Methods related to the treatment of kidney disease

Abstract

The present disclosure relates to methods related to the treatment of B-cell responsive autoimmune glomerulopathies.

Description

Attorney Docket No.: VETH-016 / 01WO 327083-2431METHODS RELATED TO THE TREATMENT OF KIDNEY DISEASECROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to US Patent Application No. 63 / 702,149 filed October 1, 2024, the contents of which are hereby incorporated in their entirety by this reference.REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0002] The contents of the electronic sequence listing (VETH_016_01WO_SeqList_ST26.xml; Size: 14,679 bytes; and Date of Creation: September 29, 2025) are herein incorporated by reference in its entirety.BACKGROUND

[0003] Numerous kidney diseases impacting the glomeruli in the nephron (“glomerulopathies”) are traditionally diagnosed by observable symptoms, e.g. proteinuria, hematuria, or histological features (e.g., through tissue samples obtained by biopsy). Glomerulopathies may manifest as nephrotic syndrome (NS), marked by, e.g., swelling (edema) and proteinuria (elevation of protein level in urine), as well as hematuria (blood in urine) in more advanced cases, eventually progressing to kidney failure in some cases. However, glomerulopathies that are classified together based on such traditional diagnostic methods may have an underlying diversity in causes of the disease. Some patients that present with similar observable symptoms may have different causes, and thus different responses to a potential therapy. Current diagnostic techniques do not necessarily provide clinicians with sufficient information to accurately identify what treatments will benefit particular patients. As a result, patients can experience disease progression while undergoing treatments to which they are non-responsive. It is important to not only provide more effective treatments for glomerulopathies, but also better ways of identifying patients that will be responsive to such treatments. In particular, it is possible that certain diseases having an underlying autoimmune cause may have overlapping symptoms with a non-autoimmune-based disease, and thus be diagnosed as the same disease when they are in fact not.

[0004] Examples of such glomerulopathies, which can manifest as nephrotic syndrome, in which classification based on traditional observable symptoms may obfuscate an autoimmune cause for a subset of patients, include membranous nephropathy (MN), Minimal change disease1324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431(MCD), focal segmental glomerulosclerosis (FSGS), frequently relapsing nephrotic syndrome (FRNS), steroid-dependent nephrotic syndrome (SDNS), and steroid resistant nephrotic syndrome (SRNS).

[0005] Membranous nephropathy (MN; also known as membranous glomerulopathy or membranous glomerulonephritis) is a glomerulopathy characterized by thickening of the glomerular basement membrane (GMB) due to the deposition of immune complexes between the GBM and podocytes. This condition leads to damage in the glomeruli, the structures in the kidneys that filter blood. MN is a relatively common cause of NS . In particular, persistent proteinuria (especially with a urine protein: creatinine ratio (UPCR) > 3 mg / mg) is associated with an increased risk of kidney failure. About 80% of cases are primary (or idiopathic) MN (“pMN”) and about 20% are secondary MN associated with other systemic diseases, such as Hepatitis B, lupus erythematosus, cancer, or exposure, such as exposure to NSAIDs. The pathogenesis of pMN is not fully understood. In many cases, pMN is linked to autoimmunity, specifically the presence of autoantibodies targeting phospholipase A2 receptor (PLA2R) or thrombospondin type 1 domain containing 7A (THSD7A), both of which are expressed by podocytes (specialized cells in the kidney that wrap around capillaries and play a key role in glomerular filtration). In a study, 70% of patients with pMN were positive for anti-PLA2R antibodies in serum, and about 3%-5% were positive for anti-THSD7A antibodies in serum. Another 15% of pMN patients, who were negative for anti-PLA2R serum antibodies, had positive staining for PLA2R colocalized with IgG4 in glomerular deposits, indicating recent immunologic disease activity. Another 10% of pMN patients were negative for anti-PLA2A and anti-THSD7A antibodies, and negative for glomerular staining for PLA2R and THSD7A , and therefore had other as yet unidentified causes. (Couser, et al., Clinical Journal of the American Society of Nephrology 12(6):p 983-997, June 2017.)

[0006] Another group of histologically distinct kidney disorder include minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). MCD is characterized by the absence of visible changes in the glomeruli under a light microscope. FSGS, in contrast, involves scarring (sclerosis) in some segments of the glomeruli, visible under light microscopy, and can lead to kidney failure. In particular, persistent proteinuria (e.g., with a urine protein: creatinine ratio (UPCR) > 3 mg / mg) is associated with an increased risk of kidney failure. The pathogenesis of MCD and FSGS is not fully understood. In the case of secondary MCD and FSGS, the disease is2324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 associated with, e.g., infection, drug toxicity, diseases including diabetes or sickle cell disease, obesity, and other glomerulopathies. In the case of primary (or idiopathic) MCD and FSGS, there is no readily known cause.

[0007] Because histological distinctions such as in MCD and FSGS may not have yet had time to emerge in children, the diagnosis of glomerulopathies with manifestations of idiopathic NS (INS) in children is typically based on their response to initial treatment with steroids rather than a histologic diagnosis (as is the case for, e.g., MCD and FSGS). The standard of care for idiopathic NS (INS) in children is to treat empirically with steroids and to reserve diagnostic biopsy only for those who fail to respond to an initial course of steroids or who present at older age (typically > 10 years old) when the likelihood of alternate etiologies is higher. The management of pediatric INS is further characterized based on the response to steroid treatment, namely the ability to achieve complete remission of proteinuria / NS (steroid sensitive vs steroid resistant) and the frequency of relapses occurring after remission (infrequent vs frequently relapsing and / or steroid dependent). Most children (75-80%) with INS achieve remission with initial steroid (e.g., glucocorticoid) therapy, but approximately 30-50% of children develop frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Pediatric INS that do not respond to steroid treatment, is referred to has steroid resistant nephrotic syndrome (SRNS).

[0008] In some cases, MCD and FSDS (which typically present in adults), as well as SDNS, SRNS, and FRNS (which as noted above are diagnosed in children), are linked to autoimmunity, specifically the presence of autoantibodies targeting nephrin. nephrin is known to be expressed by podocytes, and is a transmembrane protein that is located at, and is a component of, the slit diaphragm. The slit diaphragm is a specialized structure found between the foot processes of podocytes that mediates glomerular filtration.

[0009] The above-noted glomerulopathies with autoimmune causes, lack a targeted therapy. Current treatments for the above diseases typically include therapies like corticosteroids, cyclophosphamide, calcineurin inhibitors, or B cell depletion (depending on the particular indication and severity). Angiotensin Converting Enzyme Inhibitors (ACEis) or Angiotensin Receptor Blockers (ARBs) may also be used in cases presenting with proteinuria. However, these treatments come with significant side effects and are not always effective at preventing progression to chronic glomerulopathies or end-stage renal disease. For example, standard of care 3324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 for children with FRNS and SDNS is centered on using broadly immunosuppressive agents such as steroid-sparing therapy, or order to minimize relying on steroid therapy. Exposure of children to broadly immunosuppressive agents, despite complication, has been justified in clinical practice to offset the well-described toxicities associated with long-term steroid exposure. However, the optimal duration of immunosuppressive steroid-sparing therapies to maintain a favorable benefit- to-risk assessment has been a challenge to clinicians and patients / caregivers.

[0010] There is therefore a pressing need for more targeted treatments that can reduce kidney inflammation with fewer adverse effects, particularly in patients with severe or relapsing disease and for those diseases where autoimmunity to auto-antigens are, or contribute to, the underlying cause of the disease. Thus, there is a significant unmet medical need for the treatment of the above glomerulopathies with autoimmune causes because available treatments are currently inadequate. At present, no intervention exists with the potential for true disease modification by reduction of a causal disease factor. In addition, there is a substantial unmet need in accurately diagnosing glomerulopathies and identifying patients with glomerulopathies that may have previously unrecognized autoimmune causes.

[0011] The present disclosure provides compositions and methods that address the abovedescribed problems and needs.SUMMARY

[0012] The present disclosure relates to transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecules and provides methods for identifying and treating a patient having an autoimmune glomerulopathy characterized by the production of autoantibodies to proteins expressed by kidney cells, and related methods.

[0013] According to one aspect, the present disclosure relates to a method of treating a human patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein the TACI-Ig fusion molecule comprises: (i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-4324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431Inducing Ligand); and (ii) a human immunoglobulin-constant domain, wherein the patient has a detectable presence of autoantibodies to nephrin as measured in an immunological assay. Optionally, the B-cell responsive autoimmune glomerulopathy is minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), Relapsing Frequently Nephrotic Syndrome (FRNS), Steroid-Dependent Nephrotic Syndrome (SDNS), or Steroid Resistant Nephrotic Syndrome (SRNS).

[0014] According to another aspect, the present disclosure relates to a TACI)-Ig fusion molecule, wherein the TACI-Ig fusion molecule comprises: (i) a TACI extracellular domain or fragment thereof which binds BAFF and / or APRIL; and (ii) a human immunoglobulin-constant domain, for use in treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the patient has a detectable presence of autoantibodies to nephrin as measured in an immunological assay. Optionally, the B-cell responsive autoimmune glomerulopathy is MCD, FSGS, FRNS, SDNS, or SRNS.

[0015] According to another aspect, the present disclosure relates to a use of a TACI-Ig fusion molecule, wherein the TACI-Ig fusion molecule comprises: (i) a TACI extracellular domain or fragment thereof which binds BAFF and / or APRIL; and (ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence of autoantibodies to nephrin as measured in an immunological assay. Optionally, the B-cell responsive autoimmune glomerulopathy is MCD, FSGS, FRNS, SDNS, or SRNS.

[0016] According to another aspect, the present disclosure relates to a method of treating a human patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein the TACI-Ig fusion molecule comprises: (i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation- Inducing Ligand); and (ii) a human immunoglobulin-constant domain, wherein the patient has a detectable presence of autoantibodies to PLA2R or autoantibodies to THSD7A as measured in an immunological assay. Optionally, the B-cell responsive autoimmune glomerulopathy is membranous nephropathy (MN).5324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0017] According to another aspect, the present disclosure relates to a TACI)-Ig fusion molecule, wherein the TACI-Ig fusion molecule comprises: (i) a TACI extracellular domain or fragment thereof which binds BAFF and / or APRIL; and (ii) a human immunoglobulin-constant domain, for use in treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the patient has a detectable presence of autoantibodies to PLA2R or autoantibodies to THSD7A as measured in an immunological assay. Optionally, the B-cell responsive autoimmune glomerulopathy is MN.

[0018] According to another aspect, the present disclosure relates to a use of a TACI-Ig fusion molecule, wherein the TACI-Ig fusion molecule comprises: (i) a TACI extracellular domain or fragment thereof which binds BAFF and / or APRIL; and (ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the patient has a detectable presence of autoantibodies to PLA2R or autoantibodies to THSD7A as measured in an immunological assay. Optionally, the B-cell responsive autoimmune glomerulopathy is MN.

[0019] According to another aspect, the present disclosure relates to a method of characterizing a B-cell responsive autoimmune glomerulopathy from a plurality of human patients, the method comprising: a. administering, to the plurality of patients having a kidney disease suspected of being a B-cell responsive autoimmune glomerulopathy, a TACI)-Ig fusion molecule, wherein said TACI-Ig fusion molecule comprises: (i) a TACI extracellular domain or fragment thereof which binds BAFF and / or APRIL; and (ii) a human immunoglobulin-constant domain; b. assessing kidney function of the patient after a round of treatment; c. selecting from the plurality of patients a patient that demonstrates improved kidney function after the round of treatment; and d. collecting a serum sample from the selected patient. Optionally, the method further comprises: e. assaying the serum sample for detection of an autoantibody against a protein that is expressed by a kidney cell; and f. characterizing the B-cell responsive autoimmune glomerulopathy of the selected patient based on the detected auto-antibody. Optionally, the detected autoantibody is an anti-nephrin antibody, an anti-PLA2R antibody or an anti- THSD7A antibody. Optionally, the kidney cell is a podocyte, glomerular epithelial cell, or a glomerular mesangial cell.

[0020] According to another aspect, the present disclosure relates to a method of determining a course of treatment for a kidney disease, the method comprising: a. administering to a plurality of human patients having a kidney disease suspected of being a B-cell responsive autoimmune6324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 glomerulopathy, a TACI-Ig fusion molecule, wherein said TACI-Ig fusion molecule comprises: (i) a TACI extracellular domain or fragment thereof which binds BAFF and / or APRIL; and (ii) a human immunoglobulin-constant domain; b. assessing kidney function of the patient after a round of treatment; c. selecting from the plurality of patients a patient that demonstrates improved kidney function after the round of treatment; d. continuing the administration of the TACI-Ig fusion molecule to the patient.

[0021] According to another aspect, the present disclosure relates to a method of identifying a clinical trial candidate for a B-cell responsive autoimmune glomerulopathy, the method comprising: a. administering to a plurality of patients having a glomerulopathy suspected of being a B-cell responsive autoimmune glomerulopathy a TACI-Ig fusion molecule, wherein said TACI- Ig fusion molecule comprises: (i) a TACI extracellular domain or fragment thereof which binds BAFF and / or APRIL; and (ii) a human immunoglobulin-constant domain; b. assessing kidney function of the plurality of patients after a round of treatment; c. selecting from the plurality of patients a patient that demonstrates improved kidney function after the round of treatment; and d. designating the patient as a clinical trial candidate. Optionally, the method further comprises: e. collecting a serum sample from the clinical trial candidate. Optionally, the method further comprises: f. assaying the serum sample for detection of an autoantibody against a protein that is expressed by a kidney cell; g. selecting a clinical trial for a B-cell responsive autoimmune glomerulopathy patient based on the detected autoantibody; and h. designating the clinical trial candidate as a clinical trial participant for the selected clinical trial.BRIEF DESCRIPTION OF THE DRAWINGS

[0022] FIG. 1 is an illustration showing aspects of pathogenesis of anti-PLA2R glomerulopathy.

[0023] FIG. 2 is an illustration showing aspects of pathogenesis of anti-nephrin glomerulopathy.

[0024] FIG. 3 is an illustration showing aspects of pathogenesis of IgAN.

[0025] FIG. 4 is an illustration showing aspects of using TACI-Ig fusion molecules as a tool for patient evaluation and as a research tool.7324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0026] FIG. 5 is an exemplary protocol for the treatment of certain glomerulopathies with atacicept.

[0027] FIG. 6 is an exemplary flow diagram showing aspects of a study (or treatment plan) regarding use of atacicept.DETAILED DESCRIPTIONTACI-Ig fusion molecules

[0028] The methods, compositions, and uses according to the present disclosure involve a TACl-immunoglobulin (TACI-Ig) fusion molecule which comprises (i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor, also known as BLyS (B Lymphocyte Stimulator)) and APRIL (A Proliferation-Inducing Ligand); and (ii) a human immunoglobulin-constant domain.

[0029] To date, three receptors have been identified that have unique binding affinities for the two growth factors BAFF and APRIL: TACI (transmembrane activator and CAML-interactor, also known as also known as tumor necrosis factor receptor superfamily member 13B (TNFRSF13B)), BCMA (B-cell maturation antigen) and BAFF-R (receptor for B-cell activating factor).

[0030] TACI and BCMA bind both BAFF and APRIL, while BAFF-R appears capable of binding only BAFF with high affinity. As a result, BAFF is able to signal through all three receptors, while APRIL only appears capable of signaling through TACI and BCMA. In addition, circulating heterotrimeric complexes of BAFF and APRIL (groupings of three protein subunits, containing one or two copies each of BAFF and APRIL subunits) have been identified in serum samples taken from patients with systemic immune-based rheumatic diseases, and have been shown to induce B-cell proliferation in vitro.

[0031] BAFF and APRIL are potent stimulators of B-cell maturation, proliferation and survival (Moore et al., Science (1999), vol. 285(5425), p. 260-263; Schneider et al., J Exp Med (1999), vol. 189(11), p. 1747-1756; Do et al., J Exp Med (2000), vol. 192(7), p. 953-964) and play a role in the persistence of autoimmune diseases, especially those involving B-cells. Atacicept, an8324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 antagonist for all known conformations of BAFF and APRIL (i.e., homotrimeric, heterotrimeric, multimeric, and soluble or membrane-expressed), deprives B cells of essential survival signals.

[0032] Unless indicated otherwise, if the present disclosure refers to "TACI", this is meant to refer to the human TACI receptor. The amino acid sequence of TACI is provided as SEQ ID NO: 10 of this disclosure.

[0033] The term "TACI extracellular domain" designates the extracellular domain of (human) TACI. The extracellular domain of TACI corresponds to amino acids 1-166 of SEQ ID NO: 10. The amino acid sequence of the extracellular domain of TACI is provided as SEQ ID NO: 11 of this disclosure.

[0034] Whether a TACI extracellular domain or fragment thereof binds to BAFF can be determined by methods known to the skilled person and described, for example, in Example 4 of US Patent Application No. US 2003 / 0103986 Al (herewith incorporated by reference in its entirety).

[0035] It is understood by the person skilled in the art that a TACI-Ig fusion molecule in accordance with the present disclosure is not an anti-TACI antibody. An anti-TACI antibody would not comprise the TACI extracellular domain or a variant or fragment thereof which binds to BAFF and / or APRIL, but would be directed against an epitope from the TACI extracellular domain.

[0036] US Patent Application No. 2006 / 0067933 Al (which is herewith incorporated by reference in its entirety) and international patent application PCT / US02 / 15910 (published as WO 02 / 094852 A2, herewith incorporated by reference in its entirety) disclose sequences for the extracellular domain of TACI as well as specific fragments of the TACI extracellular domain that interact with its ligands, BAFF and APRIL.

[0037] As disclosed e.g., in US Patent Application No. 2006 / 0067933 Al, the TACI extracellular domain comprises two cysteine (Cys)-rich repeats which are characteristic for members of the tumor necrosis factor (TNF) receptor superfamily, to which the TACI receptor belongs. US Patent Application No. 2006 / 0067933 Al, also established that a splice variant of TACI, designated BR42x2, comprising only the second, less conserved Cys-rich repeat, was able to bind to BAFF. Therefore, in the frame of the present disclosure, the TACI extracellular domain9324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 or fragment thereof, in some embodiments, at least comprises or consists of amino acid residues 71 to 104 of SEQ ID NO: 11 corresponding to the second Cys-rich repeat. Alternatively, the TACI extracellular domain or fragment thereof may further comprise amino acid residues 34 to 66 of SEQ ID NO: 11, corresponding to the first Cys-rich repeat. In some embodiments, the TACI extracellular domain or fragment thereof comprises or consists of amino acid residues 30 to 110 of SEQ ID NO: 11. A TACI-Ig fusion molecule comprising this sequence binds to and inhibits BAFF. Moreover, a TACI-Ig fusion molecule comprising this sequence also binds to and inhibits APRIL.

[0038] Fragments and variants (e.g., sequence variants of different % of identity) of the TACI extracellular domain can be used in the context of the present invention as well, so long as the fragment / variant is able to bind BAFF and / or APRIL. In some embodiments, such a fragment also inhibits or reduces the biological activity of BAFF and / or of APRIL.

[0039] The ability of any TACI extracellular domain, TACI-Ig fusion molecule, or any variant or fragment thereof to bind BAFF and / or APRIL can be assessed by standard binding assays known to a skilled person.

[0040] For example, a competitive binding assay can be carried out as described in Example 4 A of published US Patent Application No. US 2003 / 0103986 Al (which is herewith incorporated by reference in its entirety). Briefly, TACI can be coated to a 96 well-plate. Radiolabeled BAFF or APRIL is prepared. Mixtures of the TACI-Ig fusion molecule to be tested, at various concentrations, with a fixed concentration of radiolabeled BAFF or APRIL are exposed to the TACLcoated plate. ICso values can be calculated based on the amount of retained radiolabel.

[0041] Alternatively, a solution binding assay can be carried out as described in Example 4B of published US Patent Application No. US 2003 / 0103986 Al (incorporated herein in its entirety).

[0042] The ability to inhibit or reduce BAFF or APRIL biological activity can be assessed by standard activity assays known to a skilled person, for example by verifying if the TACI extracellular domain or TACI-Ig fusion molecule to be tested causes a dose-dependent reduction in immunoglobulin levels and in mature and total B cells. Such experiments are described for example in Example 11 of published US Patent Application No. 2006 / 0067933 AL10324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0043] The term "human immunoglobulin constant domain", as used herein, may also be referred to as "immunoglobulin (Ig)-constant domain" or an "Fc domain," and is derived from a human , for example, an IgG. The IgG may be an IgGl, IgG2, IgG3 or IgG4. In some embodiments, the Fc domain comprise at least the CH2, CH3 domain of IgGl, and, in certain embodiments, together with the hinge region. In some embodiments, the human immunoglobulin constant domain is a human IgGl constant domain.

[0044] In some embodiments, said human IgGl constant domain has been modified for reduced complement-dependent cytotoxicity (CDC) and / or antibody-dependent cellular cytotoxicity (ADCC).

[0045] In ADCC, the Fc domain of an antibody binds to Fc receptors (FcyRs) on the surface of immune effector cells such as natural killers and macrophages, leading to the phagocytosis or lysis of the targeted cells. In CDC, the antibodies kill the targeted cells by triggering the complement cascade at the cell surface. The binding of IgG to the activating (FcyRI, FcyRIIa, FcyRIIIa and FcyRIIIb) and inhibitory (FcyRIIb) FcyRs or the first component of complement (Clq) depends on residues located in the hinge region and the CH2 domain. Two regions of the CH2 domain are important for FcyRs and complement Clq binding, and have unique sequences in IgG2 and IgG4. For instance, substitution of IgG2 residues at positions 233-236 into human IgGl has been reported to greatly reduce ADCC and CDC. The following Fc mutations, according to EU index positions can, for example, be introduced into an Fc derived from IgGl :T250Q / M428LM252Y / S254T / T256E + H433K / N434FE233P / L234V / L235A / AG236 + A327G / A330S / P331SE333A; K322A.

[0046] Further Fc mutations may include substitutions at one or more of EU index positions selected from 330, 331 234, or 235, or combinations thereof. An amino acid substitution at EU index position 297 located in the CH2 domain may also be introduced into the Fc domain in the context of the present invention, eliminating a potential site of N-linked carbohydrate attachment. The cysteine residue at EU index position 220 may also be replaced with a serine residue, eliminating the cysteine residue that normally forms disulfide bonds with the immunoglobulin light chain constant region.11324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0047] Particular Fc domains suitable for TACI-Ig fusion molecules (Fc-488, as well as Fc4, Fc5, Fc6, Fc7, and Fc8) and their preparation are, for example, disclosed in US Patent No. 8,637,021. For example, for a human immunoglobulin constant domain that may be used in the TACI-Ig fusion molecule of the present disclosure is provided by SEQ ID NO: 2. The use of any of these specific Fc domains or sequence variants thereof for formation of an TACl-lg fusion protein is within the scope of the present disclosure.

