Methods for treating lupus nephritis using FcRn antagonists

Abstract

Provided herein are methods for treating lupus nephritis using an effective amount of a human neonatal Fc receptor (FcRn) antagonist. Also provided herein are FcRn antagonists for use in treating lupus nephritis, and FcRn antagonists for use in the manufacture of medicaments for treating lupus nephritis.

Description

[Technical Field]

[0001] Related Applications This application claims priority to U.S. Provisional Patent Application No. 63 / 382,566, filed November 7, 2022, the entire disclosure of each of which is incorporated herein by reference.

[0002] Sequence Listing Reference This application contains a Sequence Listing, which has been submitted electronically in ST.26 format and is incorporated herein by reference in its entirety (a copy of said ST.26, created on November 6, 2023, is designated "205806_SL.xml" and is 40,649 bytes in size).

[0003] The present disclosure relates to methods of treating lupus nephritis (LN), which in certain embodiments involve the use of an antagonist of the human neonatal Fc receptor (FcRn), efgartigimod. [Background technology]

[0004] It is estimated that over 2.5% of the human population is affected by autoantibody-driven autoimmune diseases in which autoreactive antibodies are directly pathogenic. Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease. LN is an inflammatory autoimmune disease of the kidney caused by SLE and is the most common and life-threatening manifestation of SLE.

[0005] In unselected patients with SLE, approximately 25% to 50% have signs or symptoms of kidney disease at the time of SLE onset, and approximately 40% to 60% of patients with SLE develop kidney complications during the course of the disease. In China, approximately half of patients with SLE have kidney complications.

[0006] In actively proliferating LN, induction therapy with mycophenolate mofetil (MMF) or mycophenolic acid (MPA) or low-dose intravenous (IV) cyclophosphamide (CYC), both combined with glucocorticoids, is recommended. Alternative regimens include treatment with MMF and calcineurin inhibitors (e.g., tacrolimus) and high-dose CYC. Subsequent maintenance therapy includes treatment with MMF or azathioprine without or with low-dose glucocorticoids. Despite aggressive immunosuppressive therapy, 10% to 30% of patients with LN still progress to end-stage renal disease (ESRD), the ultimate manifestation of LN. Furthermore, up to 60% of patients fail to achieve treatment goals with currently available treatment options.

[0007] Therefore, there is a need in the art for improved LN treatment options.

[0008] Therapeutic antagonism of FcRn, a major histocompatibility complex class I-like molecule involved in immunoglobulin G (IgG) recycling and therefore responsible for the long half-life of IgG, is being explored as a strategy to treat IgG-mediated autoimmune diseases, such as generalized myasthenia gravis (gMG), immune thrombocytopenia (ITP), and pemphigus (pemphigus vulgaris (PV) and pemphigus foliaceus (PF)). The remarkable clinical efficacy of FcRn antagonism appears to be directly related to the early clearance of pathogenic IgG autoantibodies from the circulation.

[0009] Pathogenic autoantibodies and complement deposition are important contributors to the pathogenesis of SLE, particularly in LN, where renal deposition of immune complexes is a hallmark of the disease. By reducing accumulated pathogenic autoantibodies in the renal glomeruli, FcRn antagonists may provide a safer and more effective treatment option for patients with LN. Summary of the Invention

[0010] The present disclosure is broadly directed to methods for treating lupus nephritis with FcRn antagonists.

[0011] The present disclosure provides a method of treating lupus nephritis in a subject in need thereof, comprising administering to the subject an effective amount of a human neonatal Fc receptor (FcRn) antagonist. In some embodiments, the FcRn antagonist comprises two, three, or four FcRn-binding regions. In some embodiments, the FcRn antagonist comprises or consists of a variant Fc region or an FcRn-binding fragment thereof. In some embodiments, the variant Fc region or FcRn-binding fragment thereof binds to FcRn with higher affinity at pH 6.0 compared to the corresponding wild-type Fc region. In some embodiments, the variant Fc region or FcRn-binding fragment thereof binds to FcRn with higher affinity at pH 7.4 compared to the corresponding wild-type Fc region.

[0012] In some embodiments, the variant Fc region comprises or consists of a first Fc domain and a second Fc domain that form a homodimer or heterodimer. In some embodiments, the first Fc domain and / or the second Fc domain comprises amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively. In some embodiments, the first Fc domain and / or the second Fc domain comprises amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0013] In some embodiments, the first Fc domain and / or the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 30. In some embodiments, the first Fc domain and the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 30. In some embodiments, the FcRn antagonist is efgartigimod.

[0014] In some embodiments, the FcRn antagonist is an anti-FcRn antibody.

[0015] In some embodiments, the FcRn antagonist is administered to a subject at a fixed dose of 20 mg to 20,000 mg, or at a dose of 0.2 mg / kg to 200 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 10 mg / kg to 30 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 10 mg / kg once a week. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 750 mg to 3000 mg once a week, once every two weeks, once every three weeks, once every four weeks, or once a month. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg or 2000 mg once a week or once every two weeks.

[0016] In some embodiments, the FcRn antagonist is administered for 52 weeks or less. In some embodiments, the FcRn antagonist is administered for 24 weeks or less. In some embodiments, the FcRn antagonist is administered for 24 weeks. In some embodiments, the FcRn antagonist is administered for at least 24 weeks. In some embodiments, the FcRn antagonist is administered for at least 52 weeks.

[0017] In some embodiments, the method also includes administering to the subject an effective amount of a glucocorticoid, mycophenolate mofetil (MMF), mycophenolic acid (MPA), an angiotensin-converting enzyme inhibitor (ACEi), an angiotensin receptor blocker (ARB), hydroxychloroquine, a B-lymphocyte targeting agent, or any combination thereof.

[0018] In some embodiments, the glucocorticoid is methylprednisolone. In some embodiments, methylprednisolone is administered intravenously at a dose of 250 mg to 500 mg once daily. In some embodiments, methylprednisolone is administered daily for 1 to 3 days. In some embodiments, methylprednisolone is administered for 3 days.

[0019] In some embodiments, the glucocorticoid is prednisone. In some embodiments, prednisone is orally administered at a dose of 10 mg / day to 60 mg / day. In some embodiments, prednisone is orally administered at a dose of 0.5 mg / kg / day to 1 mg / kg / day. In some embodiments, when the subject is administered an FcRn antagonist, the dose of prednisone is tapered to a dose of 7.5 mg / day over 12 weeks.

[0020] In some embodiments, MMF or MPA is administered daily, hi some embodiments, MMF or MPA is administered in a daily dose, with the daily dose being up-titrated to 1.5 g / day to 2 g / day in divided doses within 4 weeks.

[0021] In some embodiments, hydroxychloroquine is administered at a dose of up to 5 mg / kg / day. In some embodiments, hydroxychloroquine is administered for 24 weeks. In some embodiments, hydroxychloroquine is administered for at least 24 weeks.

[0022] In some embodiments, the B lymphocyte targeting agent is selected from the group consisting of belimumab, rituximab, and obinutuzumab.

[0023] The present disclosure also provides a method of treating lupus nephritis in a subject in need thereof, comprising administering to the subject an effective amount of an FcRn antagonist within 60 days of the subject receiving induction therapy for lupus nephritis. In some embodiments, the induction therapy comprises administering to the subject an effective amount of a glucocorticoid.

[0024] In some embodiments, induction therapy comprises administering to the subject an effective amount of methylprednisolone. In some embodiments, methylprednisolone is administered intravenously at a dose of 250 mg to 500 mg once daily. In some embodiments, methylprednisolone is administered daily for 1 to 3 days. In some embodiments, methylprednisolone is administered for 3 days.

[0025] In some embodiments, the induction therapy comprises administering prednisone to the subject. In some embodiments, the prednisone is administered orally at a dose of 10 mg / day to 60 mg / day. In some embodiments, the prednisone is administered orally at a dose of 0.5 mg / kg / day to 1 mg / kg / day. In some embodiments, when the subject is administered the FcRn antagonist, the dose of prednisone is tapered to a dose of 7.5 mg / day over 12 weeks.

[0026] In some embodiments, the induction therapy further comprises administering to the subject a daily dose of an effective amount of MMF or MPA, hi some embodiments, the daily dose of MMF or MPA is up-titrated to 1.5 g / day to 2 g / day in divided doses within 4 weeks.

[0027] In some embodiments, the induction therapy also includes administering to the subject an effective dose of hydroxychloroquine. In some embodiments, the dose of hydroxychloroquine is up to 5 mg / kg / day. In some embodiments, the hydroxychloroquine is administered for 24 weeks. In some embodiments, the dose of hydroxychloroquine is administered for at least 24 weeks.

[0028] In some embodiments, the induction therapy also comprises administering to the subject an effective amount of a B-lymphocyte targeting agent, hi some embodiments, the B-lymphocyte targeting agent is selected from the group consisting of belimumab, rituximab, and obinutuzumab.

[0029] In some embodiments, after administering the FcRn antagonist to the subject, the subject has a blood flow of at least 60 mL / min / 1.73 m 2 In some embodiments, after administering an FcRn antagonist to the subject, the subject exhibits a post-administration estimated glomerular filtration rate (eGFR) that is reduced by less than 20% compared to a baseline eGFR obtained from the subject prior to administering the FcRn antagonist. In some embodiments, the post-administration eGFR is measured 24 or 52 weeks after administering the FcRn antagonist to the subject. In some embodiments, after administering the FcRn antagonist to the subject, the subject exhibits a post-administration eGFR of at least 90 mL / min / 1.73 m 2 In some embodiments, after administering an FcRn antagonist to the subject, the subject exhibits a post-administration eGFR that is reduced by less than 10% compared to a baseline eGFR obtained from the subject prior to administration of the FcRn antagonist. In some embodiments, the post-administration eGFR is measured 24 or 52 weeks after administering the FcRn antagonist to the subject.

[0030] In some embodiments, after administering the FcRn antagonist to the subject, the subject exhibits a post-administration urinary protein creatinine ratio (UPCR) of at most 0.5 mg / mg. In some embodiments, after administering the FcRn antagonist to the subject, the subject exhibits a post-administration UPCR that is reduced by at least 50% compared to a baseline UPCR obtained from the subject before administering the FcRn antagonist, and if the baseline UPCR is at most 3 mg / mg, the post-administration UPCR is less than 1 mg / mg. In some embodiments, after administering the FcRn antagonist to the subject, the subject exhibits a post-administration UPCR that is reduced by at least 50% compared to a baseline UPCR obtained from the subject before administering the FcRn antagonist, and if the baseline UPCR is more than 3 mg / mg, the post-administration UPCR is less than 3 mg / mg. In some embodiments, the post-administration UPCR is measured 24 or 52 weeks after administering the FcRn antagonist to the subject.

[0031] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a reduced post-administration Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K score compared to a baseline SLEDAI-2K score obtained from the subject before administering the FcRn antagonist. In some embodiments, the post-administration SLEDAI-2K score is measured 24 or 52 weeks after administering the FcRn antagonist to the subject.

[0032] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post-administration level of serum autoantibodies that is reduced compared to the baseline level of serum autoantibodies obtained from the subject before administering the FcRn antagonist. In some embodiments, the post-administration level of serum autoantibodies is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% compared to the baseline level of serum autoantibodies obtained from the subject before administering the FcRn antagonist. In some embodiments, the post-administration level of serum autoantibodies is measured 24 or 52 weeks after administering the FcRn antagonist to the subject. In some embodiments, the serum autoantibody is selected from the group consisting of anti-dsDNA, ANA, aCL, anti-Sm, and anti-C1q.

[0033] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post-administration level of serum complement that is reduced compared to a baseline level of serum complement obtained from the subject before administering the FcRn antagonist. In some embodiments, the post-administration level of serum complement is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% compared to a baseline level of serum complement obtained from the subject before administering the FcRn antagonist. In some embodiments, the post-administration level of serum complement is measured 24 or 52 weeks after administering the FcRn antagonist to the subject. In some embodiments, the serum complement is selected from the group consisting of C3, C4, CH50, and C1q-bound circulating immune complexes.

[0034] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post-administration level of serum IgG that is reduced compared to the baseline level of serum IgG obtained from the subject before administering the FcRn antagonist. In some embodiments, the post-administration level of serum IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% compared to the baseline level of serum IgG obtained from the subject before administering the FcRn antagonist. In some embodiments, the post-administration level of serum IgG is measured 24 or 52 weeks after administering the FcRn antagonist to the subject.

[0035] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post-administration level of serum albumin that is not reduced compared to the baseline level of serum albumin obtained from the subject before administering the FcRn antagonist.

[0036] In some embodiments, the FcRn antagonist is in an aqueous solution comprising about 4 mM sodium phosphate, about 146 mM sodium chloride, about 24 mM L-arginine, and about 0.0032% (w / v) polysorbate 80, and the composition has a pH of about 6.7. In some embodiments, the aqueous solution comprises about 3.2 mg / ml of the FcRn antagonist.

[0037] In some embodiments, the FcRn antagonist is in an aqueous solution comprising about 20 mM L-histidine, about 100 mM sodium chloride, about 60 mM sucrose, about 10 mM L-methionine, and about 0.04% (w / v) polysorbate 20, and the composition has a pH of about 6.0. In some embodiments, the aqueous solution comprises about 180 mg / ml of the FcRn antagonist.

[0038] In some embodiments, the FcRn antagonist is in an aqueous solution comprising about 20 mM L-histidine, about 50 mM L-arginine, about 100 mM sodium chloride, about 60 mM sucrose, about 10 mM L-methionine, and about 0.04% (w / v) polysorbate 80, and the composition has a pH of about 6.0. In some embodiments, the aqueous solution comprises about 200 mg / ml of the FcRn antagonist.

[0039] The present disclosure also provides an FcRn antagonist for use in the treatment of lupus nephritis, wherein treatment is carried out by the methods described above and herein.

[0040] The present disclosure also provides an FcRn antagonist for use in the manufacture of a medicament for the treatment of lupus nephritis, wherein treatment is carried out by the methods described above and herein.

[0041] The present disclosure also provides the use of an FcRn antagonist for the treatment of lupus nephritis according to the methods described above and herein.

[0042] The present disclosure also provides the use of an FcRn antagonist for the manufacture of a medicament for the treatment of lupus nephritis, wherein the treatment is carried out by the methods described above and herein. [Brief explanation of the drawings]

[0043] [Figure 1]

[0023] Figure 1 is a set of graphs showing IgG circulating immune complex (IgG CIC) levels (upper panel) and disease severity (lower panel) in human subjects with pemphigus vulgaris (PV; n=6) and pemphigus foliaceus (PF; n=6) after efgartigimod treatment. The black line indicates the median. The dotted line indicates CS (clinical significance). PDAI: Pemphigus Disease Area Index; CR: Complete Clinical Remission; EoT: End of Treatment; EoS: End of Study. The data demonstrate that efgartigimod reduced circulating immune complex levels. DETAILED DESCRIPTION OF THE INVENTION

[0044] The present disclosure provides engineered FcRn antagonists and methods for their use in the treatment of LN. Advantageously, the methods disclosed herein allow for long-term maintenance of kidney function, prevention of disease flares, prevention of organ damage, management of comorbidities, improvement in patient survival, and improvement in disease-related quality of life.

[0045] definition As used herein, the term "FcRn" refers to neonatal Fc receptor. Exemplary FcRn molecules include human FcRn, encoded by the FCGRT gene as shown in RefSeq NM 004107. The amino acid sequence of the corresponding protein is shown in RefSeq NP_004098.

[0046] As used herein, the term "FcRn antagonist" refers to any agent that specifically binds to FcRn and inhibits the binding of an immunoglobulin to FcRn (e.g., human FcRn). In one embodiment, the FcRn antagonist is an Fc region (e.g., a variant Fc region disclosed herein) that specifically binds to FcRn via the Fc region and inhibits the binding of an immunoglobulin to FcRn. In one embodiment, the FcRn antagonist is not a full-length IgG antibody. In one embodiment, the FcRn antagonist comprises an antigen-binding site that binds to a target antigen and a variant Fc region. In one embodiment, the FcRn antagonist is an Fc fragment that comprises or consists of an Fc region and lacks the antigen-binding site. In one embodiment, the term "FcRn antagonist" refers to an antibody or antigen-binding fragment thereof that specifically binds to FcRn via its antigen-binding domain or its Fc region and inhibits the binding of the Fc region of an immunoglobulin (e.g., an IgG autoantibody) to FcRn.

[0047] As used herein, the terms "antibody" and "antibodies" include full-length antibodies, antigen-binding fragments of full-length antibodies, and molecules comprising an antibody CDR, VH region, or VL region. Examples of antibodies include monoclonal antibodies, recombinantly produced antibodies, monospecific antibodies, multispecific antibodies (including bispecific antibodies), human antibodies, humanized antibodies, chimeric antibodies, immunoglobulins, synthetic antibodies, tetrameric antibodies comprising two heavy chain and two light chain molecules, antibody light chain monomers, antibody heavy chain monomers, antibody light chain dimers, antibody heavy chain dimers, antibody light chain-antibody heavy chain pairs, intrabodies, heteroconjugate antibodies, antibody-drug conjugates, single domain antibodies (sdAbs), monovalent antibodies, single chain antibodies or single chain Fvs (scFvs), camelid antibodies, affibody molecules, humanized antibodies, VHH fragments, Fab fragments, F(ab')2 fragments, disulfide-linked Fvs (sdFvs), anti-idiotypic (anti-Id) antibodies (including, for example, anti-anti-Id antibodies), and antigen-binding fragments of any of the above. An antibody may be any type (e.g., IgG, IgE, IgM, IgD, IgA, or IgY), any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, or IgA2), or any subclass (e.g., IgG 2a or IgG 2b ) can be.

[0048] As used herein, the term "Fc domain" refers to the portion of a single immunoglobulin heavy chain that comprises both the CH2 and CH3 domains of an antibody. In some embodiments, the Fc domain comprises at least a portion of the hinge (e.g., upper, middle, and / or lower hinge regions), the CH2 domain, and the CH3 domain. In some embodiments, the Fc domain does not comprise the hinge region.

[0049] As used herein, the term "hinge region" refers to the portion of a heavy chain molecule that connects the CH1 domain to the CH2 domain. In some embodiments, the hinge region is up to 70 amino acid residues in length. In some embodiments, the hinge region comprises approximately 25 amino acid residues and is flexible, thereby allowing the two N-terminal antigen-binding regions to move independently. In some embodiments, the hinge region comprises approximately 11-17 amino acid residues and is flexible, thereby allowing the two N-terminal antigen-binding regions to move independently. In some embodiments, the hinge region is 12 amino acid residues in length. In some embodiments, the hinge region is 15 amino acid residues in length. In some embodiments, the hinge region is 62 amino acid residues in length. The hinge region can be subdivided into three distinct domains: the upper, middle, and lower hinge domains. The FcRn antagonists of the present disclosure can comprise all or any portion of the hinge region. In some embodiments, the hinge region is derived from an IgG1 antibody. In some embodiments, the hinge region comprises the amino acid sequence EPKSCDKTHTCPPCP (SEQ ID NO: 12).

[0050] As used herein, the term "Fc region" refers to the portion of an immunoglobulin formed by the Fc domains of its two heavy chains. The Fc region can be a wild-type Fc region (native Fc region) or a variant Fc region. A native Fc region is a homodimer. The Fc region can be derived from any naturally occurring immunoglobulin. In some embodiments, it is formed from an IgA, IgD, IgE, or IgG heavy chain constant region. In some embodiments, the Fc region is formed from an IgG heavy chain constant region. In some embodiments, the IgG heavy chain is an IgG1, IgG2, IgG3, or IgG4 heavy chain constant region. In some embodiments, the Fc region is formed from an IgG1 heavy chain constant region. In some embodiments, the IgG1 heavy chain constant region comprises the G1m1(a), G1m2(x), G1m3(f), or G1m17(z) allotype. See, e.g., Jefferis and Lefranc (2009) mAbs 1(4):332-338, and de Taeye et al. (2020) Front Immunol. 11:740, which are incorporated by reference in their entireties.

[0051] As used herein, the term "variant Fc region" refers to an Fc region having one or more modifications relative to a native Fc region. Modifications can include amino acid substitutions, additions and / or deletions, attachment of additional moieties, and / or modifications of native glycans. The term encompasses heterodimeric Fc regions in which each of the constituent Fc domains is different. The term also encompasses single-chain Fc regions in which the constituent Fc domains are linked together by linker moieties.

[0052] As used herein, the term "FcRn-binding fragment" refers to a portion of an Fc region sufficient to confer FcRn binding.

[0053] As used herein, the term "EU position" refers to an amino acid position in the EU numbering system for the Fc region as described in Edelman, GM et al., Proc. Natl. Acad. USA, 63, 78-85 (1969), and Rabat et al., "Sequences of Proteins of Immunological Interest," USDept. Health and Human Services, 5th edition, 1991.

[0054] As used herein, the term "baseline" refers to a measurement (e.g., B cell frequency, IgG level) in a patient, e.g., a patient's blood or urine, prior to the first administration (e.g., intravenous or subcutaneous administration) of a therapy (e.g., an FcRn antagonist).

[0055] As used herein, the term "autoantibody-mediated disease" refers to any disease or disorder in which the underlying pathology is caused, at least in part, by pathogenic IgG autoantibodies.

[0056] As used herein, the terms "treat," "treating," and "treatment" refer to therapeutic or prophylactic measures as described herein. Methods of "treatment" employ administering a polypeptide to a subject having or susceptible to a disease or disorder to prevent, cure, delay, reduce the severity of, or ameliorate a disease or disorder, or one or more symptoms of a recurrent disease or disorder, or to prolong the subject's survival beyond that expected in the absence of such treatment.

[0057] As used herein, in the context of administering therapy, the term "effective amount" refers to the amount of therapy that achieves the desired prophylactic or therapeutic effect.

[0058] As used herein, the term "dose" or "dosage" refers to the amount of a drug administered to a subject in a single administration.

[0059] As used herein, the terms "fixed dose" or "flat dose" both refer to a dose that does not vary based on subject characteristics (e.g., weight, e.g., within a set range; sex; age, e.g., within a set range, etc.).

[0060] As used herein, the term "remission" refers to a patient who has no new markers of autoantibody-mediated disease and has completely resolved or cured baseline markers of disease.

[0061] As used herein, the term "relapse" or "flare" refers to a patient with an autoantibody-mediated disease who has the appearance of physical symptoms and / or an increase in markers of autoantibody-mediated disease after a period of remission of the autoantibody-mediated disease. In some embodiments, the flare is an LN flare. In some embodiments, an LN flare is characterized by a 20% increase in urinary protein creatinine ratio (UPCR) from baseline. In some embodiments, the flare is an extrarenal SLE flare. In some embodiments, an extrarenal SLE flare is characterized by an increase in SLEDAI-2K score that is not explained by either hypocomplementemia, an increase in anti-dsDNA antibody levels, the initiation of new immunosuppressive therapy, or an increase in corticosteroids.

[0062] As used herein, the term "subject," or "patient," or "participant" includes any human or non-human animal. In one embodiment, the subject, or patient, or participant is a human or non-human mammal. In one embodiment, the subject, or patient, or participant is human. In some embodiments, the human subject, or patient, or participant is of Asian descent.

[0063] As used herein, the terms "about" or "approximately," when referring to a measurable value, such as a dosage, encompass variations of ±20%, ±15%, ±10%, ±5%, ±1%, or ±0.1% of a given value or range, as appropriate for practicing the methods disclosed herein.

[0064] Lupus nephritis Systemic lupus erythematosus (SLE) is a complex, chronic disease that is difficult to diagnose and treat. SLE is a heterogeneous autoimmune disease characterized by dysregulation of T- and B-lineage cells and other components of the innate immune system. A hallmark of the disease is the production of pathogenic autoantibodies against double-stranded DNA (dsDNA), phospholipids, blood cells, and other targets.

[0065] SLE symptoms are associated with multiple autoantibodies that lead to immune complex formation and deposition, as well as other immune processes. LN, an inflammatory autoimmune disease of the kidney caused by SLE, is the most common and life-threatening manifestation of systemic lupus erythematosus (LN). LN is primarily caused by type 3 hypersensitivity reactions, in which anti-double-stranded DNA (anti-dsDNA) binds to DNA, forming anti-dsDNA immune complexes. These immune complexes are deposited in the subendothelial and / or subepithelial spaces of the mesangial glomerular space near the glomerular basement membrane of the kidney. This leads to an inflammatory response and the development of LN, in which the complement pathway is activated with the resulting influx of neutrophils and other inflammatory cells. Approximately 40% to 60% of patients with SLE develop renal complications at some point during the course of SLE disease, resulting in significant morbidity or mortality. Approximately 25% to 50% of patients with SLE already have signs or symptoms of kidney disease at the time of SLE diagnosis. In China, approximately half of patients with SLE have renal complications.

[0066] All patients with LN are considered to have chronic kidney disease (CKD), and in some patients with LN, CKD progresses to end-stage renal disease (ESRD). In China, LN is one of the most common causes of ESRD. Symptoms of LN include blood in the urine, foamy urine, proteinuria, hypertension, edema, arthralgia, myalgia, butterfly rash, and high levels of creatine in the blood.

[0067] LNs are histologically classified into six distinct classes, representing different manifestations and severity of renal complications in SLE. The rationale for classifying LNs into different classes also considers differences in prognosis. Glomerulonephritis is the most common form of renal disease in SLE, but is frequently accompanied by tubulointerstitial and vascular lesions. Generally, LNs with class VI represent renal atrophy in ESRD. Patients with varying degrees of proliferative LNs (class III, IV, or V), but not class I or II LNs, are at immediate risk for CKD progression. These classes represent the most severe manifestations of renal pathology and require aggressive immunosuppressive treatment to prevent progression to ESRD and minimize associated morbidity and mortality.

[0068] The goals of treatment include patient survival, long-term maintenance of kidney function, prevention of disease flares, prevention of organ damage, management of comorbidities, and improvement in disease-related quality of life. The European League Against Rheumatism and the European Renal Association-European Dialysis and Transplant Association (EULAR / ERA-EDTA) recommend initial (induction) treatment with mycophenolate mofetil (MMF, 2 g to 3 g / day, or equivalent doses of mycophenolic acid [MPA]) or low-dose intravenous (IV) cyclophosphamide (CYC; 500 mg × 6 biweekly doses), both in combination with glucocorticoids (IV methylprednisolone pulses, followed by oral prednisone), for actively proliferating LN. MMF / calcineurin inhibitor (CNI) combinations (especially tacrolimus) and high-dose CYC are alternatives for patients with nephrotic-range proteinuria and adverse prognostic factors. Subsequent long-term maintenance treatment with MMF or azathioprine without or with low-dose (<7.5 mg / day) glucocorticoids should follow. Similarly, the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline recommends that for patients with active LN, initial treatment includes corticosteroids (IV methylprednisolone at 0.25 to 0.5 g / day for 1 to 3 days, followed by oral prednisone at 0.6 to 1 mg / kg / day [not to exceed 80 mg / day], tapering to the maintenance dose over several months), and calcineurin inhibitors (e.g., tacrolimus and voclosporin), mycophenolate analogs (e.g., MMF or mycophenolate sodium), and CYC. See KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases, Kidney Intl. (2021) 100(45):S1-S276, which is incorporated herein by reference in its entirety.Additionally, KDIGO recommends initial treatment with B-lymphocyte-targeted biologics, such as, but not limited to, belimumab and rituximab.

[0069] Despite aggressive immunosuppressive therapy, 10% to 30% of patients with LN still progress to ESRD. Although these outcomes have improved over the past 30 years, there remains a continuing risk of treatment failure (defined by death, ESRD, persistent doubling of serum creatinine, LN flare, or need for rescue medication). Because up to 60% of patients fail to achieve treatment goals with current treatment options, there is a clear need for more effective treatments.

[0070] Substantial evidence indicates that an early reduction in proteinuria, particularly within 6 to 12 months of treatment initiation, is the single best predictor of improved long-term outcomes, including reduced risk of disease flares, ESRD, and death. Therefore, proteinuria or UPCR is a useful parameter for assessing treatment efficacy and is a preferred outcome measure by regulatory agencies. An early reduction in UPCR indicates long-term benefit in the treatment of LN.

[0071] FcRn antagonists FcRn antagonists useful in the methods and uses provided herein include any molecule that binds to and inhibits FcRn, including, but not limited to, any anti-FcRn antibody, any anti-FcRn binding region, or any Fc domain or Fc region.

[0072] In some embodiments, the FcRn antagonists disclosed herein comprise two, three, or four FcRn-binding regions, such as Fc regions.

[0073] Any Fc region can be altered to generate a variant Fc region for use in the methods disclosed herein. Generally, the Fc region, or an FcRn-binding fragment thereof, is derived from a human immunoglobulin. However, it is understood that the Fc region can be derived from the immunoglobulin of any other mammalian species, including, for example, Camelidae species, rodents (e.g., mouse, rat, rabbit, guinea pig), or non-human primate (e.g., chimpanzee, macaque) species. Furthermore, the Fc region, or a portion thereof, can be derived from any immunoglobulin class, including IgM, IgG, IgD, IgA, and IgE, and any immunoglobulin isotype, including IgG1, IgG2, IgG3, and IgG4. In one embodiment, the Fc region is an IgG Fc region (e.g., a human IgG region). In one embodiment, the Fc region is an IgG1 Fc region (e.g., a human IgG1 region). In one embodiment, the Fc region is a chimeric Fc region comprising portions of several different Fc regions. Suitable examples of chimeric Fc regions are described in US2011 / 0243966A1, which is incorporated herein by reference in its entirety. Various Fc region gene sequences (e.g., human constant region gene sequences) are available in the form of public deposits.

[0074] The Fc region can be further truncated or internally deleted to generate its minimal FcRn-binding fragment. The ability of the Fc region fragment to bind to FcRn can be determined using any art-recognized binding assay (e.g., ELISA).

[0075] To improve the manufacturability of the FcRn antagonists disclosed herein, the constituent Fc region preferably does not contain any non-disulfide-bonded cysteine ​​residues. Thus, in one embodiment, the Fc region does not contain any free cysteine ​​residues.

[0076] Any Fc variant, or FcRn-binding fragment thereof, that specifically binds to FcRn with increased affinity and reduced pH dependence relative to a native (i.e., wild-type) Fc region can be used in the methods disclosed herein. In one embodiment, the variant Fc region comprises amino acid changes, substitutions, insertions, and / or deletions that confer desired characteristics. In some embodiments, the FcRn antagonist comprises a variant Fc region or an FcRn-binding fragment thereof, which binds to FcRn with higher affinity at pH 5.5 compared to the corresponding wild-type Fc region. In some embodiments, the FcRn antagonist comprises or consists of a variant Fc region or an FcRn-binding fragment thereof that binds to FcRn with higher affinity at pH 6.0 and / or pH 7.4 compared to the corresponding wild-type Fc region. In some embodiments, the FcRn antagonist comprises a variant Fc region or an FcRn-binding fragment thereof that binds to FcRn with higher affinity at both acidic and neutral pH.

[0077] In some embodiments, the variant Fc region is derived from the Fc region of any native immunoglobulin. In some embodiments, the native immunoglobulin is a human immunoglobulin. In some embodiments, the immunoglobulin is IgA, IgD, IgE, or IgG. In some embodiments, the immunoglobulin is IgG. In some embodiments, the immunoglobulin is human IgA, human IgD, human IgE, or human IgG. In some embodiments, the immunoglobulin is human IgG. In some embodiments, the IgG is IgG1, IgG2, IgG3, or IgG4. In some embodiments, the human IgG is human IgG1, human IgG2, human IgG3, or human IgG4. In some embodiments, the variant Fc region is altered from a human IgG1 Fc region. In some embodiments, the human IgG1 Fc region comprises a G1m1(a), G1m2(x), G1m3(f), or G1m17(z) allotype.

[0078] In one embodiment, the variant Fc region, or FcRn-binding fragment thereof, consists of two Fc domains.

[0079] In one embodiment, the variant Fc region comprises or consists of a first Fc domain and a second Fc domain that form a homodimer or heterodimer. In one embodiment, the first Fc domain and / or the second Fc domain comprises amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively. In one embodiment, the first Fc domain and / or the second Fc domain comprises amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0080] In some embodiments, the FcRn antagonist disclosed herein comprises or consists of at least one Fc domain, and the amino acid sequence of the at least one Fc domain comprises or consists of the amino acid sequence of SEQ ID NO: 13, as provided below in Table 1. [Table 1]

[0081] In some embodiments, the FcRn antagonist disclosed herein comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 13.

[0082] In some embodiments, the FcRn antagonist disclosed herein comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 1 to 3 and 14 to 31. In some embodiments, the dimer is a heterodimer or a homodimer. [Table 2] TIFF2025537707000003.tif243170

[0083] In one embodiment, the first Fc domain and / or the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3. In one embodiment, the first Fc domain and the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3.

[0084] In one embodiment, the first Fc domain and / or the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 1, 2, 3, and 30. In one embodiment, the first Fc domain and the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 1, 2, 3, and 30.

[0085] In some embodiments, the FcRn antagonist comprises a population of FcRn antagonist molecules. In some embodiments, the FcRn antagonist comprising a first Fc domain and a second Fc domain comprising amino acid sequences independently selected from the group consisting of SEQ ID NOs: 1, 2, and 3 is the predominant FcRn antagonist molecule in the population of FcRn antagonist molecules. In some embodiments, the FcRn antagonist comprising a first Fc domain and a second Fc domain comprising amino acid sequences independently selected from the group consisting of SEQ ID NOs: 1, 2, 3, and 30 is the predominant FcRn antagonist molecule in the population of FcRn antagonist molecules. In some embodiments, the predominant FcRn antagonist molecules constitute at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the population of FcRn antagonist molecules.

[0086] In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region comprises the amino acid sequence of SEQ ID NO: 1. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 1. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region comprises the amino acid sequence of SEQ ID NO: 2. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 2. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region comprises the amino acid sequence of SEQ ID NO: 3. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 3. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region comprises the amino acid sequence of SEQ ID NO: 30. In one embodiment, the amino acid sequence of the Fc domain of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 30.

[0087] In one embodiment, the FcRn antagonist consists of a variant Fc region, wherein the variant Fc region comprises two Fc domains, wherein the amino acid sequence of each of the Fc domains is independently selected from SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3. In one embodiment, the FcRn antagonist consists of a variant Fc region, wherein the variant Fc region comprises two Fc domains, wherein the amino acid sequence of each of the Fc domains is independently selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 30.

[0088] In certain embodiments, the variant Fc region is a heterodimer, and the constituent Fc domains are different from each other. Methods for generating Fc heterodimers are known in the art (see, e.g., U.S. Pat. No. 8,216,805, incorporated herein by reference in its entirety). In one embodiment, the FcRn antagonist consists of a variant Fc region, wherein the variant Fc region consists of two Fc domains that form a heterodimer, and the amino acid sequence of each Fc domain is independently selected from SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3. In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains that form a heterodimer, and the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3. In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains that form a heterodimer, and the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 2, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3. In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains that form a heterodimer, and the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 3, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2.

[0089] In one embodiment, the FcRn antagonist consists of a variant Fc region, wherein the variant Fc region consists of two Fc domains that form a heterodimer, and the amino acid sequence of each of the Fc domains is independently selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 30. In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains that form a heterodimer, and the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 30. In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains that form a heterodimer, and the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 2, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 3, or SEQ ID NO: 30. In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains that form a heterodimer, and the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 3, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 30. In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains that form a heterodimer, and wherein the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO:30, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, or SEQ ID NO:3.

[0090] In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains that form a homodimer, and the amino acid sequence of each of the Fc domains consists of or comprises the amino acid sequence of SEQ ID NO:1.

[0091] In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains that form a homodimer, and the amino acid sequence of each of the Fc domains consists of or comprises the amino acid sequence of SEQ ID NO:2.

[0092] In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains that form a homodimer, and the amino acid sequence of each of the Fc domains consists of or comprises the amino acid sequence of SEQ ID NO:3.

[0093] In one embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains that form a homodimer, and the amino acid sequence of each of the Fc domains consists of or comprises the amino acid sequence of SEQ ID NO: 30.

[0094] In some embodiments, the FcRn antagonist comprises glycanation in one or both of the Fc domains. In some embodiments, the FcRn antagonist molecule comprises glycanation at EU position 297 in one or both of the Fc domains. In some embodiments, the glycanation comprises an N-glycan. In some embodiments, the N-glycan comprises a G0F N-glycan, a G1F N-glycan, a G2F N-glycan, or a G0 N-glycan.

[0095] In some embodiments, the FcRn antagonist comprises or consists of a population of FcRn antagonists, wherein at least 33%, at least 34%, at least 35%, at least 36%, at least 37%, at least 38%, at least 39%, at least 40%, at least 41%, at least 42%, at least 43%, at least 44%, at least 45%, at least 46%, at least 47%, at least 48%, at least 49%, at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, or at least 57% of the population of Fc domains of the FcRn antagonists comprise galactose. In some embodiments, the population comprises or consists of FcRn antagonists, wherein at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the population of Fc domains of the FcRn antagonists comprise fucose.

[0096] In some embodiments, the FcRn antagonist lacks an amino acid at EU position 441 of one or both Fc domains. In some embodiments, the FcRn antagonist comprises a glycine and a lysine at EU positions 440 and 441, respectively. In some embodiments, the FcRn antagonist lacks amino acids at EU positions 440 and 441. In some embodiments, the FcRn antagonist comprises an amidated proline at EU position 439. In some embodiments, the FcRn antagonist lacks amino acids at EU positions 440 and 441 and comprises an amidated proline at EU position 439.

[0097] In some embodiments, the FcRn antagonist comprises aspartic acid, lysine, threonine, histidine, threonine, and cysteine ​​at EU positions 221, 222, 223, 224, 225, and 226, respectively. In some embodiments, the FcRn antagonist lacks an amino acid at EU position 221 and comprises lysine, threonine, histidine, threonine, and cysteine ​​at EU positions 222, 223, 224, 225, and 226, respectively. In some embodiments, the FcRn antagonist lacks amino acids at EU positions 221 and 222 and comprises threonine, histidine, threonine, and cysteine ​​at EU positions 223, 224, 225, and 226, respectively. In some embodiments, the FcRn antagonist lacks amino acids at EU positions 221-224 and comprises threonine and cysteine, respectively, at EU positions 225 and 226. In some embodiments, the FcRn antagonist lacks amino acids at EU positions 221, 222, 223, 224, 225, and 226.

[0098] In some embodiments, the FcRn antagonist is a population of FcRn antagonist molecules. In some embodiments, the population of FcRn antagonist molecules comprises or consists of multiple subpopulations of FcRn antagonist molecules. In some embodiments, the population of FcRn antagonist molecules comprises or consists of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 subpopulations.

[0099] In some embodiments, a first subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:3.

[0100] In some embodiments, a second subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs: 3 and 22, respectively.

[0101] In some embodiments, a third subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs: 3 and 19, respectively.

[0102] In some embodiments, a fourth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 3, and wherein two asparagine residues in each FcRn antagonist molecule in the fourth subpopulation are deamidated.

[0103] In some embodiments, a fifth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs: 3 and 19, respectively, and one asparagine residue in each FcRn antagonist molecule in the fifth subpopulation is deamidated.

[0104] In some embodiments, a sixth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs: 2 and 3, respectively.

[0105] In some embodiments, a seventh subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs: 2 and 3, respectively, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the seventh subpopulation is oxidized.

[0106] In some embodiments, an eighth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:2.

[0107] In some embodiments, a ninth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs: 3 and 16, respectively.

[0108] In some embodiments, a tenth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs: 2 and 3, respectively, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the tenth subpopulation is oxidized.

[0109] In some embodiments, an eleventh subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 3, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the eleventh subpopulation is oxidized.

[0110] In some embodiments, a first subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO:3.

[0111] In some embodiments, a second subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 3 and 22, respectively.

[0112] In some embodiments, a third subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 3 and 19, respectively.

[0113] In some embodiments, a fourth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 3, and wherein two asparagine residues in each FcRn antagonist molecule in the fourth subpopulation are deamidated.

[0114] In some embodiments, a fifth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 3 and 19, respectively, and one asparagine residue in each FcRn antagonist molecule in the fifth subpopulation is deamidated.

[0115] In some embodiments, a sixth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 2 and 3, respectively.

[0116] In some embodiments, a seventh subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 2 and 3, respectively, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the seventh subpopulation is oxidized.

[0117] In some embodiments, an eighth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO:2.

[0118] In some embodiments, a ninth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 3 and 16, respectively.

[0119] In some embodiments, a tenth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 2 and 3, respectively, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the tenth subpopulation is oxidized.

[0120] In some embodiments, an eleventh subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 3, and one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the eleventh subpopulation is oxidized.

[0121] In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with one of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with two of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with three of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with four of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with five of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with six of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with seven of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with eight of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with nine of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations.In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with all of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations.

[0122] In some embodiments, the population comprises or consists of the first and second subpopulations. In some embodiments, the population comprises or consists of the first and third subpopulations. In some embodiments, the population comprises or consists of the first and fourth subpopulations. In some embodiments, the population comprises or consists of the first and fifth subpopulations. In some embodiments, the population comprises or consists of the first and sixth subpopulations. In some embodiments, the population comprises or consists of the first and seventh subpopulations. In some embodiments, the population comprises or consists of the first and eighth subpopulations. In some embodiments, the population comprises or consists of the first and ninth subpopulations. In some embodiments, the population comprises or consists of the first and tenth subpopulations. In some embodiments, the population comprises or consists of the first and eleventh subpopulations. In some embodiments, the populations listed above further comprise or consist of 1, 2, 3, 4, 5, 6, 7, 8, or 9 additional subpopulations. In some embodiments, these additional subpopulations are one or more of those described above.

[0123] In some embodiments, the population comprises or consists of subpopulations 1 and 7, 9, or 11. In some embodiments, the population comprises or consists of subpopulations 1, 7, 9, and 11.

[0124] In some embodiments, the first subpopulation constitutes at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, or at least 90% of the population of FcRn antagonist molecules. In some embodiments, the first subpopulation constitutes about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, or about 90% of the population of FcRn antagonist molecules. In some embodiments, the first subpopulation constitutes 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% of the population of FcRn antagonist molecules. In some embodiments, the first subpopulation comprises 40% to 90%, 50% to 80%, or 55% to 70% of the population of FcRn antagonist molecules, or 56.9% to 68.3%, or 59.5% to 67.9% of the population of FcRn antagonist molecules.

[0125] In some embodiments, the second subpopulation comprises less than 3.0%, less than 2.5%, less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the second subpopulation comprises about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the second subpopulation comprises 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the second subpopulation comprises 0.5% to 3.0%, 1.0% to 2.5%, or 1.0% to 2.0% of the population of FcRn antagonist molecules. In some embodiments, the second subpopulation comprises 0.8% to 2.0% or 0.8% to 2.1% of the population of FcRn antagonist molecules.

[0126] In some embodiments, the third subpopulation constitutes less than 3.0%, less than 2.5%, less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the third subpopulation constitutes about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the third subpopulation constitutes 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the third subpopulation constitutes 0.5% to 3.0%, 1.0% to 2.5%, or 1.0% to 2.0% of the population of FcRn antagonist molecules. In some embodiments, the third subpopulation comprises 1.1% to 2.1% or 1.0% to 1.9% of the population of FcRn antagonist molecules.

[0127] In some embodiments, the fourth subpopulation constitutes less than 5%, less than 4%, less than 3%, less than 2%, or less than 1% of the population of FcRn antagonist molecules. In some embodiments, the fourth subpopulation constitutes about 5%, about 4%, about 3%, about 2%, or about 1% of the population of FcRn antagonist molecules. In some embodiments, the fourth subpopulation constitutes 5%, 4%, 3%, 2%, or 1% of the population of FcRn antagonist molecules. In some embodiments, the fourth subpopulation constitutes 1% to 5%, 2% to 4%, or 2% to 3% of the population of FcRn antagonist molecules. In some embodiments, the fourth subpopulation constitutes 2.1% to 3.2%, or 2.0% to 3.1% of the population of FcRn antagonist molecules.

[0128] In some embodiments, the fifth subpopulation constitutes less than 12%, less than 11%, less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, or less than 5% of the population of FcRn antagonist molecules. In some embodiments, the fifth subpopulation constitutes about 12%, about 11%, about 10%, about 9%, about 8%, about 7%, about 6%, or about 5% of the population of FcRn antagonist molecules. In some embodiments, the fifth subpopulation constitutes 12%, 11%, 10%, 9%, 8%, 7%, 6%, or 5% of the population of FcRn antagonist molecules. In some embodiments, the fifth subpopulation constitutes 5% to 12%, 6% to 10%, or 7% to 8% of the population of FcRn antagonist molecules. In some embodiments, the fifth subpopulation comprises 6.8% to 9.4% or 6.9% to 8.7% of the population of FcRn antagonist molecules.

[0129] In some embodiments, the sixth subpopulation constitutes less than 17%, less than 16%, less than 15%, less than 14%, less than 13%, less than 12%, less than 11%, less than 10%, less than 9%, less than 8%, less than 7%, or less than 6% of the population of FcRn antagonist molecules. In some embodiments, the sixth subpopulation constitutes about 17%, about 16%, about 15%, about 14%, about 13%, about 12%, about 11%, about 10%, about 9%, about 8%, about 7%, or about 6% of the population of FcRn antagonist molecules. In some embodiments, the sixth subpopulation constitutes 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, or 6% of the population of FcRn antagonist molecules. In some embodiments, the sixth subpopulation comprises 7% to 17%, 10% to 15%, or 11% to 12% of the population of FcRn antagonist molecules, hi some embodiments, the sixth subpopulation comprises 7.0% to 14.0%, or 10.0% to 14.4% of the population of FcRn antagonist molecules.

[0130] In some embodiments, the seventh subpopulation comprises less than 6.0%, less than 5.5%, less than 5.0%, less than 4.5%, less than 4.0%, less than 3.5%, less than 3.0%, less than 2.5%, less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules, hi some embodiments, the seventh subpopulation comprises about 6.0%, about 5.5%, about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the seventh subpopulation comprises 6.0%, 5.5%, 5.0%, 4.5%, 4.0%, 3.5%, 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the seventh subpopulation comprises 0.5% to 5.5%, 1.0% to 3.0%, or 1.5% to 2.5% of the population of FcRn antagonist molecules. In some embodiments, the seventh subpopulation comprises 1.5% to 5.5%, or 1.4% to 4.9% of the population of FcRn antagonist molecules.

[0131] In some embodiments, the eighth subpopulation comprises less than 7.5%, less than 7.0%, less than 6.5%, less than 6.0%, less than 5.5%, less than 5.0%, less than 4.5%, less than 4.0%, less than 3.5%, less than 3.0%, or less than 2.5% of the population of FcRn antagonist molecules, hi some embodiments, the eighth subpopulation comprises about 7.5%, about 7.0%, about 6.5%, about 6.0%, about 5.5%, about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, or about 2.5% of the population of FcRn antagonist molecules. In some embodiments, the eighth subpopulation comprises 7.5%, 7.0%, 6.5%, 6.0%, 5.5%, 5.0%, 4.5%, 4.0%, 3.5%, 3.0%, or 2.5% of the population of FcRn antagonist molecules. In some embodiments, the eighth subpopulation comprises 2.5% to 7.5%, 3.0% to 5.0%, or 3.5% to 4.5% of the population of FcRn antagonist molecules. In some embodiments, the eighth subpopulation comprises 2.9% to 7.4%, or 3.0% to 6.3% of the population of FcRn antagonist molecules.

[0132] In some embodiments, the ninth subpopulation constitutes less than 3.5%, less than 3.0%, less than 2.5%, less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the ninth subpopulation constitutes about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the ninth subpopulation constitutes 3.5%, 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the ninth subpopulation constitutes 0.5% to 3.5%, 1.5% to 2.0%, or 1.0% to 1.5% of the population of FcRn antagonist molecules. In some embodiments, the ninth subpopulation comprises 0.4% to 3.2% or 0.5% to 2.6% of the population of FcRn antagonist molecules.

[0133] In some embodiments, the tenth subpopulation comprises less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the tenth subpopulation comprises about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the tenth subpopulation comprises 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the tenth subpopulation comprises 0.5% to 2.0%, 0.5% to 1.5%, or 1.0% to 1.5% of the population of FcRn antagonist molecules.

[0134] In some embodiments, the 11th subpopulation constitutes less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the 11th subpopulation constitutes about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the 11th subpopulation constitutes 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the 11th subpopulation constitutes 0.5% to 2.0%, 0.5% to 1.5%, or 1.0% to 1.5% of the population of FcRn antagonist molecules.

[0135] In some embodiments, the population of FcRn antagonist molecules comprises one or more of the FcRn antagonists described herein. In some embodiments, the FcRn antagonist is any of those described in U.S. Patent Application No. 63 / 383,599, filed November 14, 2022, which is incorporated herein by reference in its entirety. In some embodiments, the FcRn antagonist is a population of FcRn antagonists described in U.S. Patent Application No. 63 / 383,599, filed November 14, 2022, which is incorporated herein by reference in its entirety.

[0136] In one embodiment, the FcRn antagonist is efgartigimod (CAS Registry Number 1821402-21-4). As used herein, the term "efgartigimod" is interchangeable with "efgartigimod alfa." In some embodiments, efgartigimod is efgartigimod alfa-fcab.

[0137] In one embodiment, the anti-FcRn antibody is rozanolixizumab (UCB7665), nipocalimab (M281), orilanolimab (ALXN1830 / SYNT001), or batoclimab (IMVT-1401 / RVT1401 / HBM9161).

[0138] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of an immunoglobulin to FcRn is nipocalimab, also known as M281. Nipocalimab is a full-length "Fc-dead" IgG1 monoclonal antibody. Nipocalimab is being administered as an intravenous infusion in Phase 2 clinical trials for the treatment of myasthenia gravis (MG), warm autoimmune hemolytic anemia (WAIHA), and hemolytic disease of the fetus and newborn (HDFN). Nipocalimab comