subcutaneously. In some embodiments, the anti-APRIL antibody molecule is administered intravenously. In some embodiments, the anti-APRIL antibody molecule is administered subcutaneously.

[0247] In an aspect, the disclosure provides a method of treating IgA nephropathy, comprising administering to a subject in need thereof an effective amount of an anti-APRIL antibody molecule, Subjects were randomly assigned to: (a) have a proteinuria level of >2.0 g / day; (b) have a proteinuria level of >60 mL / min / 1.73 m 2 or (c) having or identified as having both (a) and (b); where appropriate, the anti-APRIL antibody molecule is administered no more than once a month; thereby treating IgA nephropathy.

[0248] In certain 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or The VH comprises an HCDR1 having the amino acid sequence of SEQ ID NO: 17, an HCDR2 having the amino acid sequence of SEQ ID NO: 282, and an HCDR3 having the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 having the amino acid sequence of SEQ ID NO: 280, an LCDR2 having the amino acid sequence of SEQ ID NO: 285, and an LCDR3 having the amino acid sequence of SEQ ID NO: 16.

[0249] In certain embodiments, the anti-APRIL antibody molecule is administered to treat: (a) a proteinuria level of greater than 2.0 g / day; (b) a proteinuria level of greater than 60 mL / min / 1.73 m 2 or (c) upon identification of a subject having both (a) and (b).

[0250] In an embodiment, the method comprises the steps of: (a) a proteinuria level of greater than 2.0 g / day; (b) a proteinuria level of greater than 60 mL / min / 1.73 m 2 or (c) identifying subjects having both (a) and (b).

[0251] In certain embodiments, the anti-APRIL antibody molecule comprises a VH comprising an amino acid sequence of SEQ ID NO: 296, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence differing therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In certain embodiments, the anti-APRIL antibody molecule comprises a VL comprising an amino acid sequence of SEQ ID NO: 286, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence differing therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In certain embodiments, the anti-APRIL antibody molecule comprises a VH comprising an amino acid sequence of SEQ ID NO: 296 and a VL comprising an amino acid sequence of SEQ ID NO: 286. In certain embodiments, the anti-APRIL antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region. In one embodiment, the anti-APRIL antibody molecule is sibeprenlimab.

[0252] In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg, or 8 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered once a month, once every two months, once every three months, or once every six months. In certain embodiments, 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 certain embodiments, 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 some embodiments, the anti-APRIL antibody molecule is administered intravenously or subcutaneously. In some embodiments, the anti-APRIL antibody molecule is administered intravenously. In some embodiments, the anti-APRIL antibody molecule is administered subcutaneously.

[0253] In an aspect, the 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; the subject is receiving a first anti-APRIL antibody molecule at a dose of at least 600 mg once every two weeks, and administration of the first anti-APRIL antibody is discontinued; a second anti-APRIL antibody molecule is administered no more than once a month; thereby treating IgA nephropathy.

[0254] 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or The VH comprises an HCDR1 having the amino acid sequence of SEQ ID NO: 17, an HCDR2 having the amino acid sequence of SEQ ID NO: 282, and an HCDR3 having the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 having the amino acid sequence of SEQ ID NO: 280, an LCDR2 having the amino acid sequence of SEQ ID NO: 285, and an LCDR3 having the amino acid sequence of SEQ ID NO: 16.

[0255] In one embodiment, upon identification of a subject receiving 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 discontinued and a second anti-APRIL antibody molecule is administered.

[0256] In certain embodiments, the method further comprises (a) identifying a subject receiving the first anti-APRIL antibody molecule at a dose of at least 600 mg once every two weeks; and (b) discontinuing administration of the first anti-APRIL antibody molecule.

[0257] In certain embodiments, the second anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO:296, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity 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 certain embodiments, the second anti-APRIL antibody molecule comprises a VL comprising the amino acid sequence of SEQ ID NO:286, or an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity 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 certain embodiments, 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. In some embodiments, the second anti-APRIL antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region. In some embodiments, the second anti-APRIL antibody molecule is cybeprenlimab.

[0258] In certain embodiments, the second anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg, or 8 mg / kg. In certain embodiments, the second anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In certain embodiments, the second anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In certain embodiments, the second anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In certain embodiments, 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 certain embodiments, 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 certain embodiments, 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 some embodiments, the second anti-APRIL antibody molecule is administered intravenously or subcutaneously. In some embodiments, the second anti-APRIL antibody molecule is administered intravenously. In some embodiments, the second anti-APRIL antibody molecule is administered subcutaneously.

[0259] In certain embodiments, 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.

[0260] In an aspect, the disclosure provides a method of treating IgA nephropathy, comprising administering to a subject in need thereof a second anti-APRIL antibody molecule at a dose of at least 600 mg once every two weeks; the subject is administered a first anti-APRIL antibody molecule, and administration of the first anti-APRIL antibody molecule is discontinued; thereby treating IgA nephropathy.

[0261] 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or The VH comprises an HCDR1 having the amino acid sequence of SEQ ID NO: 17, an HCDR2 having the amino acid sequence of SEQ ID NO: 282, and an HCDR3 having the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 having the amino acid sequence of SEQ ID NO: 280, an LCDR2 having the amino acid sequence of SEQ ID NO: 285, and an LCDR3 having the amino acid sequence of SEQ ID NO: 16.

[0262] In certain embodiments, the second anti-APRIL antibody molecule is administered depending on the identity of the subject receiving the first anti-APRIL antibody molecule.

[0263] In certain embodiments, the method further comprises (a) identifying a subject receiving the first anti-APRIL antibody molecule; and (b) discontinuing administration of the first anti-APRIL antibody molecule.

[0264] In certain embodiments, the first anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO:296, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity 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 certain embodiments, the first anti-APRIL antibody molecule comprises a VL comprising the amino acid sequence of SEQ ID NO:286, or an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity 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 certain embodiments, 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. In some embodiments, the first anti-APRIL antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region. In some embodiments, the first anti-APRIL antibody molecule is cybeprenlimab.

[0265] In certain embodiments, the first anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg, or 8 mg / kg. In certain embodiments, the first anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In certain embodiments, the first anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In certain embodiments, the first anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In certain embodiments, 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 certain embodiments, 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 certain embodiments, 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 some embodiments, the first anti-APRIL antibody molecule is administered intravenously or subcutaneously. In some embodiments, the first anti-APRIL antibody molecule is administered intravenously. In some embodiments, the first anti-APRIL antibody molecule is administered subcutaneously.

[0266] In certain embodiments, 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.

[0267] In an aspect, the disclosure provides a method of treating IgA nephropathy, comprising administering to a subject in need thereof an effective amount of an anti-APRIL antibody molecule, The subject is receiving (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 administration of (i) budesonide, (ii) atrasentan, (iii) dapagliflozin, or (iv) methylprednisolone is discontinued; the anti-APRIL antibody molecule is administered no more than once a month; thereby treating IgA nephropathy.

[0268] 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or The VH comprises an HCDR1 having the amino acid sequence of SEQ ID NO: 17, an HCDR2 having the amino acid sequence of SEQ ID NO: 282, and an HCDR3 having the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 having the amino acid sequence of SEQ ID NO: 280, an LCDR2 having the amino acid sequence of SEQ ID NO: 285, and an LCDR3 having the amino acid sequence of SEQ ID NO: 16.

[0269] In certain embodiments, the anti-APRIL antibody molecule is administered depending on the identity of a subject receiving (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).

[0270] In certain embodiments, the method further includes (a) identifying a subject receiving (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.

[0271] In certain embodiments, the anti-APRIL antibody molecule comprises a VH comprising an amino acid sequence of SEQ ID NO: 296, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence differing therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In certain embodiments, the anti-APRIL antibody molecule comprises a VL comprising an amino acid sequence of SEQ ID NO: 286, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence differing therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In certain embodiments, the anti-APRIL antibody molecule comprises a VH comprising an amino acid sequence of SEQ ID NO: 296 and a VL comprising an amino acid sequence of SEQ ID NO: 286. In certain embodiments, the anti-APRIL antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region. In one embodiment, the anti-APRIL antibody molecule is sibeprenlimab.

[0272] In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg, or 8 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered once a month, once every two months, once every three months, or once every six months. In certain embodiments, 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 certain embodiments, 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 some embodiments, the anti-APRIL antibody molecule is administered intravenously or subcutaneously. In some embodiments, the anti-APRIL antibody molecule is administered intravenously. In some embodiments, the anti-APRIL antibody molecule is administered subcutaneously.

[0273] In an aspect, the 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); the subject is receiving an anti-APRIL antibody molecule, and administration of the anti-APRIL antibody molecule is discontinued; thereby treating IgA nephropathy.

[0274] 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or The VH comprises an HCDR1 having the amino acid sequence of SEQ ID NO: 17, an HCDR2 having the amino acid sequence of SEQ ID NO: 282, and an HCDR3 having the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 having the amino acid sequence of SEQ ID NO: 280, an LCDR2 having the amino acid sequence of SEQ ID NO: 285, and an LCDR3 having the amino acid sequence of SEQ ID NO: 16.

[0275] In certain embodiments, (i) budesonide, (ii) atrasentan, (iii) dapagliflozin, or (iv) methylprednisolone are administered depending on the identity of the subject receiving the anti-APRIL antibody molecule.

[0276] In certain embodiments, the method further comprises (a) identifying the subject being administered the anti-APRIL antibody molecule; and (b) discontinuing administration of the anti-APRIL antibody molecule.

[0277] In certain embodiments, the anti-APRIL antibody molecule comprises a VH comprising an amino acid sequence of SEQ ID NO: 296, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence differing therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In certain embodiments, the anti-APRIL antibody molecule comprises a VL comprising an amino acid sequence of SEQ ID NO: 286, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence differing therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In certain embodiments, the anti-APRIL antibody molecule comprises a VH comprising an amino acid sequence of SEQ ID NO: 296 and a VL comprising an amino acid sequence of SEQ ID NO: 286. In certain embodiments, the anti-APRIL antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region. In one embodiment, the anti-APRIL antibody molecule is sibeprenlimab.

[0278] In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg, or 8 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 2 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 4 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered at a dose of 8 mg / kg. In certain embodiments, the anti-APRIL antibody molecule is administered once a month, once every two months, once every three months, or once every six months. In certain embodiments, 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 certain embodiments, 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 some embodiments, the anti-APRIL antibody molecule is administered intravenously or subcutaneously. In some embodiments, the anti-APRIL antibody molecule is administered intravenously. In some embodiments, the anti-APRIL antibody molecule is administered subcutaneously.

[0279] In an aspect, the disclosure provides a method of selecting a subject for a therapy comprising an anti-APRIL antibody molecule, the method comprising: (a) a subject, following administration of an anti-APRIL antibody molecule, (i) a 90% or greater reduction in the level of APRIL within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of APRIL; (ii) a 60% or greater reduction in the level of galactosyl IgA1 (Gd-IgA1) within 9 months of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of Gd-IgA; (iii) a 30% or greater reduction in 24-hour urinary protein creatinine ratio (uPCR) within 9 months of administration of the anti-APRIL antibody molecule compared to the subject's baseline uPCR; or (iv) determining whether the subject has one or more (e.g., two, three, or all) of the following: preserving (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; (b) selecting the subject based on a determination that the subject has one or more (e.g., two, three, or all) of (i), (ii), (iii), or (iv) after administration of the anti-APRIL antibody molecule; the anti-APRIL antibody molecule should be administered no more than once a month; The subject has or is at risk of having IgA nephropathy, Thereby, the method features a method for selecting a subject.

[0280] In certain 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or The VH comprises an HCDR1 having the amino acid sequence of SEQ ID NO: 17, an HCDR2 having the amino acid sequence of SEQ ID NO: 282, and an HCDR3 having the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 having the amino acid sequence of SEQ ID NO: 280, an LCDR2 having the amino acid sequence of SEQ ID NO: 285, and an LCDR3 having the amino acid sequence of SEQ ID NO: 16.

[0281] In an embodiment, the subject's baseline level of APRIL is the level of APRIL before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In an embodiment, the subject's baseline level of Gd-IgA is the level of Gd-IgA before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In an embodiment, the subject's baseline uPCR is uPCR before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In an embodiment, the subject's baseline eGFR is eGFR before administration of the anti-APRIL antibody molecule (e.g., before the first administration).

[0282] In one embodiment, determining whether a subject has one or more (e.g., two, three, or all) of (i), (ii), (iii), or (iv) after administration of an anti-APRIL antibody molecule is based, at least in part, on the testing described in Example 10.

[0283] In certain embodiments, the anti-APRIL antibody molecule comprises a VH comprising an amino acid sequence of SEQ ID NO: 296, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence differing therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In certain embodiments, the anti-APRIL antibody molecule comprises a VL comprising an amino acid sequence of SEQ ID NO: 286, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence differing therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In certain embodiments, the anti-APRIL antibody molecule comprises a VH comprising an amino acid sequence of SEQ ID NO: 296 and a VL comprising an amino acid sequence of SEQ ID NO: 286. In certain embodiments, the anti-APRIL antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region. In one embodiment, the anti-APRIL antibody molecule is sibeprenlimab.

[0284] In certain embodiments, the anti-APRIL antibody molecule should be administered at a dose of 2 mg / kg, 4 mg / kg, or 8 mg / kg. In certain embodiments, the anti-APRIL antibody molecule should be administered at a dose of 2 mg / kg. In certain embodiments, the anti-APRIL antibody molecule should be administered at a dose of 4 mg / kg. In certain embodiments, the anti-APRIL antibody molecule should be administered at a dose of 8 mg / kg. In certain embodiments, the anti-APRIL antibody molecule should be administered once a month, once every two months, once every three months, or once every six months. In certain embodiments, the anti-APRIL antibody molecule should be 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 certain embodiments, the anti-APRIL antibody molecule should 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 some embodiments, the anti-APRIL antibody molecule should be administered intravenously or subcutaneously. In some embodiments, the anti-APRIL antibody molecule should be administered intravenously. In some embodiments, the anti-APRIL antibody molecule should be administered subcutaneously. In some embodiments, the method further comprises administering the anti-APRIL antibody molecule to a subject.

[0285] In an aspect, the disclosure provides a method of selecting a therapy comprising an anti-APRIL antibody molecule for a subject, comprising: (a) a subject, following administration of an anti-APRIL antibody molecule, (i) a 90% or greater reduction in the level of APRIL within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of APRIL; (ii) a 60% or greater reduction in the level of galactosyl IgA1 (Gd-IgA1) within 9 months of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of Gd-IgA; (iii) a 30% or greater reduction in 24-hour urinary protein creatinine ratio (uPCR) within 9 months of administration of the anti-APRIL antibody molecule compared to the subject's baseline uPCR; or (iv) determining whether the subject has one or more (e.g., two, three, or all) of the following: preserving (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; (b) selecting a therapy comprising the anti-APRIL antibody molecule based on a determination that the subject has one or more (e.g., two, three, or all) of (i), (ii), (iii), or (iv) after administration of the anti-APRIL antibody molecule; the anti-APRIL antibody molecule is administered no more than once a month; The subject has or is at risk of having IgA nephropathy, This features a method for selecting a therapy.

[0286] In certain 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or The VH comprises an HCDR1 having the amino acid sequence of SEQ ID NO: 17, an HCDR2 having the amino acid sequence of SEQ ID NO: 282, and an HCDR3 having the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 having the amino acid sequence of SEQ ID NO: 280, an LCDR2 having the amino acid sequence of SEQ ID NO: 285, and an LCDR3 having the amino acid sequence of SEQ ID NO: 16.

[0287] In an embodiment, the subject's baseline level of APRIL is the level of APRIL before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In an embodiment, the subject's baseline level of Gd-IgA is the level of Gd-IgA before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In an embodiment, the subject's baseline uPCR is uPCR before administration of the anti-APRIL antibody molecule (e.g., before the first administration). In an embodiment, the subject's baseline eGFR is eGFR before administration of the anti-APRIL antibody molecule (e.g., before the first administration).

[0288] In one embodiment, determining whether a subject has one or more (e.g., two, three, or all) of (i), (ii), (iii), or (iv) after administration of an anti-APRIL antibody molecule is based, at least in part, on the testing described in Example 10.

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

[0290] In certain embodiments, the anti-APRIL antibody molecule should be administered at a dose of 2 mg / kg, 4 mg / kg, or 8 mg / kg. In certain embodiments, the anti-APRIL antibody molecule should be administered at a dose of 2 mg / kg. In certain embodiments, the anti-APRIL antibody molecule should be administered at a dose of 4 mg / kg. In certain embodiments, the anti-APRIL antibody molecule should be administered at a dose of 8 mg / kg. In certain embodiments, the anti-APRIL antibody molecule should be administered once a month, once every two months, once every three months, or once every six months. In certain embodiments, the anti-APRIL antibody molecule should be 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 certain embodiments, the anti-APRIL antibody molecule should 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 some embodiments, the anti-APRIL antibody molecule should be administered intravenously or subcutaneously. In some embodiments, the anti-APRIL antibody molecule should be administered intravenously. In some embodiments, the anti-APRIL antibody molecule should be administered subcutaneously. In some embodiments, the method further comprises administering the anti-APRIL antibody molecule to a subject.

[0291] Enumerated embodiments 1. A method for treating a disorder, comprising: administering to a subject in need thereof an anti-APRIL antibody molecule as described herein; the antibody molecule is administered at a dose that reduces or is likely to reduce levels of abnormally 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%); thereby treating a disorder.

[0292] 2. A method for treating a disorder, comprising: administering to a subject in need thereof an anti-APRIL antibody molecule as described herein; 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%); thereby treating a disorder.

[0293] 3. A method for treating a disorder, comprising: administering to a subject in need thereof an anti-APRIL antibody molecule as described herein; the antibody molecule is administered at a dosage (e.g., dose and frequency) that reduces or is likely to reduce levels 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%); thereby treating a disorder.

[0294] 4. A method for treating a disorder, comprising: selecting a dose or dosage (e.g., dose and frequency) of an anti-APRIL antibody molecule described herein, where administration of the antibody molecule at that dose or dosage will reduce or is likely to reduce levels 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 administering to a subject an antibody molecule at a selected dose or dosage; thereby treating a disorder.

[0295] 5. A method for treating a disorder, comprising: in response to a determination that administration of an anti-APRIL antibody molecule described herein will reduce 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 an anti-APRIL antibody molecule to the subject; thereby treating a disorder.

[0296] 6. A method for treating a disorder, comprising: determining whether administration of an anti-APRIL antibody molecule described herein will reduce 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%); if the antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40%, initiating, continuing or maintaining administration of the antibody molecule; Optionally, if the antibody molecule does not reduce or is not likely to reduce the level of ag IgA by at least 40%, then administration of the antibody molecule is terminated, discontinued or altered, and / or a different therapeutic agent or treatment modality is administered.

[0297] 7. A method for treating a disorder, comprising: determining whether administration of an anti-APRIL antibody molecule described herein at a dose or dosage will reduce 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%); if the antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at that dose or dosage, then initiating, continuing, or maintaining administration of the antibody molecule at that dose or dosage; and optionally terminating, discontinuing or modifying administration of the antibody molecule at that dose or dosage if the antibody molecule does not reduce or is not likely to reduce the level of ag IgA by at least 40% at that dose or dosage.

[0298] 8. A method for treating a disorder, comprising: determining whether administration of a therapeutic agent or treatment modality other than an anti-APRIL antibody molecule described herein will reduce 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%); A method comprising the step of administering to a subject an anti-APRIL antibody molecule described herein, unless the therapeutic agent or treatment modality does not reduce or is likely to reduce the level of ag IgA by at least 40%.

[0299] 9. A method for reducing the level of ag IgA in a subject, comprising: administering to a subject in need thereof an anti-APRIL antibody molecule as described herein at a dose or dosage that reduces or is likely to reduce levels of ag IgA in the subject, e.g., by at least 40% (e.g., by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%); thereby reducing the level of ag IgA.

[0300] 10. A method for selecting an anti-APRIL antibody molecule for treating a disorder, comprising: determining whether administration of an anti-APRIL antibody molecule described herein will reduce 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%); This method selects anti-APRIL antibody molecules.

[0301] 11. A method for selecting a dose or dosage (e.g., dose and frequency) of an anti-APRIL antibody molecule for treating a disorder, comprising: determining whether administration of an anti-APRIL antibody molecule described herein at a dose or dosage will reduce 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%); This method allows for the selection of a dose or dosage.

[0302] 12. A method for selecting a subject for treating a disorder, comprising: determining whether administration of an anti-APRIL antibody molecule described herein will reduce 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%); This allows you to select the target, Optionally, if the antibody molecule does not reduce or is likely to reduce the level of ag IgA by at least 40%, then administration of the antibody molecule is terminated, discontinued or altered, or a different therapeutic agent or treatment modality is administered.

[0303] 13. The method of any of the preceding claims, wherein the ag IgA comprises or is ag IgA1.

[0304] 14. The method of any of embodiments 1 to 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%) over a given period of time, such as at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months.

[0305] 15. The method of any of embodiments 1 to 14, 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 the antibody molecule is administered.

[0306] 16. The method of any of embodiments 1 to 15, 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 the antibody molecule is administered.

[0307] 17. The method of any of embodiments 1 to 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 the antibody molecule is administered.

[0308] 18. The method of any of embodiments 1 to 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 the antibody molecule is administered.

[0309] 19. The method of any of embodiments 1 to 18, wherein the level of ag IgA is reduced by at least 50%.

[0310] 20. The method of any of embodiments 1 to 19, wherein the level of ag IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

[0311] 21. The method of any of embodiments 1 to 20, wherein the antibody molecule is administered as a single dose.

[0312] 22. The method of any of embodiments 1 to 20, wherein the antibody molecule is administered as repeated doses.

[0313] 23. The method of any preceding embodiment, wherein the antibody molecule is administered subcutaneously.

[0314] 24. The method of any preceding embodiment, wherein the antibody molecule is administered intravenously.

[0315] 25. The method of any of the preceding embodiments, wherein the disorder is an APRIL-associated disorder.

[0316] 26. The method of any of embodiments 1-25, wherein the disorder is associated with abnormal levels of total IgA.

[0317] 27. The method of any of the preceding embodiments, wherein the disorder is an ag IgA-associated disorder.

[0318] 28. The method of any of the preceding embodiments, wherein the disorder is IgA nephropathy (IgAN).

[0319] 29. The method of embodiment 28, wherein the IgAN is familial IgAN.

[0320] 30. The method of embodiment 28, wherein the IgAN is adult IgAN.

[0321] 31. The method of embodiment 28, wherein the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0322] 32. The method of any of embodiments 1-27, wherein the disorder is chronic kidney disease (CKD) or a disorder associated with CKD.

[0323] 33. The method of embodiment 32, wherein the CKD is advanced CKD, for example with an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0324] 34. The method of any of embodiments 1-27, wherein the disorder is Henoch-Schönlein purpura (HSP).

[0325] 35. The method of any of embodiments 1-27, wherein the disorder is cutaneous vasculitis or IgA vasculitis.

[0326] 36. The method of any of embodiments 1-27, wherein the disorder is IgA dermatitis, such as IgA bullous disease.

[0327] 37. The method of any of embodiments 1-27, wherein the disorder is Waldenström's Macroglobulinemia (WM).

[0328] 38. The method of any of embodiments 1-27, wherein the disorder is lupus nephritis.

[0329] 39. The method of any preceding embodiment, wherein the subject is a human.

[0330] 40. The method of any of embodiments 1 to 39, wherein the subject has or has been identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, e.g. a subject not having the disorder, e.g. a healthy or normal subject.

[0331] 41. The method of any of embodiments 1 to 40, wherein the subject has or has been identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, e.g. a subject without the disorder, e.g. a healthy or normal subject.

[0332] 42. The method of any of embodiments 1 to 41, wherein the subject has received or is receiving a different therapeutic agent or therapeutic modality for treating the disorder.

[0333] 43. The method of any of embodiments 1 to 41, wherein the subject has not received or is not receiving a different therapeutic agent or therapeutic modality for treating the disorder.

[0334] 44. The method of any of embodiments 1 to 43, wherein the subject has received, is receiving, or is about to receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or within 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule.

[0335] 45. The method of any of embodiments 1 to 43, wherein the subject is in need of, or has been identified as in need of, receiving the vaccine within, e.g., 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.

[0336] 46. ​​The method of embodiment 44 or 45, wherein the subject receives a vaccine prior to, simultaneously with, or after administration of the antibody molecule.

[0337] 47. The method of any of embodiments 44 to 46, wherein administration of the antibody molecule reduces the subject's ability to have 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%.

[0338] 48. The method of any of embodiments 44 to 47, wherein administration of the antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine.

[0339] 49. The method of any of embodiments 44 to 48, 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.

[0340] 50. The method of any of embodiments 44-49, wherein the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®).

[0341] 51. The method of embodiment 50, wherein the subject has or maintains effective (e.g. protective) levels (e.g. greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria anti-toxoid IgG, 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.

[0342] 52. The method of any of embodiments 1 to 51, wherein the subject has or has been identified as having a genomic susceptibility locus for the disorder, such as IgA nephropathy.

[0343] 53. The method of any of embodiments 1 to 52, further comprising a step of determining whether the subject has a genomic susceptibility locus for the disorder, e.g., IgA nephropathy.

[0344] 54. Antibody molecule is an 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, 3 54. The method of any of the preceding claims, comprising an HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of any of: 327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237.

[0345] 55. The antibody molecule is an 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, 55. The method of any of the preceding claims, comprising a VH and VL of any of 2419-1406, 2922, 3327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237.

[0346] 56. The method of any preceding embodiment, wherein the level of ag IgA is determined in a sample from the subject.

[0347] 57. The method of any of the preceding embodiments, further comprising determining the level of ag IgA in a sample from the subject.

[0348] 58. The method of any of the preceding embodiments, further comprising determining the level of total IgA in the sample.

[0349] 59. The method of any of the preceding embodiments, further comprising determining the level of IgM and / or IgG in the sample.

[0350] 60. The method of any of the preceding claims, further comprising obtaining a sample from a subject.

[0351] 61. The method of embodiment 60, wherein the sample is a blood or serum sample.

[0352] 62. The method of any of embodiments 1-61, further comprising administering to the subject a second therapeutic agent or treatment modality.

[0353] 63. The method of embodiment 62, wherein the second therapeutic agent or therapeutic modality is a small molecule.

[0354] 64. The method of embodiment 62, wherein the second therapeutic agent or therapeutic modality is an antibody molecule.

[0355] 65. A method for treating IgA nephropathy, comprising: 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); 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; thereby treating IgA nephropathy.

[0356] 66. The method of embodiment 65, further comprising the step of administering a vaccine to the subject prior to, simultaneously with, or after administration of the antibody molecule.

[0357] 67. A method of vaccinating a subject, comprising: administering to a subject an effective amount of a vaccine (e.g., a vaccine described herein); 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; whereby the subject is vaccinated.

[0358] 68. The method of embodiment 67, further comprising the step of administering an antibody molecule to the subject prior to, simultaneously with, or after administration of the vaccine.

[0359] 69. The method of any of embodiments 44 to 68, wherein the vaccine is administered intramuscularly.

[0360] 70. A composition for use in treating IgA nephropathy in a subject, the composition comprising 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; A composition, wherein the subject has received or is about to 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.

[0361] 71. The composition for use according to embodiment 70, further comprising administering to the subject a vaccine prior to, simultaneously with, or after administration of the antibody molecule.

[0362] 72. A composition for use in vaccinating a subject, comprising an effective amount of a vaccine (e.g., a vaccine described herein), A composition wherein the subject has received or is about to 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, and the subject has received or is about to 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.

[0363] 73. The composition for use according to embodiment 72, wherein the subject is administered the antibody molecule prior to, simultaneously with, or after administration of the vaccine.

[0364] 74. A composition for use in treating a disorder in a subject, comprising: comprising an anti-APRIL antibody molecule as described herein in 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, A composition, wherein the dosage reduces or is likely to reduce levels of abnormally glycosylated IgA (ag IgA) in a subject by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%).

[0365] 75. A composition for use in treating a disorder in a subject, comprising an anti-APRIL antibody molecule as described herein in 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; A composition, wherein the dosage reduces the level of ag IgA in a subject by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%).

[0366] 76. A composition for use in treating a disorder in a subject, comprising an anti-APRIL antibody molecule as described herein in a dosage (e.g., dose and frequency) that reduces or is likely to reduce levels 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%), A composition 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.

[0367] 77. A composition for use in treating a disorder in a subject, the composition comprising an anti-APRIL antibody molecule as described herein administered to a 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; The composition is formulated and administered if administration of a therapeutic agent or treatment modality other than the anti-APRIL antibody molecules described herein reduces or is likely to reduce the level of ag IgA in a subject by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%).

[0368] 78. A composition for use in reducing the level of ag IgA in a subject, comprising an anti-APRIL antibody molecule as described herein in 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%) to a subject in need thereof, A composition 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.

[0369] 79. A method for treating IgA nephropathy, comprising: 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; 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; thereby treating IgA nephropathy.

[0370] 80. The method of embodiment 79, further comprising the step of administering a vaccine to the subject prior to, simultaneously with, or after administration of the antibody molecule.

[0371] 81. A method of vaccinating a subject, comprising: administering to a subject an effective amount of a vaccine (e.g., a vaccine described herein); the subject has received or is about to 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, and the subject has received or is about to receive an 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; whereby the subject is vaccinated.

[0372] 82. The method of embodiment 81, further comprising the step of administering an antibody molecule to the subject prior to, simultaneously with, or after administration of the vaccine.

[0373] 83. A method for treating a disorder, comprising: administering to a subject in need thereof an anti-APRIL antibody molecule as described herein; 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; the dosage administered to the subject reduces or is likely to reduce the level of abnormally 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%); thereby treating a disorder.

[0374] 84. A method for treating a disorder, comprising: administering to a subject in need thereof an anti-APRIL antibody molecule as 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; 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%); thereby treating a disorder.

[0375] 85. A method for treating a disorder, comprising: administering to a subject in need thereof an anti-APRIL antibody molecule as described herein; the antibody molecule is administered at a dosage (e.g., dose and frequency) that reduces or is likely to reduce levels 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%); the dosage is a fixed 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 about 200 mg, 400 mg, 600 mg, or 800 mg; thereby treating a disorder.

[0376] 86. A method for treating a disorder, comprising: selecting a dose or dosage (e.g., dose and frequency) of an anti-APRIL antibody molecule described herein; the dose or dosage is a fixed 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 about 200 mg, 400 mg, 600 mg, or 800 mg; administration of the antibody molecule at that dose or dosage reduces or is likely to reduce levels 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 administering to a subject an antibody molecule at a selected dose or dosage; thereby treating a disorder.

[0377] 87. A method for treating a disorder, comprising: in response to a determination that administration of an anti-APRIL antibody molecule described herein will reduce 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 an 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; thereby treating a disorder.

[0378] 88. A method for treating a disorder, comprising: determining whether administration of an anti-APRIL antibody molecule described herein will reduce 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%); if the antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40%, 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; Optionally, if the antibody molecule does not reduce or is not likely to reduce the level of ag IgA by at least 40%, then administration of the antibody molecule is terminated, discontinued or altered, and / or a different therapeutic agent or treatment modality is administered.

[0379] 89. A method for treating a disorder, comprising: determining whether administration of an anti-APRIL antibody molecule described herein at a dose or dosage will reduce 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%); if the antibody molecule reduces or is likely to reduce the level of ag IgA by at least 40% at that dose or dosage, then initiating, continuing, or maintaining administration of the antibody molecule at that dose or dosage; the dose or dosage is a fixed 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 about 200 mg, 400 mg, 600 mg, or 800 mg; and optionally terminating, discontinuing or modifying administration of the antibody molecule at that dose or dosage if the antibody molecule does not reduce or is not likely to reduce the level of ag IgA by at least 40% at that dose or dosage.

[0380] 90. A method for treating a disorder, comprising: determining whether administration of a therapeutic agent or treatment modality other than an anti-APRIL antibody molecule described herein will reduce 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%); A method comprising administering to a subject 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, unless the therapeutic agent or treatment modality does not reduce or is likely to reduce the level of ag IgA by at least 40%.

[0381] 91. A method for reducing the level of ag IgA in a subject, comprising: administering to a subject in need thereof an anti-APRIL antibody molecule as 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%); the dose or dosage is a fixed 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 about 200 mg, 400 mg, 600 mg, or 800 mg; thereby reducing the level of ag IgA.

[0382] 92. A method for selecting an anti-APRIL antibody molecule for treating a disorder, comprising: 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 will reduce or are likely to reduce levels of ag IgA by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%) in a subject in need thereof; This method selects anti-APRIL antibody molecules.

[0383] 93. A method for selecting a dose or dosage (e.g., dose and frequency) of an anti-APRIL antibody molecule for treating a disorder, comprising: determining whether administration of an anti-APRIL antibody molecule described herein at a dose or dosage will reduce 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%); the dose or dosage is a fixed 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 about 200 mg, 400 mg, 600 mg, or 800 mg; This method allows for the selection of a dose or dosage.

[0384] 94. A method for selecting a subject for treating a disorder, comprising: 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 will reduce or are likely to reduce levels of ag IgA by at least 40% (e.g., at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%) in a subject in need thereof; This allows you to select the target, Optionally, if the antibody molecule does not reduce or is likely to reduce the level of ag IgA by at least 40%, then administration of the antibody molecule is terminated, discontinued or altered, or a different therapeutic agent or treatment modality is administered.

[0385] 95. The method of any of embodiments 79 to 94, wherein the ag IgA comprises or is ag IgA1.

[0386] 96. The method of any of embodiments 79 to 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%) over a given period of time, e.g., at least 1, 2, 3, or 4 weeks, or at least 1, 2, or 3 months.

[0387] 97. The method of any of embodiments 79 to 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 the antibody molecule is administered.

[0388] 98. The method of any of embodiments 79 to 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 the antibody molecule is administered.

[0389] 99. The method of any of embodiments 79 to 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 the antibody molecule is administered.

[0390] 100. The method of any of embodiments 79 to 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 the antibody molecule is administered.

[0391] 101. The method of any of embodiments 79 to 100, wherein the level of ag IgA is reduced by at least 50%.

[0392] 102. The method of any of embodiments 79 to 101, wherein the level of ag IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

[0393] 103. The method of any of embodiments 79-102, wherein the antibody molecule is administered as a single dose, for example for 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.

[0394] 104. The method of any of embodiments 79 to 102, wherein the antibody molecule is administered as repeated doses.

[0395] 105. The method of any of embodiments 79 to 104, wherein the antibody molecule is administered subcutaneously.

[0396] 106. The method of any of embodiments 79 to 104, wherein the antibody molecule is administered intravenously.

[0397] 107. The method of any of embodiments 79-106, wherein the disorder is an APRIL-associated disorder.

[0398] 108. The method of any of embodiments 79-107, wherein the disorder is associated with abnormal levels of total IgA.

[0399] 109. The method of any of embodiments 79-108, wherein the disorder is an ag IgA-associated disorder.

[0400] 110. The method of any of embodiments 79-109, wherein the disorder is IgA nephropathy (IgAN).

[0401] 111. The method of embodiment 110, wherein the IgAN is familial IgAN.

[0402] 112. The method of embodiment 110, wherein the IgAN is adult IgAN.

[0403] 113. The method of embodiment 110, wherein the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0404] 114. The method according to any of embodiments 79 to 108, wherein the disorder is chronic kidney disease (CKD) or a disorder associated with CKD.

[0405] 115. The method according to embodiment 114, wherein the CKD is advanced CKD, for example with an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0406] 116. The method of any of embodiments 79-108, wherein the disorder is Henoch-Schönlein purpura (HSP).

[0407] 117. The method according to any of embodiments 79-108, wherein the disorder is cutaneous vasculitis or IgA vasculitis.

[0408] 118. The method of any of embodiments 79-108, wherein the disorder is IgA dermatitis, e.g. IgA bullous disease.

[0409] 119. The method of any of embodiments 79-108, wherein the disorder is Waldenström's Macroglobulinemia (WM).

[0410] 120. The method of any of embodiments 79-108, wherein the disorder is lupus nephritis.

[0411] 121. The method of any of embodiments 79 to 120, wherein the subject is a human.

[0412] 122. The method of any of embodiments 79 to 121, wherein the subject has or has been identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, e.g. a subject not having the disorder, e.g. a healthy or normal subject.

[0413] 123. The method of any of embodiments 79 to 122, wherein the subject has or has been identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, e.g. a subject without the disorder, e.g. a healthy or normal subject.

[0414] 124. The method of any of embodiments 79 to 123, wherein the subject has received or is receiving a different therapeutic agent or therapeutic modality for treating the disorder.

[0415] 125. The method of any of embodiments 79 to 123, wherein the subject has not received or is not receiving a different therapeutic agent or therapeutic modality for treating the disorder.

[0416] 126. The method of any of embodiments 79 to 125, wherein the subject has received, is receiving, or is about to receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or within 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule.

[0417] 127. The method of any of embodiments 79 to 125, wherein the subject is in need of, or has been identified as in need of, receiving a vaccine within, for example, 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.

[0418] 128. The method of embodiment 126 or 127, wherein the subject receives a vaccine prior to, simultaneously with, or after administration of the antibody molecule.

[0419] 129. The method of any of embodiments 126 to 128, wherein administration of the antibody molecule reduces the subject's ability to have 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%.

[0420] 130. The method of any of embodiments 126 to 129, wherein administration of the antibody molecule does not reduce or does not substantially reduce the subject's ability to have an effective antigen-specific serum IgG and / or IgA response to the vaccine.

[0421] 131. The method of any of embodiments 126 to 130, 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.

[0422] 132. The method of any of embodiments 126-131, wherein the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®).

[0423] 133. The method of embodiment 132, wherein the subject has or maintains an effective (e.g., protective) level (e.g., greater than or equal to 0.1 IU / mL in the blood) of tetanus and / or diphtheria antitoxoid IgG, 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.

[0424] 134. The method of any of embodiments 79-133, wherein the subject has or has been identified as having a genomic susceptibility locus for the disorder, such as IgA nephropathy.

[0425] 135. The method of any of embodiments 79 to 134, further comprising determining whether the subject has a genomic susceptibility locus for the disorder, e.g., IgA nephropathy.

[0426] 136. Antibody molecule is an 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, 3 The method of any of embodiments 79 to 135, comprising an HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of any of 327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237.

[0427] 137. Antibody molecule is an 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, 2 The method of any of embodiments 79-136, comprising a VH and VL of any of 419-1406, 2922, 3327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237.

[0428] 138. The method of any of embodiments 79 to 137, wherein the level of ag IgA is determined in a sample from the subject.

[0429] 139. The method of any of embodiments 79 to 138, further comprising determining the level of ag IgA in a sample from the subject.

[0430] 140. The method of any of embodiments 79 to 139, further comprising determining the level of total IgA in the sample.

[0431] 141. The method of any of embodiments 79 to 140, further comprising determining the level of IgM and / or IgG in the sample.

[0432] 142. The method of any of embodiments 79 to 141, further comprising obtaining a sample from a subject.

[0433] 143. The method of embodiment 142, wherein the sample is a blood or serum sample.

[0434] 144. The method of any of embodiments 79 to 143, further comprising administering to the subject a second therapeutic agent or treatment modality.

[0435] 145. The method of embodiment 144, wherein the second therapeutic agent or therapeutic modality is a small molecule.

[0436] 146. The method of embodiment 144, wherein the second therapeutic agent or therapeutic modality is an antibody molecule.

[0437] 147. The method or composition for use of any of the preceding embodiments, wherein the subject is administered the anti-APRIL antibody molecule at a concentration of about 100, 150, 175, 180, 190, 200, 210, 220, 225, 230, 240, 250, or 300 mg / mL.

[0438] 148. The method or composition for use of any of the preceding embodiments, wherein the subject is administered the anti-APRIL antibody molecule at a concentration of about 200 mg / mL.

[0439] 149. The method or composition for use according to any of the preceding embodiments, wherein the subject is administered a fixed dosage of about 200, 250, 300, 450, 400, 450, 500, 550, 600, 650, 700, 750, or 800 mg of the anti-APRIL antibody molecule.

[0440] 150. A method or composition for use according to any of the preceding embodiments, wherein the subject is administered the anti-APRIL antibody molecule in a fixed dosage of about 200 mg (e.g. in a volume of about 1 mL).

[0441] 151. The method or composition for use according to any of the preceding embodiments, wherein the subject is administered the anti-APRIL antibody molecule in a fixed dosage of about 400 mg (e.g. in a total volume of about 2 mL, e.g. as two doses in a volume of 1 mL or as a single dose in a volume of 2 mL).

[0442] 152. A method or composition for use according to any of the preceding embodiments, wherein the subject is administered a fixed dosage of at least 200 mg of the anti-APRIL antibody molecule.

[0443] 153. A method or composition for use according to any of the preceding embodiments, wherein the subject is administered a fixed dosage of 800 mg or less of the anti-APRIL antibody molecule.

[0444] 154. The method or composition for use according to any of the preceding embodiments, wherein the subject is administered the anti-APRIL antibody molecule in a fixed dosage of about 600 mg (e.g. in a total volume of about 3 mL, e.g. as one administration in a volume of 2 mL and one administration in a volume of 1 mL).

[0445] 155. The method or composition for use of any of the preceding embodiments, wherein the subject is administered a single dose of the anti-APRIL antibody molecule.

[0446] 156. The method or composition for use of any of the preceding embodiments, wherein the subject is administered one or more additional dosages 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 initial administration).

[0447] 157. A method or composition for use according to any of the preceding embodiments, wherein the subject is administered the anti-APRIL antibody molecule subcutaneously.

[0448] 158. A method or composition for use according to any of the preceding embodiments, wherein the subject is administered the anti-APRIL antibody molecule intravenously.

[0449] 159. A method or composition for use according to any of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered as a liquid.

[0450] 160. An anti-APRIL antibody molecule or a pharmaceutical composition comprising an anti-APRIL antibody molecule for use in a method for treating a disorder in a human subject, comprising: 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; administration reduces the level of abnormally 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%; 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, the antibody molecule or pharmaceutical composition, wherein the disorder is IgA nephropathy.

[0451] 161. An anti-APRIL antibody molecule or a pharmaceutical composition comprising an anti-APRIL antibody molecule for use in a method for reducing the level of ag IgA in a human subject, comprising: 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; administration reduces 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%; 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, the antibody molecule or pharmaceutical composition, wherein the subject has or is at risk of having a disorder, such as IgA nephropathy.

[0452] 162. An anti-APRIL antibody molecule or a pharmaceutical composition comprising an anti-APRIL antibody molecule for use in a method for treating a disorder in a human subject, comprising: The method comprises the step of selecting a dose or dosage of an antibody molecule; administration of the antibody molecule at a selected dose or dosage reduces or is likely to reduce levels of ag IgA in a subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%; 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, 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; Optionally, the antibody molecule or pharmaceutical composition, wherein the disorder is IgA nephropathy.

[0453] 163. An anti-APRIL antibody molecule or a pharmaceutical composition comprising an anti-APRIL antibody molecule for use in a method for treating a disorder in a human subject, comprising: in response to a determination that administration of the antibody molecule will reduce 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%, 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; 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, the antibody molecule or pharmaceutical composition, wherein the disorder is IgA nephropathy.

[0454] 164. An anti-APRIL antibody molecule or a pharmaceutical composition comprising an anti-APRIL antibody molecule for use in a method for treating a disorder in a human subject, comprising: the method comprising determining whether administration of an 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%; if the antibody molecule reduces or is likely to reduce levels 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; 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, 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; Optionally, the disorder is IgA nephropathy, Optionally, terminate, discontinue or modify administration of the antibody molecule and / or administer a different therapeutic agent or treatment modality if the antibody molecule or pharmaceutical composition does not reduce or is not likely to reduce levels of ag IgA by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%.

[0455] 165. An anti-APRIL antibody molecule or a pharmaceutical composition comprising an anti-APRIL antibody molecule for use in a method for treating a disorder in a human subject, comprising: The method includes determining whether administration of a therapeutic agent or treatment modality other than an antibody molecule will reduce 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%; administering to the subject an antibody molecule 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, unless the therapeutic agent or treatment modality does not reduce or is likely to reduce levels of ag IgA by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%, 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, the antibody molecule or pharmaceutical composition, wherein the disorder is IgA nephropathy.

[0456] 166. An anti-APRIL antibody molecule or a pharmaceutical composition comprising an anti-APRIL antibody molecule for use in a method for treating a disorder in a human subject, comprising: 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; 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, and optionally the vaccine includes a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®); 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, the disorder is IgA nephropathy, Optionally, the antibody molecule or pharmaceutical composition, wherein administration of the antibody molecule at a selected dose or dosage reduces or is likely to reduce levels of ag IgA in a subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%.

[0457] 167. A method for treating a disorder, comprising: administering an 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; administration reduces the level of abnormally 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%; 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); Optionally, the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, the disorder is IgA nephropathy, thereby treating a disorder.

[0458] 168.A method for reducing levels of IgA, comprising: administering an anti-APRIL antibody molecule to a human subject in need thereof; 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; administration reduces 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%; 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, the subject has or is at risk of having a disorder, e.g., IgA nephropathy; thereby reducing the level of ag IgA.

[0459] 169. A method for treating a disorder, comprising: selecting a dose or dosage of an anti-APRIL antibody molecule; administration of the antibody molecule at a selected dose or dosage reduces or is likely to reduce levels of ag IgA in a subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%; 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, 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; Optionally, the subject has or is at risk of having IgA nephropathy; thereby treating a disorder.

[0460] 170. A method for treating a disorder, comprising: in response to a determination that administration of the antibody molecule will reduce 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%, administering an 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; 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, the disorder is IgA nephropathy, thereby treating a disorder.

[0461] 171. A method for treating a disorder, comprising: determining whether administration of the anti-APRIL antibody molecule will reduce 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%; if the antibody molecule reduces or is likely to reduce levels 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; 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, 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; optionally, terminating, discontinuing or modifying administration of the antibody molecule and / or administering a different therapeutic agent or treatment modality if the antibody molecule does not reduce or is not likely 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%; Optionally, the disorder is IgA nephropathy, thereby treating a disorder.

[0462] 172. A method for treating a disorder, comprising: determining whether administration of a therapeutic agent or treatment modality other than an anti-APRIL antibody molecule will reduce 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%; administering to a human subject an antibody molecule 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, unless the therapeutic agent or treatment modality does not reduce or is likely to reduce levels of ag IgA by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%, 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, the disorder is IgA nephropathy, thereby treating a disorder.

[0463] 173. A method for treating a disorder, comprising: administering an 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; 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, and optionally the vaccine includes a tetanus toxoid, a diphtheria toxoid, or both (e.g., TENIVAC®); 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, the disorder is IgA nephropathy, optionally, administration of the antibody molecule at a selected dose or dosage reduces or is likely to reduce levels of ag IgA in the subject by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%; thereby treating a disorder.

[0464] 174. A method for selecting an anti-APRIL antibody molecule for treating a disorder, comprising: determining whether administration of the antibody molecule at a dose or dosage will reduce or is likely to reduce levels 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%; 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 a fixed dose of about 200 mg, 400 mg, 600 mg, or 800 mg; 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, the disorder is IgA nephropathy, This method selects antibody molecules.

[0465] 175. A method for selecting a dose or dosage of an anti-APRIL antibody molecule for treating a disorder, comprising: determining whether administration of the antibody molecule at a dose or dosage will reduce or is likely to reduce levels 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%; Optionally, 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; 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, the disorder is IgA nephropathy, This method allows for the selection of a dose or dosage.

[0466] 176. A method for selecting a human subject for treating a disorder, comprising: determining whether administration of an 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 will reduce or are 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%; 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, the disorder is IgA nephropathy, This method selects the target.

[0467] 177. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 176, wherein the ag IgA comprises or is ag IgA1.

[0468] 178.ag Antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 177, wherein the level of IgA is reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% over a defined period of time, e.g. 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.

[0469] 179. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 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 the antibody molecule is administered.

[0470] 180. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 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% at about 8 weeks after the antibody molecule is administered.

[0471] 181. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 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 the antibody molecule is administered.

[0472] 182. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 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% at about 16 weeks after the antibody molecule is administered.

[0473] 183.An antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 182, in which the level of ag IgA is reduced by at least 50%.

[0474] 184.Ag The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 183, wherein the level of IgA is reduced by at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

[0475] 185. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 184, for example for 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.

[0476] 186. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 185, wherein the antibody molecule is administered as repeated doses, e.g., over a period of at least 3, 6, 9, 12, 15, 18, 24, 30, or 36 months, and, optionally, the subject is administered one or more additional dosages 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).

[0477] 187. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 186, wherein the antibody molecule is administered subcutaneously.

[0478] 188. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 186, wherein the antibody molecule is administered intravenously.

[0479] 189. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 188, wherein the disorder is an APRIL-associated disorder.

[0480] 190. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 189, wherein the disorder is associated with abnormal levels of total IgA.

[0481] 191. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 190, wherein the disorder is an ag IgA-associated disorder.

[0482] 192. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 191, wherein the disorder is IgA nephropathy (IgAN).

[0483] 193. The antibody molecule, pharmaceutical composition, method for use according to embodiment 192, wherein the IgAN is familial IgAN.

[0484] 194. The antibody molecule, pharmaceutical composition, method for use according to embodiment 192, wherein the IgAN is adult IgAN.

[0485] 195. The antibody molecule, pharmaceutical composition, method for use according to embodiment 192, wherein the IgAN is post-transplant IgAN, pediatric IgAN, or crescentic IgAN.

[0486] 196. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 191, wherein the disorder is chronic kidney disease (CKD) or a disorder associated with CKD.

[0487] 197. The antibody molecule, pharmaceutical composition, method for use according to embodiment 196, wherein the CKD is advanced CKD, for example with an estimated glomerular filtration rate (eGFR) equal to or greater than about 30 or about 45.

[0488] 198. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 191, wherein the disorder is Henoch-Schönlein purpura (HSP).

[0489] 199. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 191, wherein the disorder is cutaneous vasculitis or IgA vasculitis.

[0490] 200. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 191, wherein the disorder is IgA dermatitis, such as IgA bullous disease.

[0491] 201. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 191, wherein the disorder is Waldenström's Macroglobulinemia (WM).

[0492] 202. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 191, wherein the disorder is lupus nephritis.

[0493] 203. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 202, wherein the subject is a human patient.

[0494] 204. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 203, wherein the subject has or has been identified as having a level of ag IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of ag IgA in a reference subject, e.g. a subject not having the disorder, e.g. a healthy or normal subject.

[0495] 205. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 204, wherein the subject has or is identified as having a level of total IgA that is at least 1, 1.5, 2, 2.5, 3.5, 4, 4.5, or 5 times higher than the level of total IgA in a reference subject, e.g. a subject not having the disorder, e.g. a healthy or normal subject.

[0496] 206. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 205, wherein the subject has received or is receiving a different therapeutic agent or therapeutic modality for treating the disorder.

[0497] 207. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 206, wherein the subject has not received or is not receiving a different therapeutic agent or therapeutic modality for treating the disorder.

[0498] 208. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 207, wherein the subject has received, has received, or is about to receive a vaccine, e.g., within 1, 2, 3, 4, 5, or 6 days, or within 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 weeks of administration of the antibody molecule.

[0499] 209. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 208, wherein the subject is in need of or has been identified as in need of receiving a vaccine within, for example, 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.

[0500] 210. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 208 or 209, wherein the subject receives a vaccine prior to, simultaneously with, or after administration of the antibody molecule.

[0501] 211. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 210, wherein administration of the antibody molecule reduces the subject's ability to have 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%.

[0502] 212. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 211, wherein administration of the antibody molecule does not reduce or does not substantially reduce the ability of the subject to have an effective antigen-specific serum IgG and / or IgA response to the vaccine.

[0503] 213. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 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.

[0504] 214. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 213, wherein the vaccine comprises a tetanus toxoid, a diphtheria toxoid, or both (e.g. TENIVAC®).

[0505] 215. The antibody molecule, pharmaceutical composition, method for use according to embodiment 214, wherein the subject has or maintains an effective (e.g. protective) level (e.g. equal to or greater than 0.1 IU / mL in the blood) of tetanus and / or diphtheria antitoxoid IgG, 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.

[0506] 216. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 215, wherein the subject has or has been identified as having a genomic susceptibility locus for a disorder, such as IgA nephropathy.

[0507] 217. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 216, further comprising a step of determining whether the subject has a genomic susceptibility locus for a disorder, such as IgA nephropathy.

[0508] 218. 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or An antibody molecule, pharmaceutical composition or method for use according to any of embodiments 160 to 217, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0509] 219. 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; Optionally, the antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 218, wherein the antibody molecule is IgG2.

[0510] 220.Antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 219, wherein the level of ag IgA is determined in a sample from the subject.

[0511] 221. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 220, further comprising a step of determining the level of ag IgA in a sample from the subject.

[0512] 222. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 221, further comprising a step of determining the level of total IgA in the sample.

[0513] 223. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 222, further comprising a step of determining the level of IgM and / or IgG in the sample.

[0514] 224. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 223, further comprising the step of obtaining a sample from a subject.

[0515] 225. The antibody molecule, pharmaceutical composition, method for use according to embodiment 224, wherein the sample is a blood or serum sample.

[0516] 226. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 225, further comprising the step of administering to the subject a second therapeutic agent or treatment modality.

[0517] 227. The antibody molecule, pharmaceutical composition, method for use according to embodiment 226, wherein the second therapeutic agent or therapeutic modality is a small molecule.

[0518] 228. The antibody molecule, pharmaceutical composition, method for use according to embodiment 227, wherein the second therapeutic agent or therapeutic modality is an antibody molecule.

[0519] 229. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 228, wherein the subject is administered the anti-APRIL antibody molecule at a concentration of about 100, 150, 175, 180, 190, 200, 210, 220, 225, 230, 240, 250, or 300 mg / mL.

[0520] 230. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 229, wherein the subject is administered the anti-APRIL antibody molecule at a concentration of about 200 mg / mL.

[0521] 231. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 230, wherein the subject is administered a fixed dose of about 200, 250, 300, 450, 400, 450, 500, 550, 600, 650, 700, 750, or 800 mg of the anti-APRIL antibody molecule.

[0522] 232. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 231, wherein the subject is administered a fixed dose of about 200 mg of the anti-APRIL antibody molecule (e.g. in a volume of about 1 mL).

[0523] 233. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 232, wherein the subject is administered a fixed dose of about 400 mg of the anti-APRIL antibody molecule (e.g. in a total volume of about 2 mL, e.g. as two doses in a volume of 1 mL or as a single dose in a volume of 2 mL).

[0524] 234. The antibody molecule, pharmaceutical composition, method for use according to any of embodiments 160 to 233, wherein the subject is administered a fixed dose of about 600 mg of the anti-APRIL antibody molecule (e.g. in a total volume of about 3 mL, e.g. as one administration in a volume of 2 mL and one administration in a volume of 1 mL).

[0525] 235. The antibody molecule, pharmaceutical composition, or method for use according to any of the preceding embodiments, wherein the subject is administered a fixed dosage of at least 200 mg of the anti-APRIL antibody molecule.

[0526] 236. The antibody molecule, pharmaceutical composition, or method for use according to any of the preceding embodiments, wherein the subject is administered a fixed dosage of 800 mg or less of the anti-APRIL antibody molecule.

[0527] 237. The antibody molecule, pharmaceutical composition, or method for use according to any of the preceding embodiments, wherein the anti-APRIL antibody molecule is administered as a liquid composition.

[0528] 238. A method for improving renal function, comprising administering an anti-APRIL antibody molecule to a subject in need thereof; Thereby improving renal function.

[0529] 239. The method of embodiment 238, wherein the method reverses or prevents the progression of reduced renal function in the subject.

[0530] 240. The method of embodiment 238 or 239, wherein the improved renal function comprises renal regeneration in the subject.

[0531] 241. The method of any of embodiments 238-240, wherein the improved renal function comprises increased estimated glomerular filtration rate (eGFR) in the subject's kidneys.

[0532] 242. The method of any of embodiments 238-241, wherein the improved renal function comprises reduced proteinuria in the subject's kidneys.

[0533] 243. The method of any 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).

[0534] 244. The method of any 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.

[0535] 245. The method of any 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.

[0536] 246. A method for preserving (e.g., maintaining or increasing) estimated glomerular filtration rate (eGFR) in the kidney, 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 a VH and VL of antibody 2419-1406; Thereby preserving (eg, maintaining or increasing) eGFR in the kidney.

[0537] 247. A method for reducing proteinuria in the kidney, comprising administering an anti-APRIL antibody molecule to a subject in need thereof; Thereby reducing proteinuria.

[0538] 248. The method of embodiment 247, wherein the reduction in proteinuria is determined by measuring the urinary protein / creatinine ratio (uPCR), for example, as described in Example 8.

[0539] 249. The method of embodiment 247 or 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).

[0540] 250. The method of embodiment 249, wherein the method reduces proteinuria in the subject within about 3 months after administration.

[0541] 251. The method of embodiment 249, wherein the method reduces proteinuria in the subject within about 6 months after administration.

[0542] 252. The method of embodiment 249, wherein the method reduces proteinuria in the subject within about one year after administration.

[0543] 253. The method of embodiment 249, wherein the method reduces proteinuria in the subject within about 2 years after administration.

[0544] 254. The method of embodiment 249, wherein the method reduces proteinuria in the subject within about 3 years after administration.

[0545] 255. The method of embodiment 249, wherein the method reduces proteinuria in the subject within about 4 years after administration.

[0546] 256. The method of any 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.

[0547] 257. The method of any 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.

[0548] 258. A method for inducing renal recovery, comprising administering an anti-APRIL antibody molecule to a subject in need thereof; Thereby inducing renal recovery.

[0549] 259. A method for inducing kidney regeneration, comprising administering an anti-APRIL antibody molecule to a subject in need thereof; Thereby inducing kidney regeneration.

[0550] 260. A method for reducing an autoantibody response, comprising administering an anti-APRIL antibody molecule to a subject in need thereof; Thereby reducing the autoantibody response.

[0551] 261. 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); VH comprises HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and VL comprises LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 16, or The method of any of the preceding embodiments, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.

[0552] 262. The method of any of the preceding embodiments, wherein the antibody molecule comprises a VH comprising an amino acid sequence of SEQ ID NO: 296, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity 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.

[0553] 263. The method of any of the preceding embodiments, wherein the antibody molecule comprises a VL comprising an amino acid sequence of SEQ ID NO: 286, or an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity 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.

[0554] 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.

[0555] 265. The method of any of the preceding embodiments, wherein the antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region.

[0556] 266. The method of any of the preceding embodiments, wherein the antibody molecule is sibeprenlimab.

[0557] 267. The method of any of the preceding embodiments, wherein the antibody molecule is administered no more than once a month.

[0558] 268. The method of any of the preceding embodiments, wherein the antibody molecule is administered at a dose of 2 mg / kg, 4 mg / kg, or 8 mg / kg.

[0559] 269. The method of any of the preceding embodiments, wherein the antibody molecule is administered once a month, once every two months, or once every three months.

[0560] 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.

[0561] 271. The method of any of the preceding embodiments, wherein the 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.

[0562] 272. The method of any of the preceding embodiments, wherein the antibody molecule is administered intravenously or subcutaneously.

[0563] 273. The method of any of the preceding embodiments, wherein the antibody molecule is administered at a dose of 4 mg / kg, e.g., once a month, and wherein 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 administration (e.g., after the first, second, or third administration).

[0564] 274. The method of any of the preceding embodiments, wherein the antibody molecule is administered at a dose of 8 mg / kg, e.g., once a month, and wherein 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 administration (e.g., after the first, second, or third administration).

[0565] 275. The method of embodiment 273 or 274, 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%, for example, 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 administration (e.g., after the first, second, or third administration).

[0566] 276. The method of any of the preceding embodiments, wherein administration of the antibody molecule results in a decrease in serum IgA levels (e.g., compared to before administration).

[0567] 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.

[0568] 278. The method of embodiment 276 or 277, wherein serum IgA levels are reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, for example, 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 (e.g., after the first, second, or third administration).

[0569] 279. The method of any of embodiments 276-278, wherein serum IgA levels are 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, 35, or 36 months after administration (e.g., after the first, second, or third administration).

[0570] 280. The method of any of the preceding embodiments, wherein administration of the anti-APRIL antibody molecule results in a decrease in serum ag-IgA levels (e.g., compared to before administration).

[0571] 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.

[0572] 282. The method of embodiment 280 or 281, wherein serum ag-IgA levels are reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, for example, 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 (e.g., after the first, second, or third administration).

[0573] 283. The method of any of embodiments 280 to 282, wherein the ag-IgA comprises or is ag IgA1.

[0574] 284. The method of any of the preceding embodiments, wherein administration of the antibody molecule results in a decrease in serum IgG levels (e.g., compared to before administration).

[0575] 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.

[0576] 286. The method of embodiment 284 or 285, wherein serum IgG levels are reduced by at least 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 70%, 75%, 80%, 85%, or 90%, for example, 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 (e.g., after the first, second, or third administration).

[0577] 287. The method of any of embodiments 284-286, wherein serum IgG levels are 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 administration (e.g., after the first, second, or third administration).

[0578] 288. The method of any of the preceding embodiments, wherein administration of the antibody molecule results in a decrease in serum IgM levels (e.g., compared to before administration).

[0579] 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.

[0580] 290. The method of embodiment 288 or 289, wherein serum IgM levels are reduced by at least 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, for example, 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 (e.g., after the first, second, or third administration).

[0581] 291. The method of any of embodiments 288-290, wherein serum IgM levels are 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 administration (e.g., after the first, second, or third administration).

[0582] 292. The method of any of the preceding embodiments, wherein administration of the anti-APRIL antibody molecule results in a decrease in uPCR (e.g., compared to before administration).

[0583] 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.

[0584] 294. The method of embodiment 288 or 289, wherein 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%, for example, 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 (e.g., after the first, second, or third administration).

[0585] 295. The method of any of the preceding embodiments, wherein the subject has or is at risk of having the disorder.

[0586] 296. The method of embodiment 295, wherein the disorder is associated with reduced renal function.

[0587] 297. The method of embodiment 295 or 296, wherein the disorder is treatable by improving renal function.

[0588] 298. The method of any of embodiments 295-297, wherein the subject is at risk for renal failure.

[0589] 299. The method of any of embodiments 295-298, wherein the disorder is a renal disorder, for example, chronic kidney disease (CKD).

[0590] 300. The method of any of embodiments 295-299, wherein the disorder is an autoimmune disorder, such as an autoantibody-associated disorder (e.g., an IgM autoantibody-associated disorder).

[0591] 301. The method of embodiment 300, wherein the autoantibody-associated disorder is primary membranous nephropathy, Goodpasture's disease, or cold agglutinin disease.

[0592] 302. The method of any of embodiments 295-301, wherein the disorder is an IgM-mediated disorder (e.g., IgM neuropathy).

[0593] 303. The method of any of embodiments 295-302, wherein the disorder is glomerulonephritis.

[0594] 304. The method of any of embodiments 295-303, wherein the disease or disorder is IgA nephropathy (IgAN), lupus nephritis, Henoch-Schönlein purpura (HSP, e.g., also referred to as IgA vasculitis (IgAV), 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 neuropathy, post-transplant recurrence of...

Claims

1. 1. An anti-APRIL antibody molecule for use in a method for improving renal function in a subject, comprising: 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or An antibody molecule, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

2. The antibody molecule for use according to claim 1, wherein the method reverses or prevents the progression of reduced renal function in the subject.

3. The antibody molecule for use according to claim 1 or 2, wherein the improved renal function comprises renal regeneration in the subject.

4. The antibody molecule for use according to any of claims 1 to 3, wherein said improved renal function comprises an increased estimated glomerular filtration rate (eGFR) in the kidneys of said subject.

5. The antibody molecule for use according to any of claims 1 to 4, wherein said improved renal function comprises reduced proteinuria in the kidneys of said subject.

6. 6. The antibody molecule for use according to any of claims 1 to 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. 7. The antibody molecule for use according to any 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. 8. The antibody molecule for use according to any of claims 1 to 7, wherein said 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. 1. An anti-APRIL antibody molecule for use in a method of preserving (e.g., maintaining or increasing) estimated glomerular filtration rate (eGFR) in a subject's kidney, comprising: optionally, the average eGFR over a period of at least 12 months following administration of the antibody molecule is equal to or greater than the subject's baseline eGFR; 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or An antibody molecule, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

10. 1. An anti-APRIL antibody molecule for use in a method for reducing proteinuria in the kidney of a subject, comprising: 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or An antibody molecule, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

11. The antibody molecule for use according to claim 10, wherein the reduction in proteinuria is determined by measuring the urinary protein / creatinine ratio (uPCR), e.g. as described in Example 8.

12. 12. The antibody molecule for use according to claim 10 or 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. 13. The antibody molecule for use according to claim 12, wherein the method reduces proteinuria in the subject within about three months of administration.

14. 13. The antibody molecule for use according to claim 12, wherein the method reduces proteinuria in the 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 one year of administration.

16. The antibody molecule for use according to claim 12, wherein the method reduces proteinuria in the subject within about two years of administration.

17. The antibody molecule for use according to claim 12, wherein the method reduces proteinuria in the subject within about three years of administration.

18. The antibody molecule for use according to claim 12, wherein the method reduces proteinuria in the subject within about four years of administration.

19. 19. The antibody molecule for use according to any 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. 20. The antibody molecule for use according to any of claims 10 to 19, wherein said 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. 1. An anti-APRIL antibody molecule for use in a method of inducing renal recovery in a subject, comprising: 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or An antibody molecule, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

22. 1. An anti-APRIL antibody molecule for use in a method of inducing kidney regeneration in a subject, comprising: 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or An antibody molecule, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

23. 1. An anti-APRIL antibody molecule for use in a method of reducing an autoantibody response in a subject, comprising: 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or An antibody molecule, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

24. 20. The antibody molecule for use according to any 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 having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence which differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids.

25. 2. The antibody molecule for use according to any of the preceding claims, wherein the antibody molecule comprises a VL comprising an amino acid sequence of SEQ ID NO: 286, or an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence which differs therefrom by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids.

26. 2. An antibody molecule for use according to any 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. 2. The antibody molecule for use according to any of the preceding claims, wherein said antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region.

28. 2. The antibody molecule for use according to any of the preceding claims, wherein said antibody molecule is sibeprenlimab.

29. 2. The antibody molecule for use according to any of the preceding claims, wherein the antibody molecule is administered no more than once a month.

30. 2. The antibody molecule for use according to any 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. 2. The antibody molecule for use according to any of the preceding claims, wherein said antibody molecule is administered once a month, once every two months or once every three months.

32. 13. The antibody molecule for use according to any 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. 20. The antibody molecule for use according to any of the preceding claims, wherein the 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.

34. 2. The antibody molecule for use according to any of the preceding claims, wherein said antibody molecule is administered intravenously or subcutaneously.

35. 20. The antibody molecule for use according to any of the preceding claims, wherein the antibody molecule is administered at a dose of 4 mg / kg, e.g. once a month, and wherein 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).

36. 20. The antibody molecule for use according to any of the preceding claims, wherein the antibody molecule is administered at a dose of 8 mg / kg, e.g. once a month, and wherein 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).

37. 37. The antibody molecule for use according to claim 35 or 36, 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 said administration (e.g. after the first, second, or third administration).

38. 13. The antibody molecule for use according to any of the preceding claims, wherein administration of the antibody molecule results in a decrease in serum IgA levels (e.g. compared to before said administration).

39. 39. The antibody molecule for use according to 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. 40. The antibody molecule for use according to claim 38 or 39, wherein the serum IgA levels are 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 said administration (e.g. after the first, second, or third administration).

41. 41. The antibody molecule for use according to any of claims 38 to 40, wherein the serum IgA levels are 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, 35, or 36 months after said administration (e.g. after the first, second, or third administration).

42. 13. The antibody molecule for use according to any of the preceding claims, wherein administration of said anti-APRIL antibody molecule results in a decrease in serum a-g-IgA levels (eg compared to before said administration).

43. 43. The antibody molecule for use according to claim 42, wherein the reduction in serum a-g-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. 44. The antibody molecule for use according to claim 42 or 43, wherein said serum a-g-IgA levels are 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 said administration (e.g. after the first, second, or third administration).

45. The antibody molecule for use according to any of claims 42 to 44, wherein the a-g-IgA comprises or is a-g-IgA1.

46. 13. The antibody molecule for use according to any of the preceding claims, wherein administration of the antibody molecule results in a decrease in serum IgG levels (e.g. compared to before said administration).

47. 47. The antibody molecule for use according to 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. 48. The antibody molecule for use according to claim 46 or 47, wherein the serum IgG levels are 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 said administration (e.g. after the first, second, or third administration).

49. 49. The antibody molecule for use according to any of claims 46-48, wherein the serum IgG levels are 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 said administration (e.g. after the first, second, or third administration).

50. 13. The antibody molecule for use according to any of the preceding claims, wherein administration of the antibody molecule results in a decrease in serum IgM levels (e.g. compared to before said administration).

51. 51. The antibody molecule for use according to 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. 52. The antibody molecule for use according to claim 50 or 51, wherein the serum IgM levels are 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 said administration (e.g. after the first, second, or third administration).

53. 53. The antibody molecule for use according to any of claims 50-52, wherein the serum IgM levels are 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 said administration (e.g. after the first, second, or third administration).

54. 13. The antibody molecule for use according to any of the preceding claims, wherein administration of said anti-APRIL antibody molecule results in a decrease in uPCR (e.g. compared to before said administration).

55. 51. The antibody molecule for use according to 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. 52. The antibody molecule for use according to claim 50 or 51, wherein said 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 said administration (e.g. after the first, second, or third administration).

57. 20. The antibody molecule for use according to any of the preceding claims, wherein the subject has or is at risk of having a disorder.

58. 58. The antibody molecule for use according to claim 57, wherein the disorder is associated with reduced renal function.

59. 59. The antibody molecule for use according to claim 57 or 58, wherein the disorder is treatable by improving renal function.

60. The antibody molecule for use according to any of claims 57 to 59, wherein the subject is at risk of renal failure.

61. The antibody molecule for use according to any of claims 57 to 60, wherein the disorder is a renal disorder, such as chronic kidney disease (CKD).

62. 62. The antibody molecule for use according to any of claims 57 to 61, wherein the disorder is an autoimmune disorder, such as an autoantibody associated disorder (such as an IgM autoantibody associated disorder).

63. 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 according to any of claims 57 to 63, wherein the disorder is an IgM mediated disorder (e.g. an IgM neuropathy).

65. The antibody molecule for use according to any of claims 57 to 64, wherein the disorder is glomerulonephritis.

66. 66. The antibody molecule for use according to any of claims 57 to 65, wherein said disease or disorder is IgG nephropathy (IgAN), lupus nephritis, Henoch-Schönlein purpura (HSP, also referred to as IgA vasculitis (IgAV), 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 neuropathy, post-transplant recurrence of glomerular disease, or post-transplant IgA vasculitis.

67. 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 according to claim 66, wherein said disease or disorder is Henoch-Schonlein purpura.

69. The antibody molecule for use according to any of claims 57 to 68, wherein the subject is a pediatric patient (e.g. a patient under the age of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 years old, or a patient aged 0-1, 1-2, 2-3, 3-4, 4-5, 5-10, 10-15, or 15-18 years old).

70. 70. The antibody molecule for use according to claim 69, wherein said disease or disorder is pediatric IgA nephropathy, pediatric Henoch-Schönlein purpura (HSP), pediatric systemic lupus erythematosus (SLE), pediatric lupus nephritis, pediatric atypical hemolytic uremic syndrome (aHUS), pediatric membranoproliferative glomerulonephritis (MPGN), or pediatric ANCA-associated vasculitis.

71. The antibody molecule for use according to any of claims 66 to 70, wherein the subject exhibits an arthritic symptom, a joint pain symptom, a gastrointestinal symptom, and / or a dermatological symptom.

72. 2. The antibody molecule for use according to any of the preceding claims, wherein the subject is a human subject, such as a human patient.

73. 2. The antibody molecule for use according to any of the preceding claims, wherein the subject is not immunocompromised.

74. 74. The antibody molecule for use according to claim 72 or 73, wherein the subject does not have a reduced serum IgG level relative to an average healthy subject (e.g., the subject's serum IgG level is at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% relative to an average healthy subject).

75. 2. The antibody molecule for use according to any of the preceding claims, wherein said subject has a uPCR of 0.75 g / g or a proteinuria of ≧1 g urinary protein / day prior to said administration.

76. 76. The antibody molecule for use according to 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 proteinuria following 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 of said administration).

77. 4. The antibody molecule for use according to any of the preceding claims, wherein the subject is treated with a different anti-APRIL antibody molecule.

78. 20. The antibody molecule for use according to any of the preceding claims, further comprising administering to said subject a second therapeutic agent or treatment modality.

79. 79. The antibody molecule for use of claim 78, wherein the second therapeutic agent comprises a TACI-IgG fusion protein (e.g., telitacicept).

80. 79. The antibody molecule for use according to claim 78, wherein the second therapeutic agent comprises a C1 inhibitor (e.g., a C1s inhibitor, e.g., stimlimab).

81. 79. The antibody molecule for use according to claim 78, wherein the second therapeutic agent is an anti-CD20 antibody (e.g., rituximab).

82. 1. A method of treating IgA nephropathy, said method comprising: responsive to identifying a subject who will benefit from administration of an anti-APRIL antibody molecule, administering an effective amount of said anti-APRIL antibody molecule to said subject; the anti-APRIL antibody molecule is administered no more than once a month; The benefits are as follows: (i) a 90% or greater reduction in the level of APRIL within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of APRIL; (ii) a 60% or greater reduction in the level of galactosyl IgA1 (Gd-IgA1) within 9 months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline level of Gd-IgA; (iii) a 30% or greater reduction in 24-hour urinary protein creatinine ratio (uPCR) within 9 months of administration of the anti-APRIL antibody molecule compared to baseline uPCR in the subject; or (iv) preserving (e.g., maintaining or increasing) the mean eGFR over a period of at least 12 months following 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 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or An antibody molecule, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

83. 83. The antibody molecule for use according to claim 82, wherein the method further comprises identifying a subject who would benefit from administration of the anti-APRIL antibody molecule.

84. 1. An anti-APRIL antibody molecule for use in a method of treating IgA nephropathy in a subject, comprising: the anti-APRIL antibody molecule is to be administered no more than once a month; The administration comprises: (i) a 90% or greater reduction in the level of APRIL within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of APRIL; (ii) a 60% or greater reduction in the level of galactosyl IgA1 (Gd-IgA1) within 9 months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline level of Gd-IgA; (iii) a 30% or greater reduction in 24-hour urinary protein creatinine ratio (uPCR) within 9 months of administration of the anti-APRIL antibody molecule compared to baseline uPCR in the subject; or (iv) preserving (e.g., maintaining or increasing) the mean eGFR over a period of at least 12 months following 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 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or An antibody molecule, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

85. The benefit is (ii) a 60% or greater reduction in the level of galactosyl IgA1 (Gd-IgA1) within 9 months of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of Gd-IgA; and (iv) preserving (e.g., maintaining or increasing) the mean eGFR over a period of at least 12 months following administration of the anti-APRIL antibody molecule compared to the subject's baseline eGFR, or wherein said administration results in (ii) and (iv).

86. The antibody molecule for use according to any of claims 82 to 85, wherein the level of APRIL is reduced by 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more within one month of administration of the anti-APRIL antibody molecule as compared to the subject's baseline level of APRIL.

87. 87. The antibody molecule for use according to any of claims 82 to 86, wherein the level of Gd-IgA1 is reduced by 65%, 70%, 75%, 85%, 90%, 95% or more compared to the subject's baseline level of Gd-IgA within 9 months of administration of the anti-APRIL antibody molecule.

88. The antibody molecule for use according to any of claims 82 to 87, wherein the 24 hour uPCR is reduced by 35%, 40%, 45%, 50%, 55%, 60% or more compared to the subject's baseline uPCR within 9 months of administration of the anti-APRIL antibody molecule.

89. The antibody molecule for use according to any of claims 82-88, wherein the mean eGFR is preserved (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 of claims 82 to 89, wherein the benefit further comprises (v) a reduction in the level of IgG compared to the subject's baseline level of IgG, or wherein the administration further results in (v), optionally wherein the level of IgG is the level of anti-gd-IgA1 IgG.

91. 91. The antibody molecule for use according to any of claims 82-90, wherein the benefit further comprises, or the administration further results in, (vi) a reduction in the level of IgA compared to the subject's baseline level of IgA.

92. The antibody molecule for use according to any of claims 82 to 91, wherein said benefit further comprises, or said administration further results in (vii), a ratio of mean eGFR over a 12 month period after administration of said anti-APRIL antibody molecule to the expected mean eGFR over that 12 month period if said subject had not been administered said anti-APRIL antibody molecule of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

93. The antibody molecule for use according to any of claims 82 to 92, wherein the benefit further comprises, or wherein the administration further results in (vii), (i) not having a 5%, 10%, 15% or more decrease in eGFR compared to the subject's baseline eGFR within one month of administration of the anti-APRIL antibody molecule.

94. The subject, prior to administration of the anti-APRIL antibody molecule, (a) having received angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for at least 3 months; (b) a uPCR level of greater than 0.75 g / g or a 24-hour urinary protein (UP) level of greater than 1.0 g / day; or (c) 30mL / min / 1.73m ２ 94. An antibody molecule for use according to any of claims 82 to 93, having one or more (e.g. two or all) of the eGFRs.

95. The antibody molecule for use according to any 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 subject, prior to administration of the anti-APRIL antibody molecule, (a) a proteinuria level of greater than 2.0 g / day, or (b) 60mL / min / 1.73m ２ 96. An antibody molecule for use according to any of claims 82 to 95, having one or both of the following eGFRs:

97. 1. An anti-APRIL antibody molecule for use in a method of treating IgA nephropathy in a subject, comprising: (a) a proteinuria level of greater than 2.0 g / day; (b) a proteinuria level of greater than 60 mL / min / 1.73 m ２ or (c) having or identified as having both (a) and (b); 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or The VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; Optionally, the anti-APRIL antibody molecule is administered no more than once a month.

98. The anti-APRIL antibody molecule is administered to a subject in need of treatment with (a) a proteinuria level of greater than 2.0 g / day; (b) a proteinuria level of greater than 60 mL / min / 1.73 m ２ 98. The antibody molecule for use according to claim 97, wherein the antibody molecule is administered in response to identification of a subject having an estimated glomerular filtration rate (eGFR) of less than 100 mg / kg / day, or (c) both (a) and (b).

99. The method comprises: (a) a proteinuria level of greater than 2.0 g / day; (b) a proteinuria level of greater than 60 mL / min / 1.73 m ２ 99. The antibody molecule for use according to claim 97 or 98, further comprising identifying subjects having an estimated glomerular filtration rate (eGFR) of less than 100 mg / kg, or (c) both (a) and (b).

100. 100. The antibody molecule for use according to any of claims 82 to 99, wherein the anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence which 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 according to any of claims 82 to 100, wherein said anti-APRIL antibody molecule comprises a VL comprising an amino acid sequence of SEQ ID NO: 286, or an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence which 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 of claims 82 to 101, wherein said 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 of claims 82 to 102, wherein said anti-APRIL antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region.

104. The antibody molecule for use according to any of claims 82 to 103, wherein the anti-APRIL antibody molecule is sibeprenlimab.

105. The antibody molecule for use according to any of claims 82 to 104, wherein said 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 of claims 82 to 105, wherein said 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 according to any of claims 82 to 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 of claims 82 to 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 of claims 82 to 108, wherein said anti-APRIL antibody molecule is administered intravenously or subcutaneously.

110. 1. An anti-APRIL antibody molecule for use in a method of treating IgA nephropathy in a subject, comprising: the subject is being administered a first anti-APRIL antibody molecule at a dose of at least 600 mg once every two weeks, and the administration of the first anti-APRIL antibody is discontinued; a 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or An antibody molecule, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

111. The antibody molecule for use according to claim 110, wherein upon identification of a subject being administered a first anti-APRIL antibody molecule at a dose of at least 600 mg once every two weeks, the administration of the first anti-APRIL antibody molecule is discontinued and the second anti-APRIL antibody molecule is administered.

112. The method further comprising: (a) identifying a subject receiving a first anti-APRIL antibody molecule at a dose of at least 600 mg once every two weeks; 112. The antibody molecule for use according to claim 110 or 111, further comprising: (b) discontinuing said administration of said first anti-APRIL antibody molecule.

113. The antibody molecule for use according to any of claims 110 to 112, wherein the second anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence which 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 according to any of claims 110 to 113, wherein said second anti-APRIL antibody molecule comprises a VL comprising an amino acid sequence of SEQ ID NO: 286, or an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence which 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 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 of claims 110 to 115, wherein said second anti-APRIL antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region.

117. The antibody molecule for use according to any of claims 110 to 116, wherein the second anti-APRIL antibody molecule is sibeprenlimab.

118. The antibody molecule for use according to any 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 of claims 110 to 118, wherein said 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 according to any of claims 110 to 119, wherein 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.

121. The antibody molecule for use according to any of claims 110 to 120, wherein said 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 of claims 110 to 121, wherein said second anti-APRIL antibody molecule is administered intravenously or subcutaneously.

123. The antibody molecule for use according to any of claims 110 to 122, wherein said first anti-APRIL antibody molecule is BION-1301.

124. 1. A method of treating IgA nephropathy, comprising: An anti-APRIL antibody molecule for use in a method comprising administering to a subject in need thereof a second anti-APRIL antibody molecule at a dose of at least 600 mg once every two weeks, the subject has been administered a first anti-APRIL antibody molecule, and the administration of the first anti-APRIL antibody molecule is discontinued; 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or An antibody molecule, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

125. The antibody molecule for use according to claim 124, wherein the second anti-APRIL antibody molecule is administered depending on the identity of the subject receiving the first anti-APRIL antibody molecule.

126. The method further comprising: (a) identifying a subject who has been administered the first anti-APRIL antibody molecule; 126. The antibody molecule for use according to claim 124 or 125, further comprising: (b) discontinuing said administration of said first anti-APRIL antibody molecule.

127. The antibody molecule for use according to any of claims 124 to 126, wherein the first anti-APRIL antibody molecule comprises a VH comprising the amino acid sequence of SEQ ID NO: 296, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence which 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 according to any of claims 124 to 127, wherein said first anti-APRIL antibody molecule comprises a VL comprising an amino acid sequence of SEQ ID NO: 286, or an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence which 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 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 of claims 124 to 129, wherein said first anti-APRIL antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region.

131. The antibody molecule for use according to any of claims 124 to 130, wherein the first anti-APRIL antibody molecule is sibeprenlimab.

132. The antibody molecule for use according to any 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 of claims 124 to 132, wherein said 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 according to any of claims 124 to 133, wherein the first 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.

135. The antibody molecule for use according to any of claims 124 to 134, wherein said 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 of claims 124 to 135, wherein said first anti-APRIL antibody molecule is administered intravenously or subcutaneously.

137. The antibody molecule for use according to any of claims 124 to 136, wherein the second anti-APRIL antibody molecule is BION-1301.

138. 1. An anti-APRIL antibody molecule for use in a method of treating IgA nephropathy in a subject, comprising: the subject is receiving (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 said administration of (i) budesonide, (ii) atrasentan, (iii) dapagliflozin, or (iv) methylprednisolone is discontinued; 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or An antibody molecule, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

139. The antibody molecule for use according to claim 138, wherein the anti-APRIL antibody molecule is administered depending on the identity of a subject receiving (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 method further comprising: (a) identifying a subject receiving (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 according to claim 138 or 139, further comprising: (b) discontinuing the administration of (i) budesonide, (ii) atrasentan, (iii) dapagliflozin, or (iv) methylprednisolone.

141. 1. A method of treating IgA nephropathy, comprising:

13. An anti-APRIL antibody molecule for use in a method 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), the subject is being administered an anti-APRIL antibody molecule, and the administration of the anti-APRIL antibody molecule is discontinued; 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or An antibody molecule, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

142. The antibody molecule for use according to claim 151, wherein (i) budesonide, (ii) atrasentan, (iii) dapagliflozin, or (iv) methylprednisolone is administered depending on the identity of the subject being administered the anti-APRIL antibody molecule.

143. The method further comprising: (a) identifying a subject receiving an anti-APRIL antibody molecule; 153. The antibody molecule for use according to claim 151 or 152, further comprising: (b) discontinuing said administration of said anti-APRIL antibody molecule.

144. The antibody molecule for use according to any 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 having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence which 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 according to any of claims 138 to 144, wherein said anti-APRIL antibody molecule comprises a VL comprising an amino acid sequence of SEQ ID NO: 286, or an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence which 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 of claims 138 to 145, wherein said 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 according to any of claims 138 to 146, wherein said anti-APRIL antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region.

148. The antibody molecule for use according to any of claims 138 to 147, wherein the anti-APRIL antibody molecule is sibeprenlimab.

149. The antibody molecule for use according to any 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 of claims 138 to 149, wherein said 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 according to any of claims 138 to 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 according to any of claims 138 to 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 of claims 138 to 152, wherein said anti-APRIL antibody molecule is administered intravenously or subcutaneously.

154. 1. A method for selecting a subject for a therapy comprising an anti-APRIL antibody molecule, the method comprising: (a) the subject, after monthly administration of the anti-APRIL antibody molecule, (i) a 90% or greater reduction in the level of APRIL within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of APRIL; (ii) a 60% or greater reduction in the level of galactosyl IgA1 (Gd-IgA1) within 9 months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline level of Gd-IgA; (iii) a 30% or greater reduction in 24-hour urinary protein creatinine ratio (uPCR) within 9 months of administration of the anti-APRIL antibody molecule compared to baseline uPCR in the subject; or (iv) determining whether the subject has one or more (e.g., two, three, or all) of the following: preserved (e.g., maintained or increased) 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 said determination that the subject has one or more (e.g., two, three, or all) of (i), (ii), (iii), or (iv) after monthly administration of the anti-APRIL antibody molecule, the subject has or is at risk of having IgA nephropathy; 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or An antibody molecule, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

155. 1. A method for selecting a therapy comprising an anti-APRIL antibody molecule for a subject, the method comprising: (a) the subject, after monthly administration of the anti-APRIL antibody molecule, (i) a 90% or greater reduction in the level of APRIL within one month of administration of the anti-APRIL antibody molecule compared to the subject's baseline level of APRIL; (ii) a 60% or greater reduction in the level of galactosyl IgA1 (Gd-IgA1) within 9 months of administration of the anti-APRIL antibody molecule, compared to the subject's baseline level of Gd-IgA; (iii) a 30% or greater reduction in 24-hour urinary protein creatinine ratio (uPCR) within 9 months of administration of the anti-APRIL antibody molecule compared to baseline uPCR in the subject; or (iv) determining whether the subject has one or more (e.g., two, three, or all) of the following: preserved (e.g., maintained or increased) 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 the determination that the subject has one or more (e.g., two, three, or all) of (i), (ii), (iii), or (iv) after monthly administration of the anti-APRIL antibody molecule, the subject has or is at risk of having IgA nephropathy; 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); the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or An antibody molecule, wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13, and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:

16.

156. The antibody molecule for use according to claim 154 or 155, wherein the anti-APRIL antibody molecule comprises a VH comprising an amino acid sequence of SEQ ID NO: 296, an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence which 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 according to any of claims 154 to 156, wherein said anti-APRIL antibody molecule comprises a VL comprising an amino acid sequence of SEQ ID NO: 286, or an amino acid sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto, or an amino acid sequence which 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 of claims 154 to 157, wherein said 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 according to any of claims 154 to 158, wherein said anti-APRIL antibody molecule comprises an IgG2 heavy chain constant region and a kappa light chain constant region.

160. The antibody molecule for use according to any of claims 154 to 159, wherein the anti-APRIL antibody molecule is sibeprenlimab.

161. The antibody molecule for use according to any of claims 154 to 160, wherein said 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 according to any of claims 154 to 161, wherein said 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 according to any of claims 154 to 162, wherein the anti-APRIL antibody molecule is to be 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.

164. The antibody molecule for use according to any of claims 154 to 163, wherein said 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 of claims 154 to 164, wherein said anti-APRIL antibody molecule is to be administered intravenously or subcutaneously.

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