[0048] A "TACI-Ig fusion molecule," according to the present disclosure, is a molecule comprising the two parts defined above (i.e., (i) a TACI extracellular domain or fragment thereof which binds BAFF and / or APRIL; and (ii) a human immunoglobulin-constant domain). Such a fusion molecule may be a hybrid protein expressed by a nucleic acid molecule comprising nucleotide sequences of at least two genes. For example, a TACI-Ig fusion molecule can comprise a TACI receptor moiety and an immunoglobulin moiety. As used herein, a "TACI receptor moiety" is a portion of the extracellular domain of the TACI receptor that binds at least one of BAFF or APRIL.

[0049] The term "receptor" denotes a cell-associated protein that binds to a bioactive molecule termed a "ligand." This interaction mediates the effect of the ligand on the cell. In the context of TACI receptor binding, the phrase "specifically binds" or "specific binding" refers to the ability of the ligand to competitively bind with the receptor. For example, BAFF specifically binds with the TACI receptor, and this can be shown by observing competition for the TACI receptor between detectably labeled BAFF and unlabeled BAFF.

[0050] Receptors can be membrane bound, cytosolic or nuclear; monomeric (e.g., thyroid stimulating hormone receptor, beta-adrenergic receptor) or multimeric (e.g., PDGF receptor, growth hormone receptor, IL-3 receptor, GM-CSF receptor, G-CSF receptor, erythropoietin receptor and IL-6 receptor). Membrane-bound receptors are characterized by a multi-domain structure comprising an extracellular ligand-binding domain and an intracellular effector domain that is typically involved in signal transduction. In certain membrane-bound receptors, the extracellular ligand-binding domain and the intracellular effector domain are located in separate polypeptides that comprise the complete functional receptor.

[0051] In general, the binding of ligand to receptor results in a conformational change in the receptor that causes an interaction between the effector domain and other molecule(s) in the cell,12324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 which in turn leads to an alteration in the metabolism of the cell. Metabolic events that are often linked to receptor-ligand interactions include gene transcription, phosphorylation, dephosphorylation, increases in cyclic AMP production, mobilization of cellular calcium, mobilization of membrane lipids, cell adhesion, hydrolysis of inositol lipids and hydrolysis of phospholipids.

[0052] If the present disclosure states that a TACI extracellular domain or fragment thereof "binds" BAFF and / or APRIL, this means that said TACI extracellular domain or fragment thereof binds competitively with the TACI receptor to BAFF and / or APRIL. This binding can be verified by competitive binding experiments as known to a skilled person. For example, to verify binding of a TACI extracellular domain or fragment thereof to BAFF, a fixed amount of labelled BAFF (e.g., with a radiolabel) can be bound to a fixed amount of immobilized full-length TACI receptor in the presence of different amounts of said TACI extracellular domain or fragment thereof. If in the presence of increasing amounts of the TACI extracellular domain or fragment thereof the amount of labelled BAFF bound to said immobilized TACI receptor is decreased, this indicates that said TACI extracellular domain or fragment thereof binds competitively with the TACI receptor to BAFF. Binding of said TACI extracellular domain or fragment thereof to APRIL can be verified by corresponding experiments with labelled APRIL.

[0053] An exemplary TACLIg fusion molecule is atacicept (WHO Drug Information, Vol. 21 (2007) No. 1, p. 58). An amino acid sequence of atacicept is provided as SEQ ID NO: 3. The amino acid sequence of another exemplary TACLIg fusion molecule is provided as SEQ ID NO: 4. The amino acid sequence of further exemplary TACLIg fusion molecules disclosed in published European patent application no. EP 2161287 Al are provided herein as SEQ ID NOs: 5-7 and 9. The amino acid sequence of a further exemplary TACLIg fusion molecule disclosed in US Patent No. US 8,193,316 B2 is provided as SEQ ID NO: 8. The amino acid sequence of a further exemplary TACLIg fusion molecule is provided in Global Substance Registration System - GSRS), record EN2U82XV65, as SEQ ID NO: 12.

[0054] Atacicept is a recombinant fusion protein containing the extracellular, ligand-binding portion of the receptor TACI (Transmembrane activator and calcium modulator and cyclophilin- ligand (CAML)-interactor) and the modified Fc portion of human IgG.13324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0055] Atacicept acts as an antagonist to BAFF (B-lymphocyte stimulator) and APRIL (A proliferation-inducing ligand), both members of the tumor necrosis factor (TNF) superfamily. BAFF and APRIL have been shown to be important regulators of B cell maturation function and survival.

[0056] Atacicept is a soluble glycoprotein containing 313 amino acids, resulting from the fusion of a human IgGl-Fc and a portion from the extracellular domain of the BAFF receptor TACI, with a predicted mass of 35.4 kilodalton (kDa). The product conformation is dimeric, with a predicted mass of 73.4 kDa. Atacicept may be produced in Chinese Hamster Ovary (CHO) cells by recombinant technology.

[0057] In atacicept, the human IgGl-Fc was modified to reduce Fc binding to the Clq component of complement and the interaction with antibody receptors. Atacicept was tested and confirmed for reduction of these Fc effector functions.

[0058] In certain embodiments within the context of the present invention, any such fragment or variant of a TACI extracellular domain of the disclosure or a TACLIg fusion molecule of the disclosure, does not have any biological activity which is significantly lower than that of atacicept, i.e., a protein having the amino acid sequence of SEQ ID NO: 3.

[0059] The TACLIg fusion molecules of the disclosure may be prepared by standard methods of molecular biology, recombinant protein expression and purification known to the skilled person. Such methods are for example described in US Patent Application No. 2003 / 0103986 Al. Specifically, a nucleic acid encoding the protein sequence of the TACLIg fusion molecule can be prepared, either by DNA synthesis or by a method as described in Example 1 of US Patent Application No. 2003 / 0103986 Al. Subsequently, this nucleic acid can be cloned into a mammalian expression vector, e.g. as described in Example 2 of US Patent Application No. 2003 / 0103986 Al. The expression construct can then be used to transfect mammalian expression cells, e.g. Chinese hamster ovary (CHO) DG44 cells, and to recombinantly express the TACLIg fusion molecule encoded the expression construct, as described in Example 2 of US Patent Application No. 2003 / 0103986 AL The recombinantly expressed protein can then be isolated and purified e.g. by a combination of protein A affinity chromatography and S-200 size exclusion chromatography, as described in Examples 2 and 3 of US Patent Application No. 2003 / 0103986 Al. Structural characterization of the purified TACLIg fusion molecule may be14324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 carried out by Western blotting and protein sequencing as described in Example 3 of US Patent Application No. 2003 / 0103986 Al. Moreover, a functional characterization of the TACI-Ig fusion molecule can be carried out by competitive binding assays or solution binding assays as described in Example 4 of US Patent Application No. 2003 / 0103986 Al. Recombinant antibodies or other Fc-containing proteins produced in CHO cells often undergo C-terminal lysine clipping, a post- translational modification where a terminal lysine residues on the Fc are enzymatically removed. The TACI-Ig fusion molecules as described herein comprises an Ig Fc region, that typically has a C-terminal lysine. As such, the TACI-Ig fusion molecules produced in CHO cells may be subject to the C-terminal lysine clipping, and the final product of the TACI-Ig fusion molecules may comprise a mix of molecules with and without the C-terminal lysine.

[0060] In some embodiments, said TACI extracellular domain or fragment thereof has an amino acid sequence that is at least 80%, at least 90%, or at least 95% identical to SEQ ID NO: 1. In some embodiments, the TACI extracellular domain or fragment thereof has an amino acid sequence comprising SEQ ID NO: 1. In some embodiments, the TACI extracellular domain or fragment thereof has an amino acid sequence consisting of SEQ ID NO: 1.

[0061] If the present disclosure states that a certain sequence A "is at least x % identical" to another sequence B, this is synonymous to the statement that sequence A "has x % identity" to sequence B. The statement reflects a relationship between the two polypeptide sequences A and B determined by comparing the sequences. In general, identity refers to an exact amino acid to amino acid correspondence of the two polypeptide sequences, respectively, over the length of the sequences being compared. For sequences where there is not an exact correspondence, a percentage to which the two sequences are identical may be determined. In general, the two sequences to be compared are aligned to give a maximum correlation between the sequences. This may include inserting "gaps" in either one or both sequences, to enhance the degree of alignment. A % identity may be determined over the whole length of each of the sequences being compared (so-called global alignment), that is particularly suitable for sequences of the same or very similar length, or over shorter, defined lengths (so-called local alignment), that is more suitable for sequences of unequal length.

[0062] Methods for comparing the identity of two or more sequences are well known in the art. Thus, for instance, programs available in the Wisconsin Sequence Analysis Package, version 9.1, for example the programs BESTFIT and GAP, may be used to determine the % identity between 15324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 two polynucleotides and the % identity between two polypeptide sequences. BESTFIT uses a "local homology" algorithm and finds the best single region of similarity between two sequences. Other programs for determining identity sequences are also known in the art, for instance the BLAST family of programs and FASTA. In some embodiments, % identity according to the present disclosure is determined according to the BLAST family of programs.

[0063] In some embodiments, said human immunoglobulin-constant domain has an amino acid sequence that is at least 80%, at least 90%, or at least 95% identical to SEQ ID NO: 2, optionally without the C-terminal lysine. In certain embodiments, said human immunoglobulin-constant domain has an amino acid sequence comprising SEQ ID NO: 2, optionally without the C-terminal lysine. In particular embodiments, said human immunoglobulin-constant domain has an amino acid sequence consisting of SEQ ID NO: 2, optionally without the C-terminal lysine.

[0064] In some embodiments, said TACLIg fusion molecule has an amino acid sequence that is at least 80%, at least 90%, or at least 95% identical to SEQ ID NO: 3. It will be appreciated that an amino acid sequence that is at least 80%, at least 90%, or at least 95% identical to SEQ ID NO: 3 includes an amino acid sequence of SEQ ID NO: 3 without the C-terminal lysine. In some embodiments, said human immunoglobulin-constant domain has an amino acid sequence comprising SEQ ID NO: 3, optionally without the C-terminal lysine. In some embodiments, said human immunoglobulin-constant domain is atacicept, having an amino acid sequence consisting of SEQ ID NO: 3, optionally without the C-terminal lysine (e.g. that which may be post- translationally clipped during production in certain cell lines).

[0065] In some embodiments, said TACLIg fusion molecule has an amino acid sequence that is at least 80%, preferably at least 90%, or at least 95% identical to SEQ ID NO: 4. It will be appreciated that an amino acid sequence that is at least 80%, at least 90%, or at least 95% identical to SEQ ID NO: 4 includes an amino acid sequence of SEQ ID NO: 4 without the C- terminal lysine. In some embodiments, said human immunoglobulin-constant domain has an amino acid sequence comprising SEQ ID NO: 4, optionally without the C-terminal lysine. In some embodiments, the human immunoglobulin-constant domain has an amino acid sequence consisting of SEQ ID NO: 4, optionally without the C-terminal lysine.

[0066] In some embodiments, said TACLIg fusion molecule has an amino acid sequence that is at least 80%, least 90%, or at least 95% identical to at least one of SEQ ID NOS: 5-9. It will be16324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 appreciated that an amino acid sequence that is at least 80%, at least 90%, or at least 95% identical to at least one of SEQ ID NOS: 5-9 includes an amino acid sequence of at least one of SEQ ID NOS: 5-9 without the C-terminal lysine. In some embodiments, said TACI-Ig fusion molecule has an amino acid sequence comprising at least one of SEQ ID NOS: 5-9, optionally without the C-terminal lysine. In some embodiments, said TACI-Ig fusion molecule has an amino acid sequence consisting of one of SEQ ID NOS: 5-9, optionally without the C-terminal lysine.

[0067] In some embodiments, said TACI-Ig fusion molecule has an amino acid sequence that is at least 80%, at least 90%, or at least 95% identical to SEQ ID NO: 12. It will be appreciated that an amino acid sequence that is at least 80%, at least 90%, or at least 95% identical to SEQ ID NO: 12 includes an amino acid sequence of SEQ ID NO: 12 without the C-terminal lysine. In some embodiments, said human immunoglobulin-constant domain has an amino acid sequence comprising SEQ ID NO: 12, optionally without the C-terminal lysine. In some embodiments, the human immunoglobulin-constant domain has an amino acid sequence consisting of SEQ ID NO: 12, optionally without the C-terminal lysine.Indications

[0068] The TACI-Ig fusion molecules of the disclosure are useful in treating certain indications, including B-cell responsive autoimmune glomerulopathies, as described herein.

[0069] As used herein, a “B-cell responsive autoimmune glomerulopathy” refers to glomerulopathies characterized by the production of autoantibodies to proteins expressed by kidney cells (e.g., proteins occurring on / in podocytes, glomerular epithelial cells, glomerular mesangial cells, etc.). Exemplary autoantibodies include, for example, but are not limited to, anti- PLA2R antibodies, anti-THSD7A antibodies, and anti-nephrin antibodies. PLA2R, THSD7A, and nephrin are membrane-bound proteins that are expressed by podocytes. While not being bound by theory, the binding of the autoantibodies to the target protein (e.g., PLA2R, nephrin, etc.) leads to a local inflammatory process within the glomerulus that may interfere with normal kidney function.

[0070] In some embodiments, the B-cell responsive autoimmune glomerulopathy may be characterized in a patient by a detectable presence of certain autoantibodies in the patient, for example in a serum sample or a kidney biopsy of the patient, e.g. of one or more autoantibodies17324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 to proteins expressed by kidney cells (e.g., anti-nephrin antibodies). The autoantibodies may be detected by any autoantibody assay known in the art, for example an immunological assay. The immunological assay may be, e.g., immunofluorescence assay (IIF), enzyme-linked immunosorbent assay (ELISA), nephelometry or immunoblotting (Aggarwal, “Role of autoantibody testing”, Best Practice & Research Clinical Rheumatology, Volume 28, Issue 6, 2014). Detectable presence may be an autoantibody titer that is above a threshold value, e.g., > 10 Relative Units per milliliter (RU / ml), > 15 RU / ml, > 20 RU / ml, or > 25 RU / ml. In some embodiments, the autoantibody is assayed in a serum sample of the patient or in a kidney biopsy of the patient.

[0071] In certain embodiments, the presence of autoantibodies in a biological sample (e.g., serum or kidney biopsy sample) may be determined using an immunoblotting-based assay. By way of example, for detecting anti-nephrin autoantibodies, the method may comprise incubating the biological sample with a recombinant human nephrin ectodomain protein, optionally comprising amino acid residues A36 through L1052. The incubation may be carried out under conditions suitable for antibody-antigen binding, such as overnight incubation at 4°C, so that any anti-nephrin autoantibodies in the biological sample will have an opportunity to bind to the recombinant human nephrin. Following incubation, a protein G reagent, which has a high affinity for the Fc region of immunoglobulin G (IgG) antibodies from various species including humans, may be added to facilitate the capture of antibody-antigen complexes. The resulting immune- precipitates may be collected, subjected to electrophoresis (e.g., SDS-PAGE), and transferred to a membrane for immunoblot analysis. Detection of nephrin within the immune-precipitates may be performed using an anti-nephrin antibody, such as AF4269 (available from R&D Systems), or any suitable alternative.

[0072] A similar immunoblotting-based approach may be used to detect anti-PLA2R autoantibodies by using an appropriate recombinant human PLA2R antigen (e.g., comprising a full coding region or an extracellular portion thereof) and an appropriate anti-PLA2R antibody, or to detect anti-THSD7A autoantibodies by using an appropriate recombinant human THSD7A antigen (e.g. comprising a full coding region or an extracellular portion thereof) and an appropriate anti-THSD7A antibody.

[0073] In certain embodiments, the presence of autoantibodies in a biological sample (e.g., serum or kidney biopsy sample) may be determined using an ELISA-based assay. By way of 18324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 example, for detecting anti-PLA2R autoantibodies, the method may involve coating a solid support, such as an ELISA plate, with recombinant PLA2R protein (e.g. a full coding region aa 20-1399 or an extracellular portion thereof) under suitable buffer conditions. After blocking to prevent non-specific binding, patient serum (or kidney biopsy sample) may be applied to the coated surface at a selected dilution. Following incubation, the plate may be washed and treated with a secondary antibody conjugated to an enzyme such as horseradish peroxidase that binds to human immunoglobulin e.g., an anti-human IgG-HRP conjugate (e.g., from Jackson ImmunoResearch, Newmarket, UK or a suitable alternative thereof). A chromogenic substrate may then be added to generate a detectable signal, which may be quantified by measuring absorbance at an appropriate wavelength (e.g., 450 nm). Antibody concentrations may be determined by comparison to a standard curve generated from known reference samples.

[0074] A similar ELISA-based approach may be used to detect anti-nephrin autoantibodies by using an appropriate recombinant human nephrin antigen (e.g., comprising a full coding region or an extracellular portion thereof), or to detect anti-THSD7A autoantibodies by using an appropriate recombinant human THSD7A antigen (e.g. comprising a full coding region or an extracellular portion thereof).

[0075] In some embodiments, the protein expressed by the kidney cells may be PLA2R, nephrin, or THSD7A. In some embodiments, the protein expressed by the kidney cells may be nephrin, or THSD7A. As such, in some embodiments, the autoantibodies may be anti-PLA2R antibodies, anti-nephrin antibodies, or anti-THSD7A antibodies.

[0076] In some embodiments, the protein expressed by kidney cells occurs on / in podocytes, glomerular epithelial cells, glomerular mesangial cells, etc.). In some embodiments, the protein expressed by kidney cells is a protein comprised in the slit diaphragm (a “slit diaphragm protein”), e.g., nephrin or THSD7A. In some embodiments, the protein expressed by the kidney cells is a protein expressed by glomerular mesangial cells.

[0077] A B-cell responsive autoimmune glomerulopathy may be categorized and referred to by an autoantibody whose presence in a patient is associated with presentation of glomerulopathy. As such, for example, a B-cell responsive autoimmune glomerulopathy associated with the presence of anti-PLA2R antibodies may be referred to herein as an “anti-PLA2R glomerulopathy”, and a B-cell responsive autoimmune glomerulopathy associated with the19324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 presence of anti-nephrin antibodies may be referred to herein as an “anti-nephrin glomerulopathy”.

[0078] In some embodiments, the B-cell responsive autoimmune glomerulopathy may be an anti-PLA2R glomerulopathy, an anti-THSD7A glomerulopathy, or an anti-nephrin glomerulopathy. In some embodiments, the anti-PLA2R glomerulopathy or anti-THSD7A glomerulopathy may be a pMN. In some embodiments, the anti-nephrin glomerulopathy may be an adult anti-nephrin glomerulopathy, e.g., a MCD or a FSGS. In some embodiments, the anti- nephrin glomerulopathy may be an juvenile anti-nephrin glomerulopathy, e.g., a FRNS, a SDNS, or a SRNS).

[0079] FIG. 1 schematically shows a summary of aspects of pathogenesis and disease progression an anti-PLA2R glomerulopathy. Without wishing to be bound by theory, for reasons that have not yet been fully elucidated, B cells can abnormally begin producing antibodies against PLA2R (which, as noted above, are expressed by podocytes). The presence of anti-PLA2 antibodies at the glomerulus, and the interaction with the antibodies with PLA2R expressed by the podocytes may lead to, among other things, cytoskeletal dysregulation in podocytes and local inflammatory processes within the glomerulus. If the condition progresses, and is left unaddressed, the downstream effect may be histological changes and proteinuria characteristic of primary membranous nephropathy (pMN).

[0080] FIG. 2 schematically shows a summary of aspects of pathogenesis and disease progression an anti-nephrin glomerulopathy. Without wishing to be bound by theory, for reasons that have not yet been fully elucidated, B cells can abnormally begin producing antibodies against nephrin (which, as noted above, is a major component of the slit diaphragm). The presence of anti-nephrin antibodies at the glomerulus, and the interaction of the antibodies with nephrin may lead to, among other things, cytoskeletal dysregulation / degradation in podocytes and nephrin endocytosis, and local inflammatory processes within the glomerulus. If the condition progresses, and is left unaddressed, the downstream effect may be nephrotic syndrome, including histological changes and proteinuria characteristic of MCD, and in more severe cases, FSGS, as well as pediatric nephrotic syndromes of FRNS, SDNS, and SRNS.

[0081] Without wishing to be bound by theory, it will be appreciated that B-cell responsive autoimmune glomerulopathies are distinct from certain other autoimmune glomerulopathies, such20324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 as IgA Nephritis (IgAN) or IgA Vasculitis Nephritis (IgAVN), in which a characteristic feature is the production by the B-cells of both the autoantigen and the autoantibody that contribute to pathogenesis: (1) galactose-deficient IgAl (Gd-IgAl), an aberrantly glycosylated form of Immunoglobulin Al (IgAl), and (2) anti-Gd-IgAl autoantibodies (with the Gd-IgAl functioning as the autoantigen). See FIG. 3, which summarizes aspects, including the immunological aspects of the pathogenesis and disease progression of IgAN.

[0082] A patient having a B-cell responsive autoimmune glomerulopathy in need of treatment typically has an indication of insufficient or abnormal kidney function, e.g., proteinuria or low eGFR (estimated glomerular flow rate).

[0083] Proteinuria is a condition characterized by increased protein in urine, and may, e.g., be measured as urine protein to creatinine ratio (UPCR; mg protein / mg creatine). In some embodiments, the UPCR may be determined from a urine specimen, e.g. a 24-hour urine specimens. A UPCR of < 0.15 mg / mg is typically considered normal in human patients, whereas: a UPCR of > 0.15 mg / mg and < 0.5 mg / mg is typically considered mild proteinuria; a UPCR of > 0.5 mg / mg and < 3 mg / mg is typically considered moderate proteinuria; and a UPCR of > 3 mg / mg is typically considered nephrotic-range proteinuria.

[0084] In some embodiments, the patient in need of treatment has proteinuria as measured by urine protein to creatinine ratio (UPCR; mg protein / mg creatine), at least 0.5 mg / mg, at least 0.75 mg / mg, at least 1.0 mg / mg, at least 1.5 mg / mg, at least 2 mg / mg, at least 2.5 mg / mg, at least 3 mg / mg, at least 3.5 mg / mg, at least 4 mg / mg, at least 5 mg / mg, at least 6 mg / mg, between about 0.5 mg / mg and about 1 mg / mg, between 0.5 mg / mg and 2 mg / mg, between 0.5 mg / mg and 3 mg / mg, between 0.5 mg / mg and 4 mg / mg, between 0.5 mg / mg and 5 mg / mg, between 0.5 mg / mg and about 6 mg / mg, between about 0.75 mg / mg and about 1 mg / mg, between about 0.75 mg / mg and about 2 mg / mg, about between 0.75 mg / mg and about 3 mg / mg, between about 0.75 mg / mg and about 4 mg / mg, between about 0.75 mg / mg and about 5 mg / mg, between about 0.75 mg / mg and about 6 mg / mg, between about 1 mg / mg and about 2 mg / mg, between about 1 mg / mg and about 3 mg / mg, between about 1 mg / mg and about 4 mg / mg, between about 1 mg / mg and about 5 mg / mg, between about 1 mg / mg and about 6 mg / mg, between about 2 mg / mg and about 3 mg / mg, between about 2 mg / mg and about 4 mg / mg, between about 2 mg / mg and about 5 mg / mg, or between 2 about mg / mg and about 6 mg / mg, between about 3 mg / mg and about 4 mg / mg, between about 3 mg / mg and about 5 mg / mg, or between about 3 mg / mg and about 6 mg / mg.21324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0085] eGFR is a calculated value used to assess how well the kidneys are filtering waste and excess fluids from the blood. It is derived from a blood test that measures serum creatinine or cystatin C, and incorporates various factors to estimate kidney function, and is a well-known indicator for diagnosing and staging chronic kidney disease (CKD). Example formulas for calculating eGFR includes a CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation (e.g., a CKD-EPI-2021 eGFRcr-cys equation) for patients >18 years of age, or a CKiD U25 (Chronic Kidney Disease in Children, under 25) calculator for younger patients, e.g., < 18 years of age. Observed values and changes from baseline in eGFR may be summarized at nominal timepoints using descriptive statistics. The change from baseline in eGFR may also be estimated by MMRM modeling. eGFR is typically expressed in ml / min / 1.73 m2, representing the volume of blood filtered per minute per standardized body surface area. In some embodiments, the stages of chronic kidney disease (CKD) may be assessed based on eGFR as shown below in Table 1 :Table 1 : CKD stage and eGFR

[0086] In some embodiments, the patient in need of treatment is at CKD stage 2, CKD stage 3a, CKD stage 3b, or CKD stage 3 (combination of states 3a and 3b). In some embodiments, the patient in need of treatment has an eGFR of < 90 milliliters per minute per 1.73 square meters of body surface area (ml / min / 1.73m2), < 80 ml / min / 1.73m2, < 70 ml / min / 1.73m2, < 60 ml / min / 1.73m2, < 45 ml / min / 1.73m2, between about 90 ml / min / 1.73m2and about 60 ml / min / 1.73m2, between about 90 ml / min / 1.73m2and about 45 ml / min / 1.73m2, between about 90 ml / min / 1.73m2and about 30 ml / min / 1.73m2, between about 60 ml / min / 1.73m2and about 4522324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 ml / min / 1.73m2, between about 60 ml / min / 1.73m2and about 30 ml / min / 1.73m2, or between about 45 ml / min / 1.73m2and about 30 ml / min / 1.73m2.

[0087] In some embodiments, thew patient in need of treatment is not in stage 4 or 5, thus having an eGFR of > 30 ml / min / 1.73m2.

[0088] In some embodiments, e.g., in more severe / progressed cases of the diseases, the patient in need thereof may have hematuria. In some embodiments, hematuria categories (negative / trace, 1+, 2+, or 3+) may be defined based on occult blood results from dipstick test.

[0089] In some embodiments, the patient in need of treatment may have been treated by another therapeutic agent, prior to treatment with the TACI-Ig fusion molecule, optionally for at least 12 weeks or for at least 8 weeks, optionally at a stable dose, optionally at the maximum labeled or tolerated dose. In some embodiments, the patient continues to receive a stable dose of the another therapeutic agent during treatment with the TACI-Ig fusion molecule. In some embodiments, the patient in need of treatment may be initiated into treatment with the another therapeutic agent, concomitantly with the TACI-Ig fusion molecule, optionally at the maximum labeled or tolerated dose. In some embodiments, the another therapeutic agent is a renin-angiotensin-aldosterone system inhibitor (RAASi), e.g., an angiotensin converting enzyme inhibitor (ACEi) and / or angiotensin II receptor blocker (ARB). In some embodiments, the another therapeutic agent is a sodium-glucose cotransporter-2 inhibitors (SGLT2i), a mineralocorticoid receptor antagonist (MRA), an endothelin receptor antagonists (ERA) or a glucagon-like peptide- 1 receptor agonist (GLP-1RA).

[0090] In some embodiments, the patient in need of treatment may be an adult, at > 18 years of age. In some embodiments, the patient in need of treatment may be a juvenile >10 to < 18 years of age. In some embodiments, the patient in need of treatment may have a weight of 40 kg or greater. In some embodiments, the patient in need of treatment may have a weight of less than 40 kg-

[0091] In some embodiments, the patient does not exhibit evidence of rapidly progressive glomerulonephropathy, optionally defined as a loss of > 50% of estimated glomerular filtration rate (eGFR) within 3 months prior to and at Screening.

[0092] In some embodiments, the patient does not have acute kidney injury.23324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0093] In some embodiments, the patient does not have severe kidney impairment, such as eGFR < 15 ml / min / 1.73m2, or require dialysis or kidney replacement therapy.

[0094] In some embodiments, the patient has not undergone kidney transplantation or other organ transplantation prior to the study and is not expected to undergo such transplantation during the study, with the exception of corneal transplants.

[0095] In some embodiments, the patient does not have uncontrolled diabetes.

[0096] In some embodiments, the patient does not have a history of tuberculosis (TB), untreated latent TB infection (LTBI), or evidence of LTBI.

[0097] In some embodiments, the patient does not present with clinically significant or predefined blood abnormalities, such as serum IgG, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, hemoglobin, platelet count, or neutrophil count beyond threshold levels.

[0098] In some embodiments, the patient does not have a prior or current history of IgA-related disease, e.g., Gd-IgAl -related disease, including IgAN, IgA Vasculitis Nephritis (IgAVN), or IgA vasculitis.

[0099] In some embodiments, the patient does not have intestinal complications such as intussusception, gastrointestinal hemorrhage requiring transfusion, intestinal ischemia, perforation, or abdominal pain persisting more than one day and unresponsive to standard analgesics (e.g., acetaminophen and / or NSAIDs).

[0100] In some embodiments, the patient does not have an active, clinically significant viral, bacterial, or fungal infection, chronic infections, or cancer.

[0101] In some embodiments, the patient has a relapsing B-cell responsive autoimmune glomerulopathy, or a B-cell responsive autoimmune glomerulopathy that is resistant to treatment by alternative immunosuppressants for example with anti-CD20 antibody therapy (e.g. rituximab).24324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0102] In some embodiments, the patient is not receiving concomitant treatment with anti- CD20 antibody therapy (e.g. rituximab) or alkylating agents, including but not limited to cyclophosphamide.

[0103] In some embodiments, the patient has a normal B cell count that is above the lower limit of normal (LLN) for age. In some embodiments, normal B-cell count may be defined as 1000 and 4800 lymphocytes per pL of blood.

[0104] In some embodiments, the relevant autoantibody, e.g., anti-PLA2R autoantibody for a patient with anti-PLA2R glomerulopathy or anti-nephrin autoantibody for a patient with anti- nephrin glomerulopathy, did not exhibit an acute reduction in the patient, such as >50% in the 6 months prior to Screening.Methods of treatment

[0105] In some embodiments, a patient having a B-cell responsive autoimmune glomerulopathy in need of treatment may be treated with an administration of a therapeutically effective amount of a TACI-Ig fusion molecule as described herein (e.g., atacicept).

[0106] If the present disclosure states that the TACI-Ig fusion molecule is administered to a patient / subject in need thereof, it is understood that this means that a therapeutically effective amount of said TACI-Ig fusion molecule is administered. A TACI-immunoglobulin protein and a pharmaceutically acceptable carrier is said to be administered in a "therapeutically effective amount" if the amount administered is physiologically significant. An agent is physiologically significant if its presence results in a detectable change in the physiology of a recipient patient. One example of a general indication that a TACI- immunoglobulin protein is administered in a therapeutically effective amount is that, following administration to a subject, there is a decrease in circulating levels of BAFF and / or APRIL in the blood. The level of circulating levels of BAFF and / or APRIL in the blood can for example be determined by an ELISA.

[0107] In some embodiments, the TACI-Ig fusion molecule is administered at a dose of between about 75 mg per week and about 150 mg per week, between about 75 mg per week and about 200 mg per week, between about 100 mg per week and about 150 mg per week, between about 100 mg per week and about 200 mg per week, about 75 mg per week, about 100 mg per25324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 week, about 125 mg per week, about 150 mg per week, about 175 mg per week, or about 200 mg per week.

[0100] In some embodiments, the TACI-Ig fusion molecule is administered at a monthly administration that is equivalent to between about 75 mg per week and about 150 mg per week, between about 75 mg per week and about 200 mg per week, between about 100 mg per week and about 150 mg per week, between about 100 mg per week and about 200 mg per week, about 75 mg per week, about 100 mg per week, about 125 mg per week, about 150 mg per week, about 175 mg per week, or about 200 mg per week.

[0101] In some embodiments, the TACI-Ig fusion molecule is administered at a dose of between about 300 mg per month and about 800 mg per month, between about 300 mg per month and about 350 mg per month, between about 300 mg per month and about 400 mg per month, between about 300 mg per month and about 450 mg per month, between about 300 mg per month and about 500 mg per month, between about 300 mg per month and about 600 mg per month, between about 300 mg per month and about 700 mg per month, between about 350 mg per month and about 400 mg per month, between about 350 mg per month and about 450 mg per month, between about 350 mg per month and about 500 mg per month, between about 350 mg per month and about 600 mg per month, between about 350 mg per month and about 700 mg per month, between about 350 mg per month and about 800 mg per month, between about 400 mg per month and about 450 mg per month, between about 400 mg per month and about 500 mg per month, between about 400 mg per month and about 600 mg per month, between about 400 mg per month and about 700 mg per month, between about 400 mg per month and about 800 mg per month, between about 450 mg per month and about 500 mg per month, between about 450 mg per month and about 600 mg per month, between about 450 mg per month and about 700 mg per month, between about 450 mg per month and about 800 mg per month, between about 500 mg per month and about 600 mg per month, between about 500 mg per month and about 700 mg per month, between about 500 mg per month and about 800 mg per month, between about 600 mg per month and about 700 mg per month, between about 600 mg per month and about 800 mg per month, between about 700 mg per month and about 800 mg per month, about 300 mg per month, about 350 mg per month, about 400 mg per month, about 450 mg per month, about 500 mg per month, about 550 mg per month, about 600 mg per month, about 650 mg per month, about 700 mg per month, about 750 mg per month, or about 800 mg per month.26324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0102] The dose administered may depend on the weight of the patient. In some embodiments, the doses noted above may be administered to patients that weigh 40 kg or more. In some embodiments, a patient that weighs less than 40 kg may be administered a dose that is half of what is administered to patients that weigh 40 kg or more. For example, in a treatment where patients that weigh 40 kg or more are administered a dose of 150 mg / week, a patient weighing less than 40 kg undergoing a same treatment may be administered a dose of 75 mg / week. As another example, in a treatment where patients that weigh 40 kg or more are administered a dose of 300 mg / month, a patient weighing less than 40 kg undergoing a same treatment may be administered a dose of 150 mg / month.

[0103] In certain embodiments, the frequency of about once per month may be a frequency of between once every 25 days and once every 32 days, between once every 28 days and once every 32 days, between once every 28 days and once every 31 days, about once every 28 days, about once every 29 days, about once every 30 days, or about once every 31 days.

[0104] The length of the treatment with administration of the TACI-Ig fusion molecule may be for at least 6 weeks, at least 12 weeks, at least 24 weeks, at least 36 weeks, at least 48 weeks, at least 52 weeks, at least 72 weeks, at least 96 weeks, at least 108 weeks, at least 3 years, at least 5 years, or at least 10 years. In some embodiments, the TACI-Ig fusion molecule may be administered chronically.

[0105] In some embodiments, the treatment with TACI-Ig fusion molecule is combined with stable supportive standard-of-care (SOC) therapy. Optionally, the supported SOC therapy may be a low-dose glucocorticoid (GCS) therapy (e.g., less than 10 mg / day prednisolone or equivalent) and / or calcineurin inhibitors (CNIs).

[0106] In some embodiments, the treatment with TACI-Ig fusion molecule is not combined with B -cell-directed biologic therapies, including but not limited to rituximab, obinutuzumab, and ofatumumab.

[0107] The formulation, dosage form, and route of administration of the TACI-Ig fusion molecule is not particularly limited, as long as it results in an appropriate serum concentration of the TACI-Ig fusion molecule that allows for the desired effects.27324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0108] Administration of a TACI-immunoglobulin protein to a subject can be intravenous, intraarterial, intraperitoneal, intramuscular, subcutaneous, intrapleural, intrathecal, by perfusion through a regional catheter, or by direct intralesional injection. When administering therapeutic proteins by injection, the administration may be by continuous infusion or by single or multiple boluses.

[0109] Additional routes of administration include oral, mucosal-membrane, pulmonary, and transcutaneous. Oral delivery is suitable for polyester microspheres, zein microspheres, proteinoid microspheres, polycyanoacrylate microspheres, and lipid- based systems. The feasibility of an intranasal delivery is exemplified by such a mode of insulin administration (see, for example, Hinchcliffe and Ilium, Adv. Drug Deliv. Rev. 35: 199 (1999)). Dry or liquid particles comprising TACI-immunoglobulin can be prepared and inhaled with the aid of dry-powder dispersers, liquid aerosol generators, or nebulizers (e.g., Pettit and Gombotz, TIBTECH 16:343 (1998); Patton et al., Adv. Drug Deliv. Rev. 35:235 (1999)). This approach is illustrated by the AERX diabetes management system, which is a hand-held electronic inhaler that delivers aerosolized insulin into the lungs. Studies have shown that proteins as large as 48,000 kDa have been delivered across skin at therapeutic concentrations with the aid of low-frequency ultrasound, which illustrates the feasibility of transcutaneous administration. Transdermal delivery using electroporation provides another means to administer a TACI-immunoglobulin protein.

[0110] A pharmaceutical composition comprising a TACI-immunoglobulin protein can be formulated according to known methods to prepare pharmaceutically useful compositions, whereby the therapeutic proteins are combined in a mixture with a pharmaceutically acceptable carrier. The term "pharmaceutically acceptable" designates that said carrier is a non-toxic, inert material that is compatible with the other ingredients of the pharmaceutical composition and not harmful to the patient that the pharmaceutical composition is administered to, such that it can be used in a pharmaceutical product. Substances suitable as carriers, diluents or excipients in pharmaceutical compositions are known to a skilled person in the art. Sterile phosphate-buffered saline is one example of a pharmaceutically acceptable carrier.[OHl] The pharmaceutical composition may further include e.g. additional adjuvants, antioxidants, buffering agents, bulking agents, colorants, emulsifiers, fillers, flavoring agents, preservatives, stabilizers, suspending agents and / or other customary pharmaceutical auxiliaries.28324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0112] For example, the TACI-Ig fusion molecule (e.g., atacicept) can be formulated as described in US Patent No. 8,637,021 (US Patent No. 8,637,021 is herewith incorporated by reference in its entirety).

[0113] The TACI-Ig fusion molecule (such as atacicept) may be administered in an aqueous solution containing, besides the TACI-Ig fusion molecule, trehalose (optionally 60 to 100 mg / ml) and an acetate buffer buffering the formulation at a pH ranging from 4.9-5.1 (see US Patent No. 8637021 B2 for details regarding formulation, which are incorporated herein by reference). The TACI-Ig fusion molecule may be included in said aqueous solution for example at a concentration of 25 to 150 mg TACI-Ig fusion molecule per ml of said aqueous solution. In some embodiments, a unit dosage strength for atacicept (per 1.0 ml) may be 150 mg.

[0114] A pharmaceutical composition comprising a TACI-immunoglobulin protein can be furnished in liquid form, in an aerosol, or in solid form. Liquid forms are illustrated by injectable solutions and oral suspensions. Exemplary solid forms include capsules, tablets, and controlled- release forms. The latter form is illustrated by mini-osmotic pumps and implants.

[0115] Liposomes provide one means to deliver therapeutic polypeptides to a subject intravenously, intraperitoneally, intrathecally, intramuscularly, subcutaneously, or via oral administration, inhalation, or intranasal administration. Liposomes are microscopic vesicles that consist of one or more lipid bilayers surrounding aqueous compartments. A variety of agents can be encapsulated in liposomes: hydrophobic agents partition in the bilayers and hydrophilic agents partition within the inner aqueous space(s). Moreover, it is possible to control the therapeutic availability of the encapsulated agent by varying liposome size, the number of bilayers, lipid composition, as well as the charge and surface characteristics of the liposomes. Other dosage forms can be devised by those skilled in the art.

[0116] As an illustration, pharmaceutical compositions may be supplied as a kit comprising a container that comprises a TACI-immunoglobulin protein. Therapeutic polypeptides can be provided in the form of an injectable solution for single or multiple doses, or as a sterile powder that will be reconstituted before injection. Alternatively, such a kit can include a dry-powder disperser, liquid aerosol generator, or nebulizer for administration of a therapeutic polypeptide. Such a kit may further comprise written information on indications and usage of the pharmaceutical composition. Moreover, such information may include a statement that the TACL29324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 immunoglobulin protein composition is contraindicated in patients with known hypersensitivity to either the TACI receptor moiety or the immunoglobulin moiety.Endpoints for treatment

[0117] A therapeutically effective amount and / or dosing of a TACI-Ig fusion molecule (e.g., atacicept) in treating a patient with B-cell responsive autoimmune glomerulopathy is expected to result in an improvement in kidney function, e.g., one or more of a reduction in proteinuria, a reduction in hematuria, or a maintenance or recovery of eGFR, and a reduction in one or more autoantibodies. As such, “treating” a B-cell responsive autoimmune glomerulopathy may include one or more of reducing proteinuria, reducing hematuria, maintaining eGFR, or reducing autoantibodies. There is therefore provided herein, in addition to methods of treating a B-cell responsive autoimmune glomerulopathy, methods of reducing proteinuria in a patient having a B- cell responsive autoimmune glomerulopathy, methods of reducing hematuria in a patient having a B-cell responsive autoimmune glomerulopathy, methods of maintaining eGFR in a patient having a B-cell responsive autoimmune glomerulopathy, and method of reducing autoantibodies in a patient having a B-cell responsive autoimmune glomerulopathy.

[0118] Relatedly, provided herein are TACI-immunoglobulin proteins, as described herein, for use in the treatment of a B-cell responsive autoimmune glomerulopathy, for use in reducing proteinuria in a patient having a B-cell responsive autoimmune glomerulopathy, for use in reducing hematuria in a patient having a B-cell responsive autoimmune glomerulopathy, for use in maintaining eGFR in a patient having a B-cell responsive autoimmune glomerulopathy, and for us in reducing autoantibodies in a patient having a B-cell responsive autoimmune glomerulopathy, as described herein with respect to the disclosed methods of treatment.

[0119] Similarly, in some embodiments are provided uses of the TACI-immunoglobulin proteins, as described herein, in the manufacture of medicaments for use in the treatment of a B- cell responsive autoimmune glomerulopathy, for use in reducing proteinuria in a patient having a B-cell responsive autoimmune glomerulopathy, for use in reducing hematuria in a patient having a B-cell responsive autoimmune glomerulopathy, for use in maintaining eGFR in a patient having a B-cell responsive autoimmune glomerulopathy, and for us in reducing autoantibodies in a patient having a B-cell responsive autoimmune glomerulopathy, as described herein with respect to the disclosed methods of treatment.30324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0120] In certain embodiments, proteinuria in the patient after treatment may be reduced by at least 10%, at least 20%, at least 25%, at least 30%, at least 35%, or at least 40% compared to the patient’s proteinuria before treatment. The comparison of proteinuria levels (e.g., urine protein concentration, UPCR, or UACR) before and after treatment may be based on natural log- transformed proteinuria levels. In cases where the proteinuria is determined based on a measure of mg protein / L urine, proteinuria of the patient may be reduced to 30 mg / L or less, which is considered to be indicative of disease remission, after treatment. In cases wherein the proteinuria is determined based on a weight ratio of urine protein: creatinine ratio (UPCR), the UPCR of the patient may be reduced to 0.5 mg urine / mg creatine or less, which is considered to be indicative of disease remission, after treatment.

[0121] The analysis of proteinuria may assess UPCR data determined from a urine specimen, e.g. a 24-hour urine specimens. UPCR analyses may be performed on natural log-transformed data. The relative change from baseline in UPCR may be analyzed using mixed-effects model for repeated measures (MMRM), where the response variable is natural log UPCR, and with fixed effects time (nominal visits in weeks) and baseline UPCR. Observed values and changes from baseline in UPCR may be summarized at nominal timepoints using descriptive statistics. For example, a geometric mean of percentage change derived from least-square means estimate and corresponding 95% confidence interval (CI) for each visit may be reported.

[0122] In certain embodiments, hematuria in the patient may cease (resolve) after treatment. In certain embodiments, the proportion of a patient population with hematuria may be reduced after treatment. In some embodiments, hematuria categories (negative / trace, 1+, 2+, or 3+) may be defined based on occult blood results from dipstick test. In some embodiments, hematuria resolution may be defined as hematuria improvement to negative / trace from >1+ at baseline.

[0123] Glomerulopathies may be progressive, so that the eGFR of a patient may continue to decrease over time. As such, in some cases, even maintenance of eGFR is considered to be a successful treatment. In certain embodiments, the eGFR in the patient after treatment is decreased by not more than 5%, not more than 6%, not more than 7%, not more than 8%, not more than 9%, or not more than 10% compared to before treatment. In certain embodiments, the eGFR in the patient after treatment is not decreased compared to before treatment. In certain embodiments, the eGFR in the patient after treatment is increased by about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% compared to before treatment. In certain embodiments, observed values 31324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 and changes from baseline in eGFR may be summarized at nominal timepoints using descriptive statistics. In certain embodiments, the change from baseline in eGFR will also be estimated by Mixed Model for Repeated Measures (MMRM) modeling. In certain embodiments, the eGFR in the patient after treatment is increased to at least 60 (ml / min / 1.73m2) or at least 90 ml / min / 1.73m2, which is considered to be indicative of disease remission.

[0124] As noted elsewhere herein, in some embodiments, a B-cell responsive autoimmune glomerulopathy may be characterized by a detectable presence in the patient of one or more autoantibodies to proteins expressed by kidney cells, e.g., podocytes, glomerular epithelial cells, and glomerular mesangial cells, as well as slit diaphragm proteins. In some embodiments, the proteins expressed by kidney cells are proteins expressed by glomerular mesangial cells. In some embodiments, the proteins expressed by kidney cells are slit diaphragm proteins. In some embodiments, the proteins expressed by kidney cells are proteins expressed by glomerular mesangial cells, or slit diaphragm proteins. In some embodiments, the one or more autoantibodies is an anti-PLA2R antibody, an anti-THSD7A antibody, or an anti-nephrin antibody. In some embodiments, reduction of the one or more autoantibodies, including reduction of the one or more autoantibodies to non-detectable levels, may be a measure of successful treatment. In certain embodiments, the autoantibodies in the patient after treatment may be reduced by at least 50%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% compared to before treatment. In certain embodiments, the autoantibodies in the patient after treatment may be reduced so that the autoantibodies are not detectable after the treatment. In some embodiments, the autoantibodies being not detectable corresponds to the autoantibodies having a titer of < 20 RU / ml, < 15 RU / ml, or < 10 RU / ml. In some embodiments, the autoantibody is assayed in a serum sample of the patient or in a kidney biopsy of the patient.Methods of patient evaluation using TACI-Ig fusion molecule

[0125] TACI-Ig fusion molecules may be used for evaluating a patient with a kidney disease or to determine a course of treatment for a patient with a kidney disease. TACI-Ig fusion molecules may also be used for selecting clinical trial candidates.

[0126] Provided herein are methods of characterizing glomerulopathies from a plurality of patients having kidney diseases. In certain embodiments, the method may comprise administering a TACI-Ig fusion molecule to the plurality of patients, assessing kidney function after a round of32324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 treatment, and selecting from the plurality of patients a patient that demonstrates improved kidney function after the round of treatment.

[0127] The plurality of patients may be determined to need treatment for a kidney disease based on, e.g., proteinuria, hematuria, or eGFR as described herein, or as otherwise identified by a clinician. A demonstration of improved kidney function after the round of treatment may be, for example, a reduction in proteinuria or hematuria, or maintenance of eGFR as described herein. The round of treatment may not require full recovery, but rather an indication that the TACI-Ig fusion molecule has an effect in improving kidney function, even minimally, as assessed by e.g., proteinuria, hematuria, or eGFR as described herein. As such, for patient evaluation purposes, the duration of treatment before assessment of kidney function may be relatively short, e.g., about 2 weeks, about 4 weeks, about 6 weeks, about 8 weeks, about 10 weeks, about 12 weeks, between 2 weeks and 4 weeks, between 2 weeks and 10 weeks, between 4 weeks and 10 weeks, between 6 weeks and 10 weeks, between 2 weeks and 12 weeks, between 4 weeks and 12 weeks, between 6 weeks and 12 weeks, between 8 weeks and 12 weeks, or between 10 weeks and 12 weeks.Depending on the patients, longer evaluation periods may also be employed.

[0128] In some embodiments, the selected patient may be designated as a patient that is receptive to treatment by a TACI-Ig fusion molecule, and receive further treatment with the same, or a different TACI-Ig fusion molecule, such as in accordance with the methods and uses described herein. In some embodiments, the selected patient may be a subject of further studies to detect autoantibodies in the subject, and to determine an autoantigen for the autoantibodies. See FIG. 4.

[0129] In some embodiments, after the patient with the improved kidney function is selected, a serum sample from the selected patient may be collected, assayed for detection of an autoantibody, and determination of an autoantigen of the autoantibody. The assay may be an immunological assay with a panel of suspected auto-antigens that may be expressed in kidney cells, but have not been previously established to play a role in kidney pathogenesis, with which binding of the autoantibodies detected in the serum sample is tested. The panel may include candidate autoantigens that are expressed by a kidney cell. The assay may be proteomic assay, e.g., two-dimensional gel electrophoresis (2 -DE), image analysis, or mass spectrometry (MS).33324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0130] Serum samples may be collected from multiple patients with improved kidney function after TACI-Ig fusion molecule treatment which may be assayed to detect autoantibodies from the serum samples and thereby determine the autoantigen for the autoantibodies. In some embodiments, where the autoantigen is a protein produced by a kidney cell, a B-cell responsive autoimmune glomerulopathy of a selected patient may be characterized based on the autoantigen.

[0131] In some embodiments, the selected patient may be designated as a clinical trial candidate, for e.g., B-cell responsive autoimmune glomerulopathy.

[0132] In some embodiments, the method may comprise collecting a serum sample from the clinical trial candidate, and assaying the serum sample for an autoantibody to determine the autoantigen of the autoantibody. The assay may be an immunological assay with a panel of autoantigens, optionally expressed by kidney cells, e.g., nephrin or THSD7A. The identity of the autoantigen may be used to select a clinical trial for the clinical trial candidate, then optionally have the clinical trial candidate participate in a selected clinical trial.

[0133] In certain embodiments, the autoantigen is a protein expressed by kidney cells, and the clinical trial candidate is designated as having a B-cell responsive autoimmune glomerulopathy. For example, if the autoantigen is determined to be nephrin, then the clinical trial candidate is designated as having an anti-nephrin glomerulopathy, and may be directed to participate in a clinical study for anti-nephrin glomerulopathy. In another example, if the autoantigen is determined to be THSD7A, then the clinical trial candidate is designated as having an anti- THSD7A glomerulopathy, and may be directed to participate in a clinical study for anti- THSD7A glomerulopathy.Sequences

[0134] SEQ ID NO: 1 (Amino acid sequence of fragment of TACI extracellular region included in Atacicept)AMRSCPEEQYWDPLLGTCMSCKTICNHQSQRTCAAFCRSLSCRKEQGKFYDHLLRDCISCAS IC GQHPKQCAYFCENKLRS

[0135] SEQ ID NO: 2 (Amino acid sequence of Ig region included in Atacicept)34324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431DKTHTCPPCPAPEAEGAPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPSS IEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0136] SEQ ID NO: 3 (Amino acid sequence of Atacicept)AMRSCPEEQYWDPLLGTCMSCKTICNHQSQRTCAAFCRSLSCRKEQGKFYDHLLRDCISCAS ICGQHPKQCAYFCENKLRSEPKSSDKTHTCPPCPAPEAEGAPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPSS IEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0137] SEQ ID NO: 4 (Amino acid sequence of a closely related TACI-Ig fusion protein to atacicept)SRVDQEERFPQGLWTGVAMRSCPEEQYWDPLLGTCMSCKTICNHQSQRTCAAFCRSLSCRKEQGKFYDHLLRDCISCAS ICGQHPKQCAYFCENKLRSPVNLPPELDKTHTCPPCPAPEAEGAPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPSS IEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN HYTQKSLSLSPGK

[0138] SEQ ID NO: 5 (Amino acid sequence of TACI-Ig fusion protein T1 of EP 2161287 Bl)SRVDQEERFPQGLWTGVAMRSCPEEQYWDPLLGTCMSCKTICNHQSQRTCAAFCRSLSCRKEQGKFYDHLLRDCISCAS ICGQHPKQCAYFCENKLDKPHTCPLCPAPELLGGPSVFLFPKPPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKATPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS PGK

[0139] SEQ ID NO: 6 (Amino acid sequence of TACI-Ig fusion protein T2 of EP 2161287 Bl)SRVDQEERFPQGLWTGVAMRSCPEEQYWDPLLGTCMSCKTICNHQSQRTCAAFCRSLSCRKEQGKFYDHLLRDCISCAS ICGQHPKQCAYFCENKLRSPVNLPPELDKPHTCPLCPAPELLGGPSVFL35324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431FPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKATPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN HYTQKSLSLSPGK

[0140] SEQ ID NO: 7 (Amino acid sequence of TACI-Ig fusion protein T3 of EP 2161287 Bl)SRVDQEERFPQGLWTGVAMRSCPEEQYWDPLLGTCMSCKTICNHQSQRTCAAFCRSLSCRCGQHPKQCAYFCENKLRSPVNLPPELGGGGGGGGGDKPHTCPLCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKATPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP GK

[0141] SEQ ID NO: 8 (Amino acid sequence of TACI-Ig fusion protein according to SEQ 4 of US 8193316 B2)SRVDQEERFPQGLWTGVAMRSCPEEQYWDPLLGTCMSCKTICNHQSQRTCAAFCRSLSCRKEQGKFYDHLLRDCISCAS ICGQHPKQCAYFCENKLRSPVNLPPELGGGGGGGGGDKPHTCPLCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKATPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK

[0142] SEQ ID NO: 9 (Amino acid sequence of TACI-Ig fusion protein T4 of EP 2161287 Bl)AMRSCPEEQYWDPLLGTCMSCKTICNHQSQRTCAAFCRSLSCRKEQGKFYDHLLRDCISCAS ICGQHPKQCAYFCENKLRSEPKSSDKPHTCPLCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKATPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0143] SEQ ID NO: 10: (Amino acid sequence of human TACI)MSGLGRSRRGGRSRVDQEERFPQGLWTGVAMRSCPEEQYWDPLLGTCMSCKTICNHQSQRTCAAFCRSLSCRKEQGKFYDHLLRDCISCAS ICGQHPKQCAYFCENKLRSPVNLPPELRRQRSGEVEN36324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431NSDNSGRYQGLEHRGSEASPALPGLKLSADQVALVYSTLGLCLCAVLCCFLVAVACFLKKRGDP CSCQPRSRPRQSPAKSSQDHAMEAGSPVSTSPEPVETCSFCFPECRAPTQESAVTPGTPDPTCA GRWGCHTRTTVLQPCPHIPDSGLGIVCVPAQEGGPGA

[0144] SEQ ID NO: 11 (Amino acid sequence of human TACI extracellular domain)MSGLGRSRRGGRSRVDQEERFPQGLWTGVAMRSCPEEQYWDPLLGTCMSCKTICNHQSQRTCAA FCRSLSCRKEQGKFYDHLLRDCISCAS ICGQHPKQCAYFCENKLRSPVNLPPELRRQRSGEVEN NSDNSGRYQGLEHRGSEASPALPGLKLSADQVALVYST

[0145] SEQ ID NO: 12 (Amino acid sequence of TACI-Ig fusion protein as provided in record EN2U82XV65 of Global Substance Registration System - GSRS)SLSCRKEQGEYYDHLLRDCISCAS ICGQHPKQCADFCENKLRSGSGGGGSEPKSSDKTHTCPPC PAPEAEGAPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGEnumerated Embodiments

[0146] The following non-limited enumerated embodiments are provided as exemplary.Set I

[0147] Embodiment 1-1. A method of treating a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain,37324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 wherein the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0148] Embodiment 1-2. A method of treating a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0149] Embodiment 1-3. A method of treating a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0150] Embodiment 1-4. A method of treating a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to: nephrin, THSD7A, CD2AP, Neurexin, Ephrin Bl, Nephi, Podocin, P-cadherin, FAT, ZO-1 or combinations thereof.

[0151] Embodiment 1-5. A method of treating a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept.

[0152] Embodiment 1-6. A method of treating a patient having an anti-THSD7A glomerulopathy, the method comprising administering to the patient in need thereof an effective38324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-THSD7A antibodies.

[0153] Embodiment 1-7. A method of treating a patient having an anti-THSD7A glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein the patient, prior to the administration of atacicept, has a detectable presence of anti-THSD7A antibodies.

[0154] Embodiment 1-8. A method of treating a patient having an anti-nephrin glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)- immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-nephrin antibodies.

[0155] Embodiment 1-9. A method of treating a patient having an anti-nephrin glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein the patient, prior to the administration of atacicept, has a detectable presence of anti-nephrin antibodies.

[0156] Embodiment I- 10. A method of reducing proteinuria in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, the method comprising administering to39324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 the patient an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: said administration reduces the amount of proteinuria compared to before the start of treatment.

[0157] Embodiment 1-11. A method of reducing proteinuria in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, the method comprising administering to the patient an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACL Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: said administration reduces the amount of proteinuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0158] Embodiment 1-12. A method of reducing proteinuria in a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: said administration reduces the amount of proteinuria compared to before the start of treatment, and40324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0159] Embodiment 1-13. A method of reducing proteinuria in a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: said administration reduces the amount of proteinuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0160] Embodiment 1-14. A method of reducing proteinuria in a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: said administration reduces the amount of proteinuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0161] Embodiment 1-15. A method of reducing proteinuria in a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein said administration reduces the amount of proteinuria compared to before the start of treatment.41324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0162] Embodiment 1-16. A method of reducing proteinuria in a patient having an anti- THSD7A glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand- interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: said administration reduces the amount of proteinuria compared to before the start of treatment, and the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-THSD7A antibodies.

[0163] Embodiment 1-17. A method of reducing proteinuria in a patient having an anti- THSD7A glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: said administration reduces the amount of proteinuria compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti- THSD7A antibodies.

[0164] Embodiment 1-18. A method of reducing proteinuria in a patient having an anti-nephrin glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein:42324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 said administration reduces the amount of proteinuria compared to before the start of treatment, and wherein the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-nephrin antibodies.

[0165] Embodiment 1-19. A method of reducing proteinuria in a patient having an anti-nephrin glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: said administration reduces the amount of proteinuria compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti- nephrin antibodies.

[0166] Embodiment 1-20. A method of reducing hematuria in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, the method comprising administering to the patient an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand- interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein said administration reduces the amount of hematuria compared to before the start of treatment.

[0167] Embodiment 1-21. A method of reducing hematuria in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, the method comprising administering to the patient an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand- interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:43324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: said administration reduces the amount of hematuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0168] Embodiment 1-22. A method of reducing hematuria in a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: said administration reduces the amount of hematuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0169] Embodiment 1-23. A method of reducing hematuria in a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACL Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: said administration reduces the amount of hematuria compared to before the start of treatment, and44324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0170] Embodiment 1-24. A method of reducing hematuria in a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: said administration reduces the amount of hematuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0171] Embodiment 1-25. A method of reducing hematuria in a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein said administration reduces the amount of hematuria compared to before the start of treatment.

[0172] Embodiment 1-26. A method of reducing hematuria in a patient having an anti- THSD7A glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand- interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: said administration reduces the amount of hematuria compared to before the start of treatment, and the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-THSD7A antibodies.45324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0173] Embodiment 1-27. A method of reducing hematuria in a patient having an anti- THSD7A glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: said administration reduces the amount of hematuria compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti- THSD7A antibodies.

[0174] Embodiment 1-28. A method of reducing hematuria in a patient having an anti-nephrin glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: said administration reduces the amount of hematuria compared to before the start of treatment, and wherein the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-nephrin antibodies.

[0175] Embodiment 1-29. A method of reducing hematuria in a patient having an anti-nephrin glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: said administration reduces the amount of hematuria compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti- nephrin antibodies.46324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0176] Embodiment 1-30. A method of maintaining EGFR in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, the method comprising administering to the patient an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand- interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein said administration at least maintains a measure of EGFR compared to before the start of treatment.

[0177] Embodiment 1-31. A method of maintaining EGFR in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, the method comprising administering to the patient an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand- interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: said administration at least maintains a measure of EGFR compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0178] Embodiment 1-32. A method of maintaining EGFR in a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein:47324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 said administration at least maintains a measure of EGFR compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0179] Embodiment 1-33. A method of maintaining EGFR in a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: said administration at least maintains a measure of EGFR compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0180] Embodiment 1-34. A method of maintaining EGFR in a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: said administration at least maintains a measure of EGFR compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to: nephrin or THSD7A.

[0181] Embodiment 1-35. A method of maintaining EGFR in a patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in48324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 need thereof an effective amount of atacicept, wherein said administration at least maintains a measure of EGFR compared to before the start of treatment.

[0182] Embodiment 1-36. A method of maintaining EGFR in a patient having an anti-THSD7A glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: said administration at least maintains a measure of EGFR compared to before the start of treatment, and the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti- THSD7A antibodies.

[0183] Embodiment 1-37. A method of maintaining EGFR in a patient having an anti-THSD7A glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: said administration at least maintains a measure of EGFR compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti- THSD7A antibodies.

[0184] Embodiment 1-38. A method of maintaining EGFR in a patient having an anti-nephrin glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and49324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431(ii) a human immunoglobulin-constant domain, wherein: said administration at least maintains a measure of EGFR compared to before the start of treatment, and wherein the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-nephrin antibodies.

[0185] Embodiment 1-39. A method of maintaining EGFR in a patient having an anti-nephrin glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: said administration at least maintains a measure of EGFR compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti- nephrin antibodies.

[0186] Embodiment 1-40. A method of reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy in a patient in need thereof, the method comprising administering to the patient an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: said administration reduces the amount of the one or more autoantibodies in the patient compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.50324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0187] Embodiment 1-41. A method of reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: said administration reduces the amount of the one or more autoantibodies in the patient compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0188] Embodiment 1-42. A method of reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: said administration reduces the amount of the one or more autoantibodies in the patient compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0189] Embodiment 1-43. A method of reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: said administration reduces the amount of the one or more autoantibodies in the patient compared to before the start of treatment, and51324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to: nephrin or THSD7A.

[0190] Embodiment 1-44. A method of reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein said administration reduces the amount of the one or more autoantibodies in the patient compared to before the start of treatment.

[0191] Embodiment 1-45. A method of reducing anti-THSD7A antibodies in a patient having an anti-THSD7A glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-THSD7A antibodies, and said administration reduces the amount of the anti-THSD7A antibodies in the patient compared to before the start of treatment.

[0192] Embodiment 1-46. A method of reducing anti-THSD7A antibodies in a patient having an anti-THSD7A glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: the patient, prior to the administration of atacicept, has a detectable presence of anti- THSD7A antibodies, and said administration reduces the amount of the anti-THSD7A antibodies in the patient compared to before the start of treatment.52324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0193] Embodiment 1-47. A method for reducing anti-nephrin antibodies in a patient having an anti-nephrin glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand- interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein: wherein the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-nephrin antibodies, and said administration reduces the amount of the anti-nephrin antibodies compared to before the start of treatment.

[0194] Embodiment 1-48. A method of reducing anti-nephrin antibodies in a patient having an anti-nephrin glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of atacicept, wherein: the patient, prior to the administration of atacicept, has a detectable presence of anti- nephrin antibodies, and said administration reduces the amount of the anti-nephrin antibodies compared to before the start of treatment.

[0195] Embodiment 1-49. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain,53324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 for use in treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0196] Embodiment 1-50. An atacicept for use in treating patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0197] Embodiment 1-51. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0198] Embodiment 1-52. An atacicept for use in treating a patient having a B-cell responsive autoimmune glomerulopathy, wherein the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0199] Embodiment 1-53. An atacicept for use in treating a patient having a B-cell responsive autoimmune glomerulopathy.

[0200] Embodiment 1-54. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:54324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in treating a patient having an anti-THSD7A glomerulopathy in need thereof, wherein the patient, prior to the treatment with the TACI-Ig fusion molecule, has a detectable presence of anti-THSD7A antibodies.

[0201] Embodiment 1-55. An atacicept for use in treating a patient having an anti-THSD7A glomerulopathy in need thereof, wherein the patient, prior to the treatment with atacicept, has a detectable presence of anti-THSD7A antibodies.

[0202] Embodiment 1-56. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in treating a patient having an anti-nephrin glomerulopathy in need thereof, wherein the patient, prior to the treatment with the TACI-Ig fusion molecule, has a detectable presence of anti-nephrin antibodies.

[0203] Embodiment 1-57. An atacicept for use in treating a patient having an anti-nephrin glomerulopathy, wherein the patient, prior to the treatment with atacicept, has a detectable presence of anti-nephrin antibodies.

[0204] Embodiment 1-58. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and55324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431(ii) a human immunoglobulin-constant domain, for use in reducing proteinuria in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of proteinuria compared to before the start of treatment.

[0205] Embodiment 1-59. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in reducing proteinuria in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of proteinuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0206] Embodiment 1-60. An atacicept for use in reducing proteinuria in a patient having a B- cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of proteinuria compared to before the start of treatment, and the B- cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0207] Embodiment 1-61. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and56324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431(ii) a human immunoglobulin-constant domain, for use in reducing proteinuria in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of proteinuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0208] Embodiment 1-62. An atacicept for use in reducing proteinuria in a patient having a B- cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of proteinuria compared to before the start of treatment, and the B- cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0209] Embodiment 1-63. An atacicept for use in reducing proteinuria in a patient having a B- cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of proteinuria compared to before the start of treatment.

[0210] Embodiment 1-64. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in reducing proteinuria in a patient in need thereof having an anti-THSD7A glomerulopathy, wherein an administration of said TACI-Ig fusion molecule reduces the amount of proteinuria compared to before the start of treatment, and the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-THSD7A antibodies.

[0211] Embodiment 1-65. An atacicept for use in reducing proteinuria in a patient having an anti-THSD7A glomerulopathy in need thereof, wherein an administration of said atacicept57324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 reduces the amount of proteinuria compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti-THSD7A antibodies.

[0212] Embodiment 1-66. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in reducing proteinuria in a patient in need thereof having an anti-nephrin glomerulopathy, wherein an administration of said TACI-Ig fusion molecule reduces the amount of proteinuria compared to before the start of treatment, and wherein the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-nephrin antibodies.

[0213] Embodiment 1-67. An atacicept for use in reducing proteinuria in a patient having an anti-nephrin glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of proteinuria compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti-nephrin antibodies.

[0214] Embodiment 1-68. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in reducing hematuria in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of hematuria compared to before the start of treatment.58324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0215] Embodiment 1-69. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in reducing hematuria in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of hematuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0216] Embodiment 1-70. An atacicept for use in reducing hematuria in a patient having a B- cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of hematuria compared to before the start of treatment, and the B- cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0217] Embodiment 1-71. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in reducing hematuria in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of hematuria compared to before the start of treatment, and the B-cell59324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0218] Embodiment 1-72. An atacicept for use in reducing hematuria in a patient having a B- cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of hematuria compared to before the start of treatment, and the B- cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0219] Embodiment 1-73. An atacicept for use in reducing hematuria in a patient having a B- cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of hematuria compared to before the start of treatment.

[0220] Embodiment 1-74. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in reducing hematuria in a patient having an anti-THSD7A glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of hematuria compared to before the start of treatment, and the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-THSD7A antibodies.

[0221] Embodiment 1-75. An atacicept for use in reducing hematuria in a patient having an anti-THSD7A glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of hematuria compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti-THSD7A antibodies.

[0222] Embodiment 1-76. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:60324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in reducing hematuria in a patient having an anti-nephrin glomerulopathy in need thereof, wherein an administration of said TACLIg fusion molecule reduces the amount of hematuria compared to before the start of treatment, and wherein the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-nephrin antibodies.

[0223] Embodiment 1-77. An atacicept for use in reducing hematuria in a patient having an anti-nephrin glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of hematuria compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti-nephrin antibodies.

[0224] Embodiment 1-78. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in maintaining EGFR in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule at least maintains a measure of EGFR compared to before the start of treatment.

[0225] Embodiment 1-79. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and61324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431(ii) a human immunoglobulin-constant domain, for use in maintaining EGFR in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule at least maintains a measure of EGFR compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0226] Embodiment 1-80. A atacicept for use in maintaining EGFR in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept at least maintains a measure of EGFR compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0227] Embodiment 1-81. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in maintaining EGFR in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule at least maintains a measure of EGFR compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0228] Embodiment 1-82. An atacicept for use in maintaining EGFR in a patient having a B- cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept at least maintains a measure of EGFR compared to before the start of treatment, and the62324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to: nephrin or THSD7A.

[0229] Embodiment 1-83. An atacicept for use in maintaining EGFR in a patient having a B- cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept at least maintains a measure of EGFR compared to before the start of treatment.

[0230] Embodiment 1-84. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in maintaining EGFR in a patient having an anti-THSD7A glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule at least maintains a measure of EGFR compared to before the start of treatment, and the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti- THSD7A antibodies.

[0231] Embodiment 1-85. An atacicept for use in maintaining EGFR in a patient having an anti-THSD7A glomerulopathy in need thereof, wherein an administration of said atacicept at least maintains a measure of EGFR compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti-THSD7A antibodies.

[0232] Embodiment 1-86. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain,63324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 for use in maintaining EGFR in a patient having an anti-nephrin glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule at least maintains a measure of EGFR compared to before the start of treatment, and wherein the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-nephrin antibodies.

[0233] Embodiment 1-87. An atacicept for use in maintaining EGFR in a patient having an anti-nephrin glomerulopathy in need thereof, wherein an administration of said atacicept at least maintains a measure of EGFR compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti-nephrin antibodies.

[0234] Embodiment 1-88. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy in a patient in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of the one or more autoantibodies in the patient compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0235] Embodiment 1-89. An atacicept for use in reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy in a patient in need thereof, wherein an administration of said atacicept reduces the amount of the one or more autoantibodies in the patient compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.64324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0236] Embodiment 1-90. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy in a patient in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of the one or more autoantibodies in the patient compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0237] Embodiment 1-91. An atacicept for use in reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy in a patient in need thereof, wherein an administration of said atacicept reduces the amount of the one or more autoantibodies in the patient compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to: nephrin or THSD7A.

[0238] Embodiment 1-92. An atacicept for use in reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy in a patient in need thereof, wherein an administration of said atacicept reduces the amount of the one of more autoantibodies in the patient compared to before the start of treatment.

[0239] Embodiment 1-93. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain,65324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 for use in reducing anti-THSD7A antibodies in a patient having an anti-THSD7A glomerulopathy in need thereof, wherein the patient, prior to an administration of the TACI-Ig fusion molecule, has a detectable presence of anti-THSD7A antibodies, and said administration reduces the amount of the anti-THSD7A antibodies in the patient compared to before the start of treatment.

[0240] Embodiment 1-94. An atacicept for use in reducing anti-THSD7A antibodies in a patient having an anti-THSD7A glomerulopathy in need thereof, wherein the patient, prior to an administration of atacicept, has a detectable presence of anti-THSD7A antibodies, and said administration reduces the amount of the anti-THSD7A antibodies in the patient compared to before the start of treatment.

[0241] Embodiment 1-95. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in reducing anti-nephrin antibodies in a patient having an anti-nephrin glomerulopathy in need thereof, wherein the patient, prior to an administration of the TACI-Ig fusion molecule, has a detectable presence of anti-nephrin antibodies, and said administration reduces the amount of the anti-nephrin antibodies compared to before the start of treatment.

[0242] Embodiment 1-96. An atacicept for use in reducing anti-nephrin antibodies in a patient having an anti-nephrin glomerulopathy in need thereof, wherein the patient, prior to an administration of atacicept, has a detectable presence of anti-nephrin antibodies, and said administration reduces the amount of the anti-nephrin antibodies compared to before the start of treatment.

[0243] Embodiment 1-97. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:66324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0244] Embodiment 1-98. Use of an atacicept in the manufacture of a medicament for treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the B- cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0245] Embodiment 1-99. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACL Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0246] Embodiment I- 100. Use of an atacicept in the manufacture of a medicament for treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the B- cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.67324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0247] Embodiment 1-101. Use of an atacicept in the manufacture of a medicament for treating a patient in need thereof having a B-cell responsive autoimmune glomerulopathy.

[0248] Embodiment 1-102. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for treating a patient having an anti-THSD7A glomerulopathy in need thereof, wherein the patient, prior to an administration of the TACLIg fusion molecule, has a detectable presence of anti-THSD7A antibodies.

[0249] Embodiment 1-103. Use of an atacicept in the manufacture of a medicament for treating a patient having an anti-THSD7A glomerulopathy, wherein the patient, prior to an administration of atacicept, has a detectable presence of anti-THSD7A antibodies.

[0250] Embodiment 1-104. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACL Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for treating a patient having an anti-nephrin glomerulopathy in need thereof, wherein the patient, prior to an administration of the TACLIg fusion molecule, has a detectable presence of anti-nephrin antibodies.

[0251] Embodiment 1-105. Use of an atacicept in the manufacture of a medicament for treating a patient having an anti-nephrin glomerulopathy in need thereof, wherein the patient, prior to an administration of atacicept, has a detectable presence of anti-nephrin antibodies.68324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0252] Embodiment 1-106. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for reducing proteinuria in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of proteinuria compared to before the start of treatment.

[0253] Embodiment 1-107. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for reducing proteinuria in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of proteinuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0254] Embodiment 1-108. Use of an atacicept in the manufacture of a medicament for reducing proteinuria in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of proteinuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.69324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0255] Embodiment 1-109. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for reducing proteinuria in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of proteinuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0256] Embodiment 1-110. Use of an atacicept in the manufacture of a medicament for reducing proteinuria in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of proteinuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0257] Embodiment 1-111. Use of an atacicept in the manufacture of a medicament for reducing proteinuria in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of proteinuria compared to before the start of treatment.

[0258] Embodiment 1-112. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain,70324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 in the manufacture of a medicament for reducing proteinuria in a patient having an anti- THSD7A glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of proteinuria compared to before the start of treatment, and the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-THSD7A antibodies.

[0259] Embodiment 1-113. Use of an atacicept in the manufacture of a medicament for reducing proteinuria in a patient having an anti-THSD7A glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of proteinuria compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti-THSD7A antibodies.

[0260] Embodiment 1-114. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for reducing proteinuria in a patient in need thereof having an anti-nephrin glomerulopathy, wherein an administration of said TACI-Ig fusion molecule reduces the amount of proteinuria compared to before the start of treatment, and wherein the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-nephrin antibodies.

[0261] Embodiment 1-115. Use of an atacicept in the manufacture of a medicament for reducing proteinuria in a patient having an anti-nephrin glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of proteinuria compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti-nephrin antibodies.71324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0262] Embodiment 1-116. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for reducing hematuria in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of hematuria compared to before the start of treatment.

[0263] Embodiment 1-117. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for reducing hematuria in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of hematuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0264] Embodiment 1-118. Use of an atacicept in the manufacture of a medicament for reducing hematuria in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of hematuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.72324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0265] Embodiment 1-119. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for reducing hematuria in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of hematuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0266] Embodiment 1-120. Use of an atacicept in the manufacture of a medicament for reducing hematuria in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of hematuria compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0267] Embodiment 1-121. Use of an atacicept in the manufacture of a medicament for reducing hematuria in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of hematuria compared to before the start of treatment.

[0268] Embodiment 1-122. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain,73324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 in the manufacture of a medicament for reducing hematuria in a patient having an anti- THSD7A glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of hematuria compared to before the start of treatment, and the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-THSD7A antibodies.

[0269] Embodiment 1-123. Use of an atacicept in the manufacture of a medicament for reducing hematuria in a patient having an anti-THSD7A glomerulopathy in need thereof, wherein an administration of said atacicept reduces the amount of hematuria compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti-THSD7A antibodies.

[0270] Embodiment 1-124. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for reducing hematuria in a patient having an anti- nephrin glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule reduces the amount of hematuria compared to before the start of treatment, and wherein the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-nephrin antibodies.

[0271] Embodiment 1-125. Use of an atacicept in the manufacture of a medicament for reducing hematuria in a patient having an anti-nephrin glomerulopathy, wherein an administration of said atacicept reduces the amount of hematuria compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti-nephrin antibodies.74324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0272] Embodiment 1-126. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for maintaining EGFR in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule at least maintains a measure of EGFR compared to before the start of treatment.

[0273] Embodiment 1-127. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for maintaining EGFR in a patient with a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule at least maintains a measure of EGFR compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0274] Embodiment 1-128. Use of an atacicept in the manufacture of a medicament for maintaining EGFR in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept at least maintains a measure of EGFR compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.75324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0275] Embodiment 1-129. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for maintaining EGFR in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule at least maintains a measure of EGFR compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0276] Embodiment 1-130. Use of an atacicept in the manufacture of a medicament for maintaining EGFR in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept at least maintains a measure of EGFR compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to: nephrin or THSD7A.

[0277] Embodiment 1-131. Use of an atacicept in the manufacture of a medicament for maintaining EGFR in a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein an administration of said atacicept at least maintains a measure of EGFR compared to before the start of treatment.

[0278] Embodiment 1-132. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain,76324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 in the manufacture of a medicament for maintaining EGFR in a patient having an anti- THSD7A glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule at least maintains a measure of EGFR compared to before the start of treatment, and the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti- THSD7A antibodies.

[0279] Embodiment 1-133. Use of an atacicept in the manufacture of a medicament for maintaining EGFR in a patient having an anti-THSD7A glomerulopathy in need thereof, wherein an administration of said atacicept at least maintains a measure of EGFR compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti-THSD7A antibodies.

[0280] Embodiment 1-134. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for maintaining EGFR in a patient having an anti- nephrin glomerulopathy in need thereof, wherein an administration of said TACI-Ig fusion molecule at least maintains a measure of EGFR compared to before the start of treatment, and wherein the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-nephrin antibodies.

[0281] Embodiment 1-135. Use of an atacicept in the manufacture of a medicament for maintaining EGFR in a patient having an anti-nephrin glomerulopathy in need thereof, wherein an administration of said atacicept at least maintains a measure of EGFR compared to before the start of treatment, and the patient, prior to the administration of atacicept, has a detectable presence of anti-nephrin antibodies.77324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0282] Embodiment 1-136. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BLyS (B Lymphocyte Stimulator) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy in a patient in need thereof, wherein an administration of said TACLIg fusion molecule reduces the amount of the one or more autoantibodies in the patient compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0283] Embodiment 1-137. Use of an atacicept in the manufacture of a medicament for reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy in a patient in need thereof, wherein an administration of said atacicept reduces the amount of the one or more autoantibodies in the patient compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of one or more autoantibodies to a slit diaphragm protein, or to a protein expressed by glomerular mesangial cells.

[0284] Embodiment 1-138. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACL Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy in a patient in need thereof, wherein an78324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 administration of said TACI-Ig fusion molecule reduces the amount of the one or more autoantibodies in the patient compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin or THSD7A.

[0285] Embodiment 1-139. Use of an atacicept in the manufacture of a medicament for reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy in a patient in need thereof, wherein an administration of said atacicept reduces the amount of the one or more autoantibodies in the patient compared to before the start of treatment, and the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to: nephrin or THSD7A.

[0286] Embodiment 1-140. Use of an atacicept in the manufacture of a medicament for reducing one or more autoantibodies associated with a B-cell responsive autoimmune glomerulopathy in a patient in need thereof, wherein an administration of said atacicept reduces the amount of the one or more autoantibodies in the patient compared to before the start of treatment.

[0287] Embodiment 1-141. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for reducing anti-THSD7A antibodies in a patient having an anti-THSD7A glomerulopathy in need thereof, wherein the patient, prior to the administration of the TACI-Ig fusion molecule, has a detectable presence of anti-THSD7A antibodies, and an administration of said TACI-Ig fusion molecule reduces the amount of the anti-THSD7A antibodies in the patient compared to before the start of treatment.

[0288] Embodiment 1-142. Use of an atacicept in the manufacture of a medicament for reducing anti-THSD7A antibodies in a patient having an anti-THSD7A glomerulopathy in need79324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 thereof, wherein the patient, prior to the administration of atacicept, has a detectable presence of anti-THSD7A antibodies, and an administration of said atacicept reduces the amount of the anti- THSD7A antibodies in the patient compared to before the start of treatment.

[0289] Embodiment 1-143. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI- Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for reducing anti-nephrin antibodies in a patient having an anti-nephrin glomerulopathy in need thereof, wherein the patient, prior to an administration of the TACI-Ig fusion molecule, has a detectable presence of anti-nephrin antibodies, and said administration reduces the amount of the anti-nephrin antibodies compared to before the start of treatment.

[0290] Embodiment 1-144. Use of an atacicept in the manufacture of a medicament for reducing anti-nephrin antibodies in a patient having an anti-nephrin glomerulopathy in need thereof, wherein the patient, prior to the administration of atacicept, has a detectable presence of anti-nephrin antibodies, and an administration of said atacicept reduces the amount of the anti- nephrin antibodies compared to before the start of treatment.

[0291] Embodiment 1-145. The method of any one of embodiments 1-1, 1-2, 1-11, 1-12, 1-21, 1- 22, 1-31, 1-32, 1-40, and 1-41, the TACI-Ig fusion molecule or atacicept of any one of embodiments 1-49, 1-50, 1-59, 1-60, 1-69, 1-70, 1-79, 1-80, 1-88, and 1-89, or the use according to any one of embodiments 1-97, 1-98, 1-107, 1-108, 1-117, 1-118, 1-127, 1-128, 1-136, and 1-137, wherein the one or more autoantibodies to a slit diaphragm protein are: anti-nephrin antibodies or anti-THSD7A antibodies.

[0292] Embodiment 1-146. The method, the TACI-Ig fusion molecule or atacicept, or the use according to embodiment 1-145, wherein the one or more autoantibodies are anti-THSD7A80324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 antibodies, and the B-cell responsive autoimmune glomerulopathy is primary membranous nephropathy (pMN).

[0293] Embodiment 1-147. The method, the TACI-Ig fusion molecule or atacicept, or the use according to embodiment 1-145, wherein the one or more autoantibodies are an anti-nephrin antibodies, and the B-cell responsive autoimmune glomerulopathy is primary minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS).

[0294] Embodiment 1-148. The method of any one of embodiments 1-5, 1- 10, 1-15, 1-20, 1-25, 1-30. 1-35, and 1-44, the TACI-Ig fusion molecule or atacicept of any one of embodiments 1-53, 1-58. 1-63, 1-68, 1-73, 1-78, 1-83, and 1-92 , or the use according to any one of embodiments I- 101 , 1-106. 1- 111, 1- 116, 1-121, 1-126, 1-131, and 1-140, wherein the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to: PLA2R, nephrin, or THSD7A.

[0295] Embodiment 1-149. The method of embodiment 1-148, the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to PLA2R or THSD7A, and the B-cell responsive autoimmune glomerulopathy is primary membranous nephropathy (pMN).

[0296] Embodiment 1-150. The method, the TACI-Ig fusion molecule or atacicept, or the use according to embodiment 1-148, the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence in the patient of autoantibodies to nephrin, and the B-cell responsive autoimmune glomerulopathy is primary minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS).

[0297] Embodiment 1-151. The method of any one of embodiments 1-1 to 1-4, 1- 10 to 1-14, 1-21 to 1-24, 1-31 to 1-34, 1-40 to 1-43, 1-45 to 1-48 and 1-148 to 1-150, the TACI-Ig fusion molecule or atacicept of any one of embodiments 1-49 to 1-52, 1-58 to 1-62, 1-69 to 1-72, 1-79 to 1-82, 1-88 to I-91. 1-93 to 1-96 and 1-148 to 1-150, or the use according to any one of embodiments 1-97 to 1-100, 1-106 to 1-110, 1-117 to 1-120, 1-127 to 1-130, 1-136 to 1-139, 1-141 to 1-144 and 1-148 to 1-150, wherein the detectable presence in the patient is a detectable presence in a serum sample of the patient.81324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0298] Embodiment 1-152. The method of any one of embodiments 1-1 to 1-4, 1- 10 to 1-14, 1-21 to 1-24, 1-31 to 1-34, 1-40 to 1-43, and 1-148 to 1-150, the TACI-Ig fusion molecule or atacicept of any one of embodiments 1-49 to 1-52, 1-58 to 1-62, 1-69 to 1-72, 1-79 to 1-82, 1-88 to 1-91 and 1-148 to 1-150, or the use according to any one of embodiments 1-97 to 1-100, 1-106 to 1-110, 1-117 to I-120. 1-127 to 1-130, 1-136 to 1-139 and 1-148 to 1-150, wherein the detectable presence in the patient is a detectable presence in a kidney biopsy of the patient.

[0299] Embodiment 1-153. The method of any one of embodiments 1-40 to 1-44, the TACI-Ig fusion molecule or atacicept of any one of embodiments 1-88 to 1-92, or the use according to any one of embodiments 1-136 to 1-140, wherein the administration reduces the amount of the one or more autoantibodies in the patient by about at least 50% compared to before the start of treatment.

[0300] Embodiment 1-154. The method of any one of embodiments 1-40 to 1-44, the TACI-Ig fusion molecule or atacicept of any one of embodiments 1-88 to 1-92, or the use according to any one of embodiments 1-136 to 1-140, wherein the one or more autoantibodies become undetectable in the patient after the administration.

[0301] Embodiment 1-155. The method of any one of embodiments 1-6, 1-7, 1-16, 1-17, 1-26, 1-27. 1-36, 1-37, 1-45, and 1-46, the TACI-Ig fusion molecule or atacicept of any one of embodiments 1-54, 1-55, 1-64, 1-65, 1-74, 1-75, 1-84, 1-85, 1-93, and 1-94, or the use according to any one of embodiments 1-102, 1-103, 1-112, 1-113, 1-122, 1-123, 1-132, 1-133, 1-141, and 1-142 wherein the anti-THSD7A glomerulopathy is membranous nephropathy (MN).

[0302] Embodiment 1-156. The method of any one of embodiments 1-8, 1-9, 1-18, 1-19, 1-28, 1-29. 1-38, 1-39, 1-47, and 1-48, the TACI-Ig fusion molecule or atacicept of any one of embodiments 1-56, 1-57, 1-66, 1-67, 1-76, 1-77, 1-86, 1-87, 1-95, and 1-96, or the use according to any one of embodiments 1-104, 1-105, 1-114, 1-115, 1-124, 1-125, 1-134, 1-135, 1-143, and I- 144, wherein the anti-nephrin glomerulopathy is minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS).

[0303] Embodiment 1-157. The method of any one of embodiments 1-1 to 1-9, the TACI-Ig fusion molecule or atacicept of any one of embodiments 1-49 to 1-57, or the use according to any one of embodiments 1-97 to 1-105, wherein the treating is selected from the group consisting of:82324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 reducing proteinuria, reducing hematuria, maintaining EGFR, and reducing one or more autoantibodies.

[0304] Embodiment 1-158. The method, the TACI-Ig fusion molecule or atacicept, or the use according to embodiment 1-157, wherein the treating is reducing proteinuria.

[0305] Embodiment 1-159. The method, the TACI-Ig fusion molecule or atacicept, or the use according to embodiment 1-157, wherein the treating is reducing hematuria.

[0306] Embodiment 1-160. The method, the TACI-Ig fusion molecule or atacicept, or the use according to embodiment 1-157, wherein the treating is maintaining EGFR.

[0307] Embodiment 1-161. The method, the TACI-Ig fusion molecule or atacicept, or the use according to embodiment 1-157, wherein the treating is reducing the one or more autoantibodies.

[0308] Embodiment 1-162. The method of any one of embodiments I- 10 to 1-19 and 1-157 to I- 158, the TACI-Ig fusion molecule or atacicept according to any one of embodiments 1-58 to 1-67 and 1-157 to 1-158, or the use according to any one of embodiments 1-106 to 1-115 and 1-157 to I- 158, wherein the proteinuria is reduced by at least 10%, at least 20%, at least 25%, at least 30%, at least 35%, or at least 40% compared to before treatment.

[0309] Embodiment 1-163. The method of any one of embodiments I- 10 to 1-19 and 1-157 to I- 158, the TACI-Ig fusion molecule or atacicept according to any one of embodiments 1-58 to 1-67 and 1-157 to 1-158, or the use according to any one of embodiments 1-106 to 1-115 and 1-157 to I- 158, wherein the proteinuria is determined based on a measure of mg protein / L urine.

[0310] Embodiment 1-164. The method, the TACI-Ig fusion molecule or atacicept, or the use according to embodiment 1-163, wherein the mg protein / L urine of the patient is reduced to 30 mg / L or less after treatment.

[0311] Embodiment 1-165. The method of any one of embodiments I- 10 to 1-19, and 1-157 to I- 158, the TACI-Ig fusion molecule or atacicept according to any one of embodiments 1-58 to 1-67, and 1-157 to 1-158, or the use according to any one of embodiments 1-106 to 1-115, and 1-157 to I- 158, wherein the proteinuria is determined based on a weight ratio of urine protein : creatinine ratio (UPCR).83324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0312] Embodiment 1-166. The method, the TACI-Ig fusion molecule or atacicept, or the use according to embodiment 1-165, wherein the UPCR of the patient is reduced to 0.5 mg urine / mg creatine or less after treatment.

[0313] Embodiment 1-167. The method of any one of embodiments 1-21 to 1-29 and 1-159, the TACI-Ig fusion molecule or atacicept according to any one of embodiments 1-69 to 1-77 and I-159, or the use according to any one of embodiments 1-117 to 1-125 and 1-159, wherein the hematuria ceases in the patient.

[0314] Embodiment 1-168. The method of any one of embodiments 1-31 to 1-39 and 1-160, the TACI-Ig fusion molecule or atacicept according to any one of embodiments 1-79 to 1-87 and I-160, or the use according to any one of embodiments 1-127 to 1-135 and 1-160, wherein the eGFR is decreased by not more than 5% or not more than 10% compared to before treatment.

[0315] Embodiment 1-169. The method of any one of embodiments 1-31 to 1-39 and 1-160, the TACI-Ig fusion molecule or atacicept according to any one of embodiments 1-79 to 1-87 and I- 160, or the use according to any one of embodiments 1-127 to 1-135 and 1-160, wherein the eGFR is not decreased compared to before treatment.

[0316] Embodiment 1-170. The method of any one of embodiments 1-31 to 1-39 and 1-160, the TACI-Ig fusion molecule or atacicept according to any one of embodiments 1-79 to 1-87 and I- 160, or the use according to any one of embodiments 1-127 to 1-135 and 1-160, wherein the eGFR is increased by about 5% or about 10% compared to before treatment.

[0317] Embodiment 1-171. The method of any one of embodiments 1-31 to 1-39 and 1-160, the TACI-Ig fusion molecule or atacicept according to any one of embodiments 1-79 to 1-87 and I-160, or the use according to any one of embodiments 1-127 to 1-135 and 1-160, wherein the eGFR is increased to at least 60 milliliters per minute per 1.73 square meters of body surface area (ml / min / 1.73m2) or at least 90 ml / min / 1.73m2.

[0318] Embodiment 1-172. The method of any one of embodiments 1-40 to 1-44 and 1-161, the TACI-Ig fusion molecule or atacicept according to any one of embodiments 1-88 to 1-92 and I-161, or the use according to any one of embodiments 1-136 to 1-140 and 1-161, wherein the one or more autoantibodies are reduced by at least 50%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% compared to before treatment.84324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0319] Embodiment 1-173. The method, the TACI-Ig fusion molecule or atacicept, or the use according to embodiment 1-172, wherein the one or more autoantibodies are not detectable after the treatment.

[0320] Embodiment 1-174. The method of embodiment 1-45 or 1-46, the TACI-Ig fusion molecule or atacicept according to embodiment 1-93 or 1-94, or the use according to embodiment 1-141 or 1-142, wherein the anti-THSDA antibodies are reduced by at least 50%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% compared to before treatment.

[0321] Embodiment 1-175. The method, the TACI-Ig fusion molecule or atacicept, or the use according to embodiment 1-174, wherein the anti-THSDA antibodies are not detectable after the treatment.

[0322] Embodiment 1-176. The method of embodiment 1-47 or 1-48, the TACI-Ig fusion molecule or atacicept according to embodiment 1-95 or 1-96, or the use according to embodiment 1-143 or 1-144, wherein the anti-nephrin antibodies are reduced by at least 50%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% compared to before treatment.

[0323] Embodiment 1-177. The method, the TACI-Ig fusion molecule or atacicept, or the use according to embodiment 1-176, wherein the anti-nephrin antibodies are not detectable after the treatment.

[0324] Embodiment 1-178. The method, the TACI-Ig fusion molecule or atacicept, or the use according to any one of the preceding embodiments, wherein the TACI-Ig fusion molecule or atacicept is administered weekly.

[0325] Embodiment 1-179. The method, the TACI-Ig fusion molecule or atacicept, or the use according to embodiment 1-178, wherein the TACI-Ig fusion molecule or atacicept is administered at a dose of about 150 mg / week.

[0326] Embodiment 1-180. The method, the TACI-Ig fusion molecule or atacicept, or the use according to of any one of embodiments 1-1 to 1-177, wherein the TACI-Ig fusion molecule or atacicept is administered monthly.85324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0327] Embodiment 1-181. The method, the TACI-Ig fusion molecule or atacicept, or the use according to embodiment 1-180, wherein the TACI-Ig fusion molecule or atacicept is administered at a dose of an equivalent of about 150 mg / week.

[0328] Embodiment 1-182. The method, the TACI-Ig fusion molecule or atacicept, or the use according to any one of embodiments 1-178 to 1-181, wherein the TACI-Ig or atacicept is administered for at least 6 weeks, at least 12 weeks, at least 24 weeks, at least 36 weeks, at least 48 weeks, at least 52 weeks, at least 72 weeks, at least 96 weeks, at least 108 weeks, at least 3 years, at least 5 years, at least 10 years, or more than 10 years.

[0329] Embodiment 1-183. The method, the TACI-Ig fusion molecule or atacicept, or the use according to any one of embodiments 1-178 to 1-182, wherein the TACI-Ig or atacicept is administered chronically.

[0330] Embodiment 1-184. The method of any one of embodiments 1-1, 1-3, 1-6, 1-8, 1- 10, 1-13, 1-16, 1-18, 1-21, 1-23, 1-26, 1-28, 1-31, 1-33, 1-36, 1-38, 1-42, 1-45, and 1-47, the TACI-Ig fusion molecule or atacicept according to any one of embodiments 1-49, 1-51, 1-54, 1-56, 1-58, 1-61, 1-64, 1-66, 1-69, 1-71, 1-74, 1-76, 1-79, 1-81, 1-84, 1-86, 1-90, 1-93, and 1-95, or the use according to any one of embodiments 1-97, 1-99, 1-102, 1-104, 1-106, 1-109, 1- 112, 1- 114, 1- 117, 1- 119, 1-122, 1-124, 1-127, 1-129, 1-132, 1-134, 1-138, 1-141, and 1-143, wherein the TACI extracellular domain or fragment thereof binds BAFF and APRIL.

[0331] Embodiment 1-185. The method of any one of embodiment 1-1, 1-3, 1-6, 1-8, 1- 10, 1-13, 1-16, 1-18, 1-21, 1-23, 1-26, 1-28, 1-31, 1-33, 1-36, 1-38 and 1-42, 1-45, and 1-47, the TACI-Ig fusion molecule or atacicept according to any one of embodiments 1-49, 1-51, 1-54, 1-56, 1-58, 1-61, 1-64, 1-66, 1-69, 1-71, 1-74, 1-76, 1-79, 1-81, 1-84, 1-86, 1-90, 1-93, and 1-95, or the use according to any one of embodiments 1-97, 1-99, 1-102, 1-104, 1-106, 1-109, 1- 112, 1- 114, 1- 117, 1- 119, 1-122, 1-124, 1-127, 1-129, 1-132, 1-134, 1-138, 1-141, and 1-143, wherein said TACI-Ig fusion molecule has an amino acid sequence set forth in SEQ ID NOS: 3-9 and 12., or an amino acid sequence that is at least 80% identical thereto.

[0332] Embodiment 1-186. The method according to any one of embodiments 1-1, 1-3, 1-6, 1-8, 1-10, 1-13, 1-16, 1-18, 1-21, 1-23, 1-26, 1-28, 1-31, 1-33, 1-36, 1-38 and 1-42, 1-45, and 1-47, the TACI-Ig fusion molecule or atacicept according to any one of embodiments 1-49, 1-51, 1-54, 1-56,86324900938Attorney Docket No.: VETH-016 / 01WO 327083-24311-58, 1-61, 1-64, 1-66, 1-69, 1-71, 1-74, 1-76, 1-79, 1-81, 1-84, 1-86, 1-90, 1-93, and 1-95, or the use according to any one of embodiments 1-97, 1-99, 1-102, 1-104, 1-106, 1-109, 1-112, 1-114, 1-117, 1- 119, 1-122, 1-124, 1-127, 1-129, 1-132, 1-134, 1-138, 1-141, and 1-143, wherein said TACI-Ig fusion molecule is atacicept.

[0333] Embodiment 1-187. A method of characterizing a B-cell responsive autoimmune glomerulopathy from a plurality of patients, the method comprising: a. administering to the plurality of patients having a kidney disease suspected of being a B-cell responsive autoimmune glomerulopathy, a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain; b. assessing kidney function of the patient after a round of treatment; c. selecting from the plurality of patients a patient that demonstrates improved kidney function after the round of treatment; d. collecting a serum sample from the selected patient.

[0334] Embodiment 1-188. The method of embodiment 1-187, wherein the method further comprises: e. assaying the serum sample for detection of an autoantibody against a protein that is expressed by a kidney cell; and f. characterizing the B-cell responsive autoimmune glomerulopathy of the selected patient based on the detected autoantibody.

[0335] Embodiment 1-189. The method of embodiment 1-188, wherein the kidney cell is a podocyte, glomerular epithelial cell, or a glomerular mesangial cell.87324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0336] Embodiment 1-190. A method of determining a course of treatment for a kidney disease, the method comprising: a. administering to a plurality of patients having a kidney disease suspected of being a B-cell responsive autoimmune glomerulopathy, a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain; b. assessing kidney function of the patient after a round of treatment; c. selecting from the plurality of patients a patient that demonstrates improved kidney function after the round of treatment; d. continuing the administration of the TACI-Ig fusion molecule to the patient.

[0337] Embodiment 1-191. A method of identifying a clinical trial candidate for a B-cell responsive autoimmune glomerulopathy, the method comprising: a. administering to a plurality of patients having a glomerulopathy suspected of being a B-cell responsive autoimmune glomerulopathy a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain; b. assessing kidney function of the plurality of patients after a round of treatment; c. selecting from the plurality of patients a patient that demonstrates improved kidney function after the round of treatment; and88324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 d. designating the patient as a clinical trial candidate.

[0338] Embodiment 1-192. The method of embodiment 1-191, wherein the method further comprises: e. collecting a serum sample from the clinical trial candidate.

[0339] Embodiment 1-193. The method of embodiment 1-192, wherein the method further comprises: f. assaying the serum sample for detection of an autoantibody against a protein that is expressed by a kidney cell; g. selecting a clinical trial for a B-cell responsive autoimmune glomerulopathy patient based on the detected autoantibody; h. designating the clinical trial candidate as a clinical trial participant for the selected clinical trial.

[0340] Embodiment 1-194. The method of embodiment 1-193, wherein the method further comprising having the clinical trial candidate participate in a clinical trial for the B-cell responsive autoimmune glomerulopathy.

[0341] Embodiment 1-195. The method of any one of embodiments 1-187 to 1-194, wherein the TACI-Ig fusion molecule is administered weekly.

[0342] Embodiment 1-196. The method of embodiment 1-178, wherein the TACI-Ig fusion molecule is administered at a dose of about 150 mg / week.

[0343] Embodiment 1-197. The method of any one of embodiments 1-187 to 1-194, wherein the TACI-Ig fusion molecule is administered monthly.

[0344] Embodiment 1-198. The method of embodiment 1-197, wherein the TACI-Ig fusion molecule or atacicept is administered at a dose of an equivalent of about 150 mg / week.89324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0345] Embodiment 1-199. The method of any one of embodiments 1-187 to 1-198, wherein the round of treatment is about 2 weeks, about 3 weeks, about 4 weeks, about 5 weeks, about 6 weeks, about 8 weeks, or about 10 weeks.

[0346] Embodiment 1-200. The method of any one of embodiments 1-188, 1-189, 1-193, and I- 194, wherein the detected autoantibody is an anti-PLA2R antibody or an anti- THSD7A antibody.

[0347] Embodiment 1-201. The method of embodiment 1-200, wherein the B-cell responsive autoimmune glomerulopathy is primary membranous nephropathy (pMN).

[0348] Embodiment 1-202. The method of any one of embodiments 1-188, 1-189, 1-193, and I- 194, wherein the autoantibody is an anti-nephrin antibody.

[0349] Embodiment 1-203. The method of embodiment 1-202, wherein the B-cell responsive autoimmune glomerulopathy is primary minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS).

[0350] Embodiment 1-204. The method of any one of embodiments 1-187 to 1-203, wherein the kidney function is assessed by obtaining a measure of: proteinuria, hematuria, EGFR, or a combination thereof.

[0351] Embodiment 1-205. The method of any one of embodiment 1-187 to 1-204, wherein the TACI extracellular domain or fragment thereof binds BAFF and APRIL.

[0352] Embodiment 1-206. The method of any one of embodiment 1-187 to 1-204, wherein said TACI-Ig fusion molecule has an amino acid sequence set forth in any one of SEQ ID NOS: 3-9 and 12, or an amino acid sequence that is at least 80% identical thereto.

[0353] Embodiment 1-207. The method according to any one of embodiments 1-187 to 1-205, wherein said TACI-Ig fusion molecule is atacicept.Set II

[0354] Embodiment II- 1. A method of treating a human patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof90324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand- interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein the TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein the patient has a detectable presence of autoantibodies to nephrin as measured in an immunological assay.

[0355] Embodiment II-2. The method of embodiment 11-1, wherein the detectable presence of the autoantibodies is a detectable presence in a serum sample or a kidney biopsy sample of the patient.

[0356] Embodiment II-3. The method of embodiment 11-1 or 11-2, wherein the patient is > 18 years of age.

[0357] Embodiment II-4. The method of embodiment 11-3, wherein the B-cell responsive autoimmune glomerulopathy is minimal change disease (MCD).

[0358] Embodiment II-5. The method of embodiment 11-3, wherein the the B-cell responsive autoimmune glomerulopathy is focal segmental glomerulosclerosis (FSGS).

[0359] Embodiment II-6. The method of embodiment 11-1 or 11-2, wherein the patient is < 18 years of age.

[0360] Embodiment II-7. The method of embodiment 11-6, wherein the B-cell responsive autoimmune glomerulopathy is Relapsing Frequently Nephrotic Syndrome (FRNS), Steroid- Dependent Nephrotic Syndrome (SDNS), or Steroid Resistant Nephrotic Syndrome (SRNS).

[0361] Embodiment II-8. The method of any one of embodiments 11-1 to 11-7, wherein the patient has been on a regimen of another therapeutic agent, prior to treatment with the TACI-Ig fusion molecule.91324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0362] Embodiment II-9. The method of embodiment II-8, wherein the patient remains on the regimen of the another therapeutic agent during treatment with the TACI-Ig fusion molecule.

[0363] Embodiment II- 10. The method of any one of embodiments II- 1 to II-7, wherein the patient is placed on a regimen of another therapeutic agent concomitantly with treatment with the TACI-Ig fusion molecule.

[0364] Embodiment II- 11. The method of any one of embodiments II-8 to II- 10, wherein the another therapeutic agent is a renin-angiotensin-aldosterone system inhibitor (RAASi).

[0365] Embodiment 11-12. The method of embodiment II- 11, wherein the RAASi is an angiotensin converting enzyme inhibitor (ACEi) and / or angiotensin II receptor blocker (ARB).

[0366] Embodiment 11-13. The method of any one of embodiments II-8 to II- 10, wherein the another therapeutic agent is a sodium-glucose cotransporter-2 inhibitors (SGLT2i), a mineralocorticoid receptor antagonist (MRA), an endothelin receptor antagonists (ERA) or a glucagon-like peptide- 1 receptor agonist (GLP-1RA).

[0367] Embodiment 11-14. The method of any one of embodiments II- 1 to 11-13, wherein the patient prior to treatment has proteinuria with a urine protein : creatinine ratio (UPCR) of greater than 1 mg / mg.

[0368] Embodiment 11-15. The method of any one of embodiments II- 1 to 11-14, wherein the patient prior to treatment has reduced kidney function compared to a healthy subject, as determined by estimated glomerular flow rate (eGFR).

[0369] Embodiment 11-16. The method of embodiment 11-15, wherein the patient prior to treatment has an eGFR of about 30 ml / min / 1.73m2or higher.

[0370] Embodiment 11-17. The method of any one of embodiments II- 1 to 11-16, wherein the administration reduces the amount of proteinuria compared to baseline before the start of treatment.

[0371] Embodiment 11-18. The method of embodiment 11-17, wherein the proteinuria is reduced by at least 10%, at least 20%, at least 25%, at least 30%, at least 35%, or at least 40% compared to the baseline.92324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0372] Embodiment 11-19. The method of embodiment 11-17 or 11-18, wherein the proteinuria is determined based on a measure of mg protein / L urine.

[0373] Embodiment 11-20. The method of embodiment 11-17 or 11-18, wherein the proteinuria is determined based on a urine protein : creatinine ratio (UPCR).

[0374] Embodiment 11-21. The method of embodiment 11-17 or 11-18, wherein the proteinuria is determined based on a urine albumin : creatinine ratio (UACR).

[0375] Embodiment 11-22. The method of any one of embodiments II- 1 to 11-20, wherein the eGFR increases, or is decreased by not more than 10% compared to baseline before the start of treatment.

[0376] Embodiment 11-23. The method of any one of embodiments II- 1 to 11-22, wherein the administration reduces the amount of the autoantibodies to nephrin in the patient compared to baseline before the start of treatment.

[0377] Embodiment 11-24. The method of embodiment 11-23, wherein the one or more autoantibodies are reduced by at least 50%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% compared to before the start of treatment.

[0378] Embodiment 11-25. The method of embodiment 11-23, wherein the one or more autoantibodies becomes undetectable to the immunological assay in the patient after the administration.

[0379] Embodiment 11-26. The method of any one embodiments II- 1 to 11-25, wherein the TACI-Ig fusion molecule is administered weekly.

[0380] Embodiment 11-27. The method of to embodiment 11-26, wherein the TACI-Ig fusion molecule is administered at a dose of between about 75 mg / week and about 150 mg / week.

[0381] Embodiment 11-28. The method of to embodiment 11-26, wherein the TACI-Ig fusion molecule is administered at a dose of about 75 mg / week or about 150 mg / week.

[0382] Embodiment 11-29. The method of any one of embodiments II- 1 to 11-25, wherein the TACI-Ig fusion molecule is administered monthly.93324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0383] Embodiment 11-30. The method of embodiment 11-29, wherein the TACI-Ig fusion molecule is administered at a dose of between about 300 mg / month and about 600 mg / month.

[0384] Embodiment II- 31. The method of embodiment 11-30, wherein the TACI-Ig fusion molecule is administered at a dose of about 300 mg / month, about 450 mg / month, or about 600 mg / month.

[0385] Embodiment 11-32. The method of any one of embodiments II- 1 to II-31, wherein the TACI-Ig fusion molecule is administered for at least 6 weeks, at least 12 weeks, at least 24 weeks, at least 36 weeks, at least 48 weeks, at least 52 weeks, at least 72 weeks, at least 96 weeks, at least 108 weeks, at least 3 years, at least 5 years, or at least 10 years.

[0386] Embodiment 11-33. The method of any one of embodiments II- 1 to 11-32, wherein the TACI-Ig fusion molecule is administered chronically.

[0387] Embodiment 11-34. The method of any one of embodiments II- 1 to 11-33, wherein the TACI-Ig fusion molecule is administered subcutaneously.

[0388] Embodiment 11-35. The method of any one embodiments II-l to 11-34, wherein the TACI extracellular domain has an amino acid sequence set forth in SEQ ID NO: 1, or an amino acid sequence that is at least 80% identical thereto.

[0389] Embodiment 11-36. The method of embodiment 11-35, wherein the human immunoglobulin-constant domain has an amino acid sequence set forth in SEQ ID NO: 2, or an amino acid sequence that is at least 80% identical thereto.

[0390] Embodiment 11-37. The method of any one embodiments II- 1 to 11-34, wherein the TACI-Ig fusion molecule has an amino acid sequence set forth in SEQ ID NO: 3, or an amino acid sequence that is at least 80% identical thereto.

[0391] Embodiment 11-38. The method of any one embodiments II-l to 11-34, wherein the TACI-Ig fusion molecule, wherein the TACI-Ig fusion molecule is atacicept.

[0392] Embodiment 11-39. The method of any one embodiments II-l to 11-34, wherein the TACI-Ig fusion molecule has an amino acid sequence set forth in any one of SEQ ID NOS: 4-9 and 12, an amino acid sequence that is at least 80% identical thereto.94324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0393] Embodiment 11-40. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein the TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the patient has a detectable presence of autoantibodies to nephrin as measured in an immunological assay.

[0394] Embodiment 11-41. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein the TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence of autoantibodies to nephrin as measured in an immunological assay.

[0395] Embodiment 11-42. A method of treating a human patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand- interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein the TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and95324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431(ii) a human immunoglobulin-constant domain, wherein the patient has a detectable presence of autoantibodies to PLA2R or autoantibodies to THSD7A as measured in an immunological assay.

[0396] Embodiment 11-43. The method of embodiment 11-42, wherein the detectable presence of the autoantibodies is a detectable presence in a serum sample or a kidney biopsy sample of the patient.

[0397] Embodiment 11-44. The method of embodiment 11-42 or 11-43, wherein the B-cell responsive autoimmune glomerulopathy is primary membranous nephropathy (pMN).

[0398] Embodiment 11-45. The method of any one of embodiments 11-42 to 11-44, wherein the patient is > 18 years of age.

[0399] Embodiment 11-46. The method of any one of embodiments 11-42 to 11-45, wherein the patient has been on a regimen of another therapeutic agent, prior to treatment with the TACI-Ig fusion molecule.

[0400] Embodiment 11-47. The method of embodiment 11-46, wherein the patient remains on the regimen of the another therapeutic agent during treatment with the TACI-Ig fusion molecule.

[0401] Embodiment 11-48. The method of any one of embodiments 11-42 to 11-47, wherein the patient is placed on a regimen of another therapeutic agent concomitantly with treatment with the TACI-Ig fusion molecule.

[0402] Embodiment 11-49. The method of any one of embodiments 11-46 to 11-48, wherein the another therapeutic agent is a renin-angiotensin-aldosterone system inhibitor (RAASi).

[0403] Embodiment 11-50. The method of embodiment 11-49, wherein the RAASi is an angiotensin converting enzyme inhibitor (ACEi) and / or angiotensin II receptor blocker (ARB).

[0404] Embodiment II- 51. The method of any one of embodiments 11-46 to 11-48, wherein the another therapeutic agent is a sodium-glucose cotransporter-2 inhibitors (SGLT2i), a mineralocorticoid receptor antagonist (MRA), an endothelin receptor antagonists (ERA) or a glucagon-like peptide- 1 receptor agonist (GLP-1RA).96324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0405] Embodiment 11-52. The method of any one of embodiments 11-42 to 11-51, wherein the patient prior to treatment has proteinuria with a urine protein : creatinine ratio (UPCR) of greater than 1 mg / mg, assessed by urine specimens from 24-hour urine collection.

[0406] Embodiment 11-53. The method of any one of embodiments 11-42 to 11-52, wherein the patient prior to treatment has reduced kidney function compared to a healthy subject, as determined by estimated glomerular flow rate (eGFR).

[0407] Embodiment 11-54. The method of embodiment 11-53, wherein the patient prior to treatment has an eGFR of about 30 ml / min / 1.73m2or higher.

[0408] Embodiment 11-55. The method of any one of embodiments 11-42 to 11-54, wherein the administration reduces the amount of proteinuria compared to baseline before the start of treatment.

[0409] Embodiment 11-56. The method of embodiment 11-55, wherein the proteinuria is reduced by at least 10%, at least 20%, at least 25%, at least 30%, at least 35%, or at least 40% compared to the baseline.

[0410] Embodiment 11-57. The method of embodiment 11-55 or 11-56, wherein the proteinuria is determined based on a measure of mg protein / L urine.

[0411] Embodiment 11-58. The method of embodiment 11-55 or 11-56, wherein the proteinuria is determined based on a urine protein : creatinine ratio (UPCR).

[0412] Embodiment 11-59. The method of embodiment 11-55 or 11-56, wherein the proteinuria is determined based on a urine albumin : creatinine ratio (UACR).

[0413] Embodiment 11-60. The method of any one of embodiments 11-42 to 11-58, wherein the eGFR increases, or is decreased by not more than 10% compared to baseline before the start of treatment.

[0414] Embodiment 11-61. The method of any one of embodiments 11-42 to 11-60, wherein the administration reduces the amount of the autoantibodies to nephrin in the patient compared to baseline before the start of treatment.97324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0415] Embodiment 11-62. The method of embodiment 11-61, wherein the one or more autoantibodies are reduced by at least 50%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% compared to before the start of treatment.

[0416] Embodiment 11-63. The method of embodiment 11-61, wherein the one or more autoantibodies becomes undetectable to the immunological assay in the patient after the administration.

[0417] Embodiment 11-64. The method of any one embodiments 11-42 to 11-63, wherein the TACI-Ig fusion molecule is administered weekly.

[0418] Embodiment 11-65. The method of to embodiment 11-64, wherein the TACI-Ig fusion molecule is administered at a dose of between about 75 mg / week and about 150 mg / week.

[0419] Embodiment 11-66. The method of to embodiment 11-65, wherein the TACI-Ig fusion molecule is administered at a dose of about 75 mg / week or about 150 mg / week.

[0420] Embodiment 11-67. The method of any one of embodiments 11-42 to 11-63, wherein the TACI-Ig fusion molecule is administered monthly.

[0421] Embodiment 11-68. The method of embodiment 11-67, wherein the TACI-Ig fusion molecule is administered at a dose of between about 300 mg / month and about 600 mg / month.

[0422] Embodiment 11-69. The method of embodiment 11-68, wherein the TACI-Ig fusion molecule is administered at a dose of about 300 mg / month, about 450 mg / month, or about 600 mg / month.

[0423] Embodiment 11-70. The method of any one of embodiments 11-64- to 11-69, wherein the TACI-Ig fusion molecule is administered for at least 6 weeks, at least 12 weeks, at least 24 weeks, at least 36 weeks, at least 48 weeks, at least 52 weeks, at least 72 weeks, at least 96 weeks, at least 108 weeks, at least 3 years, at least 5 years, or at least 10 years.

[0424] Embodiment 11-71. The method of any one of embodiments 11-42 to 11-70, wherein the TACI-Ig fusion molecule is administered chronically.98324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0425] Embodiment 11-72. The method of any one of embodiments 11-42 to 11-71, wherein the TACI-Ig fusion molecule is administered subcutaneously.

[0426] Embodiment 11-73. The method of any one embodiments 11-42 to 11-72, wherein the TACI extracellular domain has an amino acid sequence set forth in SEQ ID NO: 1, or an amino acid sequence that is at least 80% identical thereto.

[0427] Embodiment 11-74. The method of embodiment 11-73, wherein the human immunoglobulin-constant domain has an amino acid sequence set forth in SEQ ID NO: 2, or an amino acid sequence that is at least 80% identical thereto.

[0428] Embodiment 11-75. The method of any one embodiments 11-42 to 11-72, wherein the TACI-Ig fusion molecule has an amino acid sequence set forth in SEQ ID NO: 3, or an amino acid sequence that is at least 80% identical thereto.

[0429] Embodiment 11-76. The method of any one embodiments 11-42 to 11-72, wherein the TACI-Ig fusion molecule, wherein the TACI-Ig fusion molecule is atacicept.

[0430] Embodiment 11-77. The method of any one embodiments 11-42 to 11-72, wherein the TACI-Ig fusion molecule has an amino acid sequence set forth in any one of SEQ ID NOS: 4-9 and 12, an amino acid sequence that is at least 80% identical thereto.

[0431] Embodiment 11-78. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein the TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the patient has a detectable presence of autoantibodies to PLA2R or autoantibodies to THSD7A as measured in an immunological assay.99324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0432] Embodiment 11-79. Use of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein the TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the patient has a detectable presence of autoantibodies to PLA2R or autoantibodies to THSD7A as measured in an immunological assay.

[0433] Embodiment 11-80. A method of characterizing a B-cell responsive autoimmune glomerulopathy from a plurality of human patients, the method comprising: a. administering, to the plurality of patients having a kidney disease suspected of being a B-cell responsive autoimmune glomerulopathy, a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain; b. assessing kidney function of the patient after a round of treatment; c. selecting from the plurality of patients a patient that demonstrates improved kidney function after the round of treatment; and d. collecting a serum sample from the selected patient.

[0434] Embodiment II-81. The method of embodiment 11-80, wherein the method further comprises:100324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 e. assaying the serum sample for detection of an autoantibody against a protein that is expressed by a kidney cell; and f. characterizing the B-cell responsive autoimmune glomerulopathy of the selected patient based on the detected auto-antibody.

[0435] Embodiment 11-82. The method of embodiment 11-81, wherein the kidney cell is a podocyte, glomerular epithelial cell, or a glomerular mesangial cell.

[0436] Embodiment 11-83. A method of determining a course of treatment for a kidney disease, the method comprising: a. administering to a plurality of human patients having a kidney disease suspected of being a B-cell responsive autoimmune glomerulopathy, a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain; b. assessing kidney function of the patient after a round of treatment; c. selecting from the plurality of patients a patient that demonstrates improved kidney function after the round of treatment; and d. continuing the administration of the TACI-Ig fusion molecule to the patient.

[0437] Embodiment 11-84. A method of identifying a clinical trial candidate for a B-cell responsive autoimmune glomerulopathy, the method comprising: a. administering to a plurality of patients having a glomerulopathy suspected of being a B-cell responsive autoimmune glomerulopathy a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:101324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain; b. assessing kidney function of the plurality of patients after a round of treatment; c. selecting from the plurality of patients a patient that demonstrates improved kidney function after the round of treatment; and d. designating the patient as a clinical trial candidate.

[0438] Embodiment 11-85. The method of embodiment 11-84, wherein the method further comprises: e. collecting a serum sample from the clinical trial candidate.

[0439] Embodiment 11-86. The method of embodiment 11-85, wherein the method further comprises: f. assaying the serum sample for detection of an autoantibody against a protein that is expressed by a kidney cell; g. selecting a clinical trial for a B-cell responsive autoimmune glomerulopathy patient based on the detected autoantibody; and h. designating the clinical trial candidate as a clinical trial participant for the selected clinical trial.

[0440] Embodiment 11-87. The method of embodiment 11-86, wherein the method further comprising having the clinical trial candidate participate in a clinical trial for the B-cell responsive autoimmune glomerulopathy.

[0441] Embodiment 11-88. The method of any one of embodiments 11-80 to 11-87, wherein the TACI-Ig fusion molecule is administered weekly.

[0442] Embodiment 11-89. The method of embodiment 11-88, wherein the TACI-Ig fusion molecule is administered at a dose of between about 75 mg / week and about 150 mg / week.102324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0443] Embodiment 11-90. The method of any one of embodiments 11-80 to 11-87, wherein the TACI-Ig fusion molecule is administered monthly.

[0444] Embodiment 11-91. The method of embodiment 11-90, wherein the TACI-Ig fusion molecule or atacicept is administered at a dose of between about 300 mg / month and about 600 mg / month.

[0445] Embodiment 11-92. The method of any one of embodiments 11-80 to 11-91, wherein the round of treatment is about 2 weeks, about 3 weeks, about 4 weeks, about 5 weeks, about 6 weeks, about 8 weeks, or about 10 weeks.

[0446] Embodiment 11-93. The method of any one of embodiments 11-86 and 11-87, wherein the detected autoantibody is an anti-PLA2R antibody or an anti- THSD7A antibody.

[0447] Embodiment 11-94. The method of embodiment 11-93, wherein the B-cell responsive autoimmune glomerulopathy is primary membranous nephropathy (pMN).

[0448] Embodiment 11-95. The method of any one of embodiments 11-86 and 11-87, wherein the auto-antibody is an anti-nephrin antibody.

[0449] Embodiment 11-96. The method of embodiment 11-95, wherein the B-cell responsive autoimmune glomerulopathy is primary minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS).

[0450] Embodiment 11-97. The method of any one of embodiments 11-80 to 11-96, wherein the kidney function is assessed by obtaining a measure of: proteinuria, hematuria, eGFR, or a combination thereof.

[0451] Embodiment 11-98. The method of any one of embodiment 11-80 to 11-97, wherein the TACI extracellular domain or fragment thereof binds BAFF and APRIL.

[0452] Embodiment 11-99. The method of any one of embodiment 11-80 to 11-98, wherein said TACI-Ig fusion molecule has an amino acid sequence set forth in any one of SEQ ID NOS: 3-9 and 12, or an amino acid sequence that is at least 80% identical thereto.103324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0453] Embodiment II- 100. The method according to any one of embodiments 11-80 to 11-99, wherein said TACI-Ig fusion molecule is atacicept.EXAMPLESExample 1 - Basket StudyGoal (for all indications)

[0454] A clinical study for multiple indications (a “basket study”) is carried out evaluate the effect of atacicept on the proportion of participants achieving complete remission (CR), or partial remission (PR) of proteinuria, in participants with various glomerulopathies that are, or suspected to be based on autoimmune cases (e.g. autoantibodies).Study design (for all indications)

[0455] The study is composed of a (up to) 4-week Screening Period, 52-week Open-label Treatment Period, and 26-week Safety Follow-up Period, evaluating the safety, tolerability, efficacy and pharmacokinetics (PK) of atacicept over 52 weeks of once weekly 150 mg subcutaneous (SC) injections (see FIG. 5). Periodic safety, efficacy, and PK assessments is performed including attendance at Weeks 36 and 52 for key study assessments.

[0456] The primary efficacy endpoint of urine protein-to-creatinine ratio (UPCR) is assessed by specimens from 24-hour urine collection. Adverse events (AE) and concomitant medications / therapies is monitored and recorded from the time of informed consent / assent through study completion.

[0457] Participants are required to be on a stable maximum tolerated or labelled dose of a renin- angiotensin-aldosterone system inhibitor (RAASi), e.g., an angiotensin converting enzyme inhibitor (ACEi) and / or an angiotensin II receptor blocker (ARB), or a sodium-glucose cotransporter-2 inhibitors (SGLT2i), a mineralocorticoid receptor antagonist (MRA), an endothelin receptor antagonists (ERA) and / or a glucagon-like peptide- 1 receptor agonist (GLP- 1RA), for at least 12 weeks prior to screening and should remain stable for the duration of the study.104324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0458] Blood and urine biorepository samples is collected at all study visits and stored for future exploratory biomarker analysis to better understand disease and drug effects.Overall patient selection

[0459] During screening of patients, key inclusion criteria were:• Male or female consenting participant, or parent / legal guardian (as appropriate) who has the ability to understand a written informed consent / assent form and is willing and able to provide written informed consent / assent.• On a stable prescribed regimen of RAASi (e.g. ACEi or ARB) for at least 12 weeks that is at the maximum labelled or tolerated dose at screening, or an alternative regiment w / o RAASi provided their treatment management, e.g., with SGLT2i’s, MRAs, ERAs, and / or GLP-lRas, is standard of care (SoC) according to local guidelines.

[0460] Key exclusion criteria are:• Evidence of rapidly progressive glomerulonephritis (loss of > 50% of eGFR within 3 months prior to and at Screening)• Acute kidney injury with failure of kidney function to return within 10% of baseline in the 3 months prior screening to and through Day 1• Severe kidney impairment (eGFR <15 ml / min / 1.73m2) including the need for dialysis or kidney replacement therapy.• Kidney transplantation or other organ transplantation prior to, or expected during the study, with the exception of corneal transplants.• Uncontrolled diabetes.• History of tuberculosis (TB), untreated latent TB infection (LTBI), or evidence of LTBI.• Clinically significant or predefined blood abnormalities, e.g., serum IgG, aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase, bilirubin, hemoglobin, platelets, neutrophil count, etc. being beyond threshold.• Any prior or current history of severe IgA-related disease, including severe IgA Vasculitis Nephritis (IgAVN) requiring corticosteroids and IgA vasculitis with, e.g., intussusception, gastrointestinal haemorrhage requiring transfusion, intestinal ischemia,105324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 perforation, or abdominal pain persisting more than one day and unresponsive to standard analgesics (acetaminophen and / or NSAIDs).• Active, clinically significant viral, bacterial, or fungal infection, chronic infections, or cancer.Assays

[0461] Samples are taken longitudinally at prescheduled timepoints. All safety evaluations are conducted based on the Safety Population and the safety data of each enrollment population and cohort are summarized by descriptive statistics. Safety is assessed by physical examinations, vital signs, electrocardiograms (ECG), clinical laboratory tests, and evaluation of AE / SAEs, with attention given to infections, local tolerability / injection site reaction (ISRs), and hypersensitivity reactions.

[0462] The assessments of immunoglobulins (e.g., IgG) are performed by an immunoturbidometric method as part of a standard central lab panel.

[0463] The primary analysis of proteinuria assesses UPCR data determined from a urine specimen, e.g., 24-hour urine specimens. UPCR analyses are performed on natural log- transformed data. The relative change from baseline in UPCR are analyzed using mixed-effects model for repeated measures (MMRM), where the response variable is natural log-transformed UPCR, and with fixed effects time (nominal visits in weeks) and baseline UPCR. The geometric mean of percentage change derived from least-square means estimate and corresponding 95% confidence interval (CI) for each visit are reported. A similar analysis is performed, as appropriate, anti-PLA2R antibody, and anti-nephrin antibodies.

[0464] The eGFR for each visit is determined using the CKD-EPI equation for adults >18 years of age and CKiD U25 for adolescents >15 to <18 years of age, at Screening, and for the duration of the study.

[0465] Anti-nephrin, anti-THSD7A, and anti-PLA2R antibodies from participant samples may be detected by any autoantibody assay known in the art, for example an immunological assay. The immunological assay may be, e.g., indirect immunofluorescence assay (IEF), enzyme-linked immunosorbent assay (ELISA), nephelometry or immunoblotting (Aggarwal, “Role of106324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 autoantibody testing”, Best Practice & Research Clinical Rheumatology, Volume 28, Issue 6, 2014).

[0466] The survival curve of time to >50% reduction in autoantibodies is estimated using Kaplan-Meier method.

[0467] Atacicept concentration in serum is summarized at nominal timepoints using descriptive statistics by enrollment population and cohort assignment. Descriptive statistics is used to summarize PK parameters by enrollment population and cohort as well as overall.Example 2 - pMNGoal

[0468] A clinical study is carried out, as part of the basket study, to evaluate the effect of atacicept on the proportion of participants with pMN associated with anti-PLA2R antibodies (n <40) achieving complete remission (CR), or partial remission (PR) of proteinuria. A summary of this study is shown in FIG. 5. pMN patient selection

[0469] During screening of patients, key inclusion criteria, for two pMN cohorts, are (in addition to the overall inclusion criteria in Example 1) as provided in Table 2:Table 2: Inclusion Criteria for pMN Cohorts107324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0470] The intent for cohort pMN-1 (incident disease), is to evaluate atacicept as first-line immunosuppressive therapy, and therefore no prior immunosuppressive therapy is allowed.

[0471] For cohort pMN-2 with relapsed or resistant disease, prior history of immunosuppressive therapy is allowed, provided the medications are discontinued at least 1 month prior to enrollment. Prior treatment with anti-CD20 antibody therapy (e.g. rituximab) is allowed provided the last dose administered was at least 5 months prior to Screening and reconstitution of B cell counts (above lower limit of normal for age) have been confirmed using local labs prior to enrollment. Alkylating agents such as cyclophosphamide or chlorambucil are prohibited prior to and during the study.

[0472] Key exclusion criteria were (in addition to the overall exclusion criteria in Example 1):• Acute Reduction in Anti-PLA2R antibodies, i.e., >50% in the 6 months prior to Screening• Diagnosis of IgANTreatment108324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0473] In the study atacicept 150 mg in an aqueous formulation is self-administered SC QW (weekly subcutaneous injections) via pre-filled syringe (PFS) and provided to all participants. The atacicept formulation contains the following excipients: trehalose as a stabilizing agent and sodium acetate buffer (pH 5.0). Unit dosage strength for atacicept (per 1.0 ml) is 150 mg. The injections are performed SC into the abdomen (anterior abdominal wall) or thighs, using the PFS and standard SC injection technique. Injection sites were rotated for all doses and were per instruction at least 5 centimeters away (approximately 2 inches) from the previous injection in areas without any existing skin pathology. The injections are to be administered at approximately the same time and day of each week.

[0474] Additional administration dosages are also tested in the study, including monthly injections of 300 mg per month, 450 mg per month, and 600 mg per month.

[0475] Participants are required to be on a stable prescribed regimen of RAASi that is at the maximum labeled or tolerated dose (or alternative SOC as noted above) for at least 12 weeks prior to the study, and for the duration of the study (if clinically appropriate).

[0476] Atacicept administration is initiated in addition to stable supportive SOC therapy that may include stable low dose glucocorticoid (CGS; <10 mg / day prednisolone or equivalent) therapy and / or Calcineurin inhibitors (CNIs). In cases of inadequate control of disease (in the opinion of the investigator (including review of anti-PLA2R antibody titer), the GCS / CNI treatment regimen may be modified. B -cell-directed biologic therapies including but not limited to rituximab, obinutuzumab, ofatumumab and alkylating agents such as cyclophosphamide or chlorambucil are prohibited.Endpoints

[0477] The endpoints of the study are as shown in Table 3:Table 3 - Endpoints for pMN cohorts109324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431110324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431Example 3 - Nephrotic syndrome with anti-nephrin autoantibodiesGoal

[0478] A clinical study is carried out, as part of the basket study, to evaluate the effect of atacicept on the proportion of participants with an anti-nephrin glomerulopathy exhibiting nephrotic syndrome (NS) associated with anti-nephrin antibodies (n <40) achieving complete remission (CR), or partial remission (PR) of proteinuria. The anti-nephrin glomerulopathy patients include the following cohorts:• NS-1 MCD / FSGS (Adults): Adult participants (>18 to 80 years of age) diagnosed with MCD or FSGS with evidence of anti-nephrin antibodies by biopsy or serologic assay and no prior treatment for new-onset nephrotic syndrome or current relapse.• NS-2 FRNS / SDNS / SRNS (Pediatrics): Pediatric participants (>10 to 18 years of age) with nephrotic syndrome, with evidence of anti-nephrin antibodies by biopsy or serologic assay may be diagnosed as having Frequently Relapsing Nephrotic Syndrome (FRNS) or Steroid-Dependent Nephrotic Syndrome (SDNS) when relapsing or responsive to steroid treatment. Patients who are resistant to steroid treatment may be diagnosed as having Steroid Resistant Nephrotic Syndrome (SRNS) .

[0479] A summary of this study is shown in FIG. 5.Patient selection

[0480] During screening of patients, key inclusion criteria were (in addition to the overall inclusion criteria in Example 1) as provided in Table 3:Table 3: Inclusion Criteria111324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0481] Additional criteria for pediatric anti-nephrin glomerulopathy (FRNS, SDNS, or SRNS) are as follows:• FRNS: Two or more relapses within 6 months, or 3 or more relapses within 12 months• SDNS: Relapse within 14 days of discontinuing a course of glucocorticosteroids (including relapse during glucocorticoid dose tapering).• SRNS: Unable to achieve complete remission after 6 weeks of high dose glucocorticoids

[0482] Key exclusion criteria (in addition to the overall exclusion criteria in Example 1):• Secondary causes ofMCD• Prior treatment with anti-CD20 antibody within the past 5 months.Administration of alkylating agents, including but not limited to cyclophosphamide, in the 6 months prior to Screening112324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431• Genetic cause of SRNSTreatment

[0483] In the study atacicept 150 mg in an aqueous formulation is self-administered SC QW (weekly subcutaneous injections) via pre-filled syringe (PFS) and provided to all participants. The atacicept formulation contains the following excipients: trehalose as a stabilizing agent and sodium acetate buffer (pH 5.0). Unit dosage strength for atacicept (per 1.0 ml) is 150 mg. The injections are performed SC into the abdomen (anterior abdominal wall) or thighs, using the PFS and standard SC injection technique. Injection sites were rotated for all doses and were per instruction at least 5 centimeters away (approximately 2 inches) from the previous injection in areas without any existing skin pathology. The injections were intended to be administered at approximately the same time and day of each week.

[0484] Additional administration dosages are also tested in the study, including monthly injections of 300 mg per month, 450 mg per month, and 600 mg per month.

[0485] Participants are required to be on a stable prescribed regimen of RAASi that is at the maximum labeled or tolerated dose (or alternative SOC as noted above) for at least 12 weeks prior to the study, and for the duration of the study (if clinically appropriate).

[0486] Atacicept administration is initiated in addition to stable supportive SOC therapy that may include stable immunosuppression treatment (1ST), excluding other B-cell-directed biologic therapies and alkylating agents.Endpoints

[0487] The endpoints of the study are as shown in Table 4:Table 4 - Endpoints113324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431114324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431Example 4 - Evaluation of patients with glomerulopathiesGoal

[0488] A study (or treatment plan) is carried out to evaluate the effect of atacicept on participants with a glomerulopathy. A flowchart 100 schematically showing aspects of this study (or treatment plan) is shown in FIG. 6.Patient selection

[0489] During screening of patients, key inclusion criteria were (in addition to the overall inclusion criteria in Example 1):• >15 to <80 years of age at the time of signing the informed consent or assent (as appropriate)• Lack of detectable anti-nephrin and anti-PLA2R antibodies at Screening.• UPCR > 0.75 g / g (grams protein per grams creatinine) at Screening, or eGFR < 90 ml / min / 1.73m2 and >40 ml / min / 1.73m2 (CKD-EPI) at Screening.• Normal B-cell count defined as 1000 and 4800 lymphocytes per pL of blood.

[0490] Key exclusion criteria are:• Evidence of rapidly progressive glomerulonephritis (loss of > 50% of eGFR within 3 months prior to and at Screening)• Acute kidney injury with failure of kidney function to return within 10% of baseline in the 3 months prior screening to and through Day 1• Severe kidney impairment (eGFR <15 ml / min / 1.73m2) including the need for dialysis or kidney replacement therapy.115324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431• Kidney transplantation or other organ transplantation prior to, or expected during the study, with the exception of corneal transplants.• History of tuberculosis (TB), untreated latent TB infection (LTBI), or evidence of LTBI.• Clinically significant or predefined blood abnormalities, e.g., serum IgG, aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase, bilirubin, hemoglobin, platelets, neutrophil count, etc. being beyond threshold.• Any prior or current history of severe IgA-related disease, including severe IgAVN requiring corticosteroids and IgA vasculitis with, e.g., intussusception, gastrointestinal haemorrhage requiring transfusion, intestinal ischemia, perforation, or abdominal pain persisting more than one day and unresponsive to standard analgesics (acetaminophen and / or NSAIDs).• Active, clinically significant viral, bacterial or fungal infection, chronic infections, or cancer.Treatment

[0491] In the study Atacicept 150 mg is self-administered SC QW (weekly subcutaneous injections) via pre-filled syringe (PFS) and provided to all participants. The injections are performed SC into the abdomen (anterior abdominal wall) or thighs, using the PFS and standard SC injection technique. Injection sites were rotated for all doses and were per instruction at least 5 centimeters away (approximately 2 inches) from the previous injection in areas without any existing skin pathology. The injections were intended to be administered at approximately the same time and day of each week.

[0492] Participants are required to be on a stable prescribed regimen of RAASi that is at the maximum labeled or tolerated dose (or alternative SOC as noted above) for at least 12 weeks prior to the study, and for the duration of the study (if clinically appropriate).

[0493] Atacicept administration is initiated in addition to stable supportive SOC therapy that may include stable immunosuppression treatment (1ST), excluding other B-cell-directed biologic therapies and alkylating agents.Evaluation of kidney function116324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431

[0494] As schematically shown in FIG. 6 as block 103, the kidney function of the participants are evaluated as follows:• Change from baseline in UPCR at Weeks 2, 4, 6, 8, and 10. o If UPCR is reduced to at least 10% below baseline in a patient, the patient is designated as having “atacicept-sensitive glomerulopathy”. Otherwise, the patient is designated as having “atacicept-insensitive glomerulopathy”.• Changes from baseline in eGFR (CKD-EPI) at Weeks 2. 4, 6, 8, and 10. o If UPCR is at least maintained in a patient, the patient is designated as having “atacicept-sensitive glomerulopathy”. Otherwise, the patient is designated as having “atacicept-insensitive glomerulopathy”.Selection for “atacicept-sensitive glomerulopathy ”

[0495] As schematically shown in FIG. 6 as block 105, if after week 10, the patient was not designated as having “atacicept-sensitive glomerulopathy”, then the trial is over for him / her.

[0496] However, if the patient was designated as having “atacicept-sensitive glomerulopathy” at any point, then s / he proceeds with phase 2 of the study.Phase 2

[0497] Phase 2 of the study has three options.

[0498] As schematically shown in FIG. 6 as block 111, the patient is given the option of continuing treatment with a TACLIg molecule. This TACI-Ig molecule may be same or different from the TACI-Ig molecule used in phase 1.

[0499] As schematically shown in FIG. 6 as block 113, the patient may proceed with further evaluation, serum sample from the selected patient may be collected, then assayed for detection of an autoantibody and determination of an autoantigen of the autoantibody. These serum samples is collected, and assayed to detect autoantibodies and to determine the autoantigen for the autoantibodies. The assay may be an immunological assay (e.g. ELISA) with a panel of suspected auto-antigens that may, but have not been previously established to, play a role in kidney117324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 pathogenesis, with which binding of the autoantibodies detected in the serum sample is tested. The panel may include candidate autoantigen that are expressed by a kidney cell. The assay may be proteomic assay, e.g., two-dimensional gel electrophoresis (2 -DE), image analysis, or mass spectrometry (MS). Where the determined autoantigen is a protein expressed by a kidney cell, the corresponding autoantibodies may be designated as a marker for a B-cell responsive autoimmune glomerulopathy.

[0500] As schematically shown in FIG. 6 as block 115, the patient may be designated as a clinical trial candidate for treatment of a B-cell responsive autoimmune glomerulopathy. A serum sample is taken from the patient assayed to detect autoantibodies and to determine the autoantigen for the autoantibodies. The assay may be an immunological assay (e.g., ELISA) with a panel of autoantigens, optionally expressed by kidney cells, e.g., nephrin or THSD7A. The identity of the autoantigen may be used to select a clinical trial for the clinical trial candidate, then have the clinical trial candidate participate in a selected clinical trial.118324900938

Claims

Attorney Docket No.: VETH-016 / 01WO 327083-2431CLAIMS1. A method of treating a human patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein the TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein the patient has a detectable presence of autoantibodies to nephrin as measured in an immunological assay.

2. The method of claim 1, wherein the detectable presence of the autoantibodies is a detectable presence in a serum sample or a kidney biopsy sample of the patient.

3. The method of claim 1 or claim 2, wherein the patient is > 18 years of age.

4. The method of claim 3, wherein the B-cell responsive autoimmune glomerulopathy is minimal change disease (MCD).

5. The method of claim 3, wherein the the B-cell responsive autoimmune glomerulopathy is focal segmental glomerulosclerosis (FSGS).

6. The method of claim 1 or claim 2, wherein the patient is < 18 years of age.

7. The method of claim 6, wherein the B-cell responsive autoimmune glomerulopathy is Relapsing Frequently Nephrotic Syndrome (FRNS), Steroid-Dependent Nephrotic Syndrome (SDNS), or Steroid Resistant Nephrotic Syndrome (SRNS).

8. The method of any one of claims 1-7, wherein the patient has been on a regimen of another therapeutic agent, prior to treatment with the TACI-Ig fusion molecule.

9. The method of claim 8, wherein the patient remains on the regimen of the another therapeutic agent during treatment with the TACI-Ig fusion molecule.

10. The method of any one of claims 1-7, wherein the patient is placed on a regimen of another therapeutic agent concomitantly with treatment with the TACI-Ig fusion molecule.

11. The method of any one of claims 8-10, wherein the another therapeutic agent is a renin- angiotensin-aldosterone system inhibitor (RAASi).

12. The method of claim 11, wherein the RAASi is an angiotensin converting enzyme inhibitor (ACEi) and / or angiotensin II receptor blocker (ARB).119324900938Attorney Docket No.: VETH-016 / 01WO 327083-243113. The method of any one of claims 8-10, wherein the another therapeutic agent is a sodium-glucose cotransporter-2 inhibitors (SGLT2i), a mineralocorticoid receptor antagonist (MRA), an endothelin receptor antagonists (ERA) or a glucagon-like peptide- 1 receptor agonist (GLP-1RA).

14. The method of any one of claims 1-13, wherein the patient prior to treatment has proteinuria with a urine protein : creatinine ratio (UPCR) of greater than 1 mg / mg.

15. The method of any one of claims 1-14, wherein the patient prior to treatment has reduced kidney function compared to a healthy subject, as determined by estimated glomerular flow rate (eGFR).

16. The method of claim 15, wherein the patient prior to treatment has an eGFR of about 30 ml / min / 1.73m2or higher.

17. The method of any one of claims 1-16, wherein the administration reduces the amount of proteinuria compared to baseline before the start of treatment.

18. The method of claim 17, wherein the proteinuria is reduced by at least 10%, at least 20%, at least 25%, at least 30%, at least 35%, or at least 40% compared to the baseline.

19. The method of claim 17 or claim 18, wherein the proteinuria is determined based on a measure of mg protein / L urine.

20. The method of claim 17 or claim 18, wherein the proteinuria is determined based on a urine protein : creatinine ratio (UPCR).

21. The method of claim 17 or claim 18, wherein the proteinuria is determined based on a urine albumin : creatinine ratio (UACR).

22. The method of any one of claims 1-20, wherein the eGFR increases, or is decreased by not more than 10% compared to baseline before the start of treatment.

23. The method of any one of claims 1-22, wherein the administration reduces the amount of the autoantibodies to nephrin in the patient compared to baseline before the start of treatment.

24. The method of claim 23, wherein the one or more autoantibodies are reduced by at least 50%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% compared to before the start of treatment.

25. The method of claim 23, wherein the one or more autoantibodies becomes undetectable to the immunological assay in the patient after the administration.

26. The method of any one claims 1-25, wherein the TACI-Ig fusion molecule is administered weekly.120324900938Attorney Docket No.: VETH-016 / 01WO 327083-243127. The method of to claim 26, wherein the TACI-Ig fusion molecule is administered at a dose of between about 75 mg / week and about 150 mg / week.

28. The method of to claim 26, wherein the TACI-Ig fusion molecule is administered at a dose of about 75 mg / week or about 150 mg / week.

29. The method of any one of claims 1-25, wherein the TACI-Ig fusion molecule is administered monthly.

30. The method of claim 29, wherein the TACI-Ig fusion molecule is administered at a dose of between about 300 mg / month and about 600 mg / month.

31. The method of claim 30, wherein the TACI-Ig fusion molecule is administered at a dose of about 300 mg / month, about 450 mg / month, or about 600 mg / month.

32. The method of any one of claims 1-31, wherein the TACI-Ig fusion molecule is administered for at least 6 weeks, at least 12 weeks, at least 24 weeks, at least 36 weeks, at least 48 weeks, at least 52 weeks, at least 72 weeks, at least 96 weeks, at least 108 weeks, at least 3 years, at least 5 years, or at least 10 years.

33. The method of any one of claims 1-32, wherein the TACI-Ig fusion molecule is administered chronically.

34. The method of any one of claims 1-33, wherein the TACI-Ig fusion molecule is administered subcutaneously.

35. The method of any one claims 1-34, wherein the TACI extracellular domain has an amino acid sequence set forth in SEQ ID NO: 1, or an amino acid sequence that is at least 80% identical thereto.

36. The method of claim 35, wherein the human immunoglobulin-constant domain has an amino acid sequence set forth in SEQ ID NO: 2, or an amino acid sequence that is at least 80% identical thereto.

37. The method of any one claims 1-34, wherein the TACI-Ig fusion molecule has an amino acid sequence set forth in SEQ ID NO: 3, or an amino acid sequence that is at least 80% identical thereto.

38. The method of any one claims 1-34, wherein the TACI-Ig fusion molecule, wherein the TACI-Ig fusion molecule is atacicept.

39. The method of any one claims 1-34, wherein the TACI-Ig fusion molecule has an amino acid sequence set forth in any one of SEQ ID NOS: 4-9 and 12, an amino acid sequence that is at least 80% identical thereto.121324900938Attorney Docket No.: VETH-016 / 01WO 327083-243140. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein the TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the patient has a detectable presence of autoantibodies to nephrin as measured in an immunological assay.

41. Use of a transmembrane activator and calcium modulator and cyclophilin ligand- interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein the TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, in the manufacture of a medicament for treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the B-cell responsive autoimmune glomerulopathy is characterized by a detectable presence of autoantibodies to nephrin as measured in an immunological assay.

42. A method of treating a human patient having a B-cell responsive autoimmune glomerulopathy, the method comprising administering to the patient in need thereof an effective amount of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein the TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, wherein the patient has a detectable presence of autoantibodies to phospholipase A2 receptor (PLA2R) or autoantibodies to thrombospondin type 1 domain containing 7A (THSD7A) as measured in an immunological assay.

43. The method of claim 42, wherein the detectable presence of the autoantibodies is a detectable presence in a serum sample or a kidney biopsy sample of the patient.122324900938Attorney Docket No.: VETH-016 / 01WO 327083-243144. The method of claim 42 or claim 43, wherein the B-cell responsive autoimmune glomerulopathy is primary membranous nephropathy (pMN).

45. The method of any one of claims 42-44, wherein the patient is > 18 years of age.

46. The method of any one of claims 42-45, wherein the patient has been on a regimen of another therapeutic agent, prior to treatment with the TACI-Ig fusion molecule.

47. The method of claim 46, wherein the patient remains on the regimen of the another therapeutic agent during treatment with the TACI-Ig fusion molecule.

48. The method of any one of claims 42-47, wherein the patient is placed on a regimen of another therapeutic agent concomitantly with treatment with the TACI-Ig fusion molecule.

49. The method of any one of claims 46-48, wherein the another therapeutic agent is a renin- angiotensin-aldosterone system inhibitor (RAASi).

50. The method of claim 49, wherein the RAASi is an angiotensin converting enzyme inhibitor (ACEi) and / or angiotensin II receptor blocker (ARB).

51. The method of any one of claims 46-48, wherein the another therapeutic agent is a sodium-glucose cotransporter-2 inhibitors (SGLT2i), a mineralocorticoid receptor antagonist (MRA), an endothelin receptor antagonists (ERA) or a glucagon-like peptide- 1 receptor agonist (GLP-1RA).

52. The method of any one of claims 42-51, wherein the patient prior to treatment has proteinuria with a urine protein : creatinine ratio (UPCR) of greater than 1 mg / mg, assessed by urine specimens from 24-hour urine collection.

53. The method of any one of claims 42-52, wherein the patient prior to treatment has reduced kidney function compared to a healthy subject, as determined by estimated glomerular flow rate (eGFR).

54. The method of claim 53, wherein the patient prior to treatment has an eGFR of about 30 ml / min / 1.73m2or higher.

55. The method of any one of claims 42-54, wherein the administration reduces the amount of proteinuria compared to baseline before the start of treatment.

56. The method of claim 55, wherein the proteinuria is reduced by at least 10%, at least 20%, at least 25%, at least 30%, at least 35%, or at least 40% compared to the baseline.

57. The method of claim 55 or claim 56, wherein the proteinuria is determined based on a measure of mg protein / L urine.123324900938Attorney Docket No.: VETH-016 / 01WO 327083-243158. The method of claim 55 or claim 56, wherein the proteinuria is determined based on a urine protein : creatinine ratio (UPCR).

59. The method of claim 55 or claim 56, wherein the proteinuria is determined based on a urine albumin : creatinine ratio (UACR).

60. The method of any one of claims 42-58, wherein the eGFR increases, or is decreased by not more than 10% compared to baseline before the start of treatment.

61. The method of any one of claims 42-60, wherein the administration reduces the amount of the autoantibodies to nephrin in the patient compared to baseline before the start of treatment.

62. The method of claim 61, wherein the one or more autoantibodies are reduced by at least 50%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% compared to before the start of treatment.

63. The method of claim 61, wherein the one or more autoantibodies becomes undetectable to the immunological assay in the patient after the administration.

64. The method of any one claims 42-63, wherein the TACI-Ig fusion molecule is administered weekly.

65. The method of to claim 64, wherein the TACI-Ig fusion molecule is administered at a dose of between about 75 mg / week and about 150 mg / week.

66. The method of to claim 65, wherein the TACI-Ig fusion molecule is administered at a dose of about 75 mg / week or about 150 mg / week.

67. The method of any one of claims 42-63, wherein the TACI-Ig fusion molecule is administered monthly.

68. The method of claim 67, wherein the TACI-Ig fusion molecule is administered at a dose of between about 300 mg / month and about 600 mg / month.

69. The method of claim 68, wherein the TACI-Ig fusion molecule is administered at a dose of about 300 mg / month, about 450 mg / month, or about 600 mg / month.

70. The method of any one of claims 64-69, wherein the TACI-Ig fusion molecule is administered for at least 6 weeks, at least 12 weeks, at least 24 weeks, at least 36 weeks, at least 48 weeks, at least 52 weeks, at least 72 weeks, at least 96 weeks, at least 108 weeks, at least 3 years, at least 5 years, or at least 10 years.

71. The method of any one of claims 42-70, wherein the TACI-Ig fusion molecule is administered chronically.124324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431'll. The method of any one of claims 42-71, wherein the TACI-Ig fusion molecule is administered subcutaneously.

73. The method of any one claims 42-72, wherein the TACI extracellular domain has an amino acid sequence set forth in SEQ ID NO: 1, or an amino acid sequence that is at least 80% identical thereto.

74. The method of claim 73, wherein the human immunoglobulin-constant domain has an amino acid sequence set forth in SEQ ID NO: 2, or an amino acid sequence that is at least 80% identical thereto.

75. The method of any one claims 42-72, wherein the TACI-Ig fusion molecule has an amino acid sequence set forth in SEQ ID NO: 3, or an amino acid sequence that is at least 80% identical thereto.

76. The method of any one claims 42-72, wherein the TACI-Ig fusion molecule, wherein the TACI-Ig fusion molecule is atacicept.

77. The method of any one claims 42-72, wherein the TACI-Ig fusion molecule has an amino acid sequence set forth in any one of SEQ ID NOS: 4-9 and 12, an amino acid sequence that is at least 80% identical thereto.

78. A transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein the TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain, for use in treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the patient has a detectable presence of autoantibodies to PLA2R or autoantibodies to THSD7A as measured in an immunological assay.

79. Use of a transmembrane activator and calcium modulator and cyclophilin ligand- interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein the TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain,125324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 in the manufacture of a medicament for treating a patient having a B-cell responsive autoimmune glomerulopathy in need thereof, wherein the patient has a detectable presence of autoantibodies to PLA2R or autoantibodies to THSD7A as measured in an immunological assay.

80. A method of characterizing a B-cell responsive autoimmune glomerulopathy from a plurality of human patients, the method comprising: a. administering, to the plurality of patients having a kidney disease suspected of being a B-cell responsive autoimmune glomerulopathy, a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain; b. assessing kidney function of the patient after a round of treatment; c. selecting from the plurality of patients a patient that demonstrates improved kidney function after the round of treatment; and d. collecting a serum sample from the selected patient.

81. The method of claim 80, wherein the method further comprises: e. assaying the serum sample for detection of an autoantibody against a protein that is expressed by a kidney cell; and f. characterizing the B-cell responsive autoimmune glomerulopathy of the selected patient based on the detected auto-antibody.

82. The method of claim 81, wherein the kidney cell is a podocyte, glomerular epithelial cell, or a glomerular mesangial cell.

83. A method of determining a course of treatment for a kidney disease, the method comprising: a. administering to a plurality of human patients having a kidney disease suspected of being a B-cell responsive autoimmune glomerulopathy, a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain;126324900938Attorney Docket No.: VETH-016 / 01WO 327083-2431 b. assessing kidney function of the patient after a round of treatment; c. selecting from the plurality of patients a patient that demonstrates improved kidney function after the round of treatment; and d. continuing the administration of the TACI-Ig fusion molecule to the patient.

84. A method of identifying a clinical trial candidate for a B-cell responsive autoimmune glomerulopathy, the method comprising: a. administering to a plurality of patients having a glomerulopathy suspected of being a B-cell responsive autoimmune glomerulopathy a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI)-immunoglobulin (Ig) fusion molecule, wherein said TACI-Ig fusion molecule comprises:(i) a TACI extracellular domain or fragment thereof which binds BAFF (B-cell activating factor) and / or APRIL (A Proliferation-Inducing Ligand); and(ii) a human immunoglobulin-constant domain; b. assessing kidney function of the plurality of patients after a round of treatment; c. selecting from the plurality of patients a patient that demonstrates improved kidney function after the round of treatment; and d. designating the patient as a clinical trial candidate.

85. The method of claim 84, wherein the method further comprises: e. collecting a serum sample from the clinical trial candidate.

86. The method of claim 85, wherein the method further comprises: f. assaying the serum sample for detection of an autoantibody against a protein that is expressed by a kidney cell; g. selecting a clinical trial for a B-cell responsive autoimmune glomerulopathy patient based on the detected autoantibody; h. designating the clinical trial candidate as a clinical trial participant for the selected clinical trial.

87. The method of claim 86, wherein the method further comprising having the clinical trial candidate participate in a clinical trial for the B-cell responsive autoimmune glomerulopathy.

88. The method of any one of claims 80-87, wherein the TACI-Ig fusion molecule is administered weekly.

89. The method of claim 88, wherein the TACI-Ig fusion molecule is administered at a dose of between about 75 mg / week and about 150 mg / week.127324900938Attorney Docket No.: VETH-016 / 01WO 327083-243190. The method of any one of claims 80-87, wherein the TACI-Ig fusion molecule is administered monthly.

91. The method of claim 90, wherein the TACI-Ig fusion molecule or atacicept is administered at a dose of between about 300 mg / month and about 600 mg / month.

92. The method of any one of claims 80-91, wherein the round of treatment is about 2 weeks, about 3 weeks, about 4 weeks, about 5 weeks, about 6 weeks, about 8 weeks, or about 10 weeks.

93. The method of any one of claims 86, and 87, wherein the detected autoantibody is an anti-PLA2R antibody or an anti- THSD7A antibody.

94. The method of claim 93, wherein the B-cell responsive autoimmune glomerulopathy is primary membranous nephropathy (pMN).

95. The method of any one of claims 86, and 87, wherein the auto-antibody is an anti- nephrin antibody.

96. The method of claim 95, wherein the B-cell responsive autoimmune glomerulopathy is primary minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS).

97. The method of any one of claims 80-96, wherein the kidney function is assessed by obtaining a measure of: proteinuria, hematuria, eGFR, or a combination thereof.

98. The method of any one of claim 80-97, wherein the TACI extracellular domain or fragment thereof binds BAFF and APRIL.

99. The method of any one of claim 80-98, wherein said TACI-Ig fusion molecule has an amino acid sequence set forth in any one of SEQ ID NOS: 3-9 and 12, or an amino acid sequence that is at least 80% identical thereto.

100. The method according to any one of claims 80-99, wherein said TACI-Ig fusion molecule is atacicept.128324900938

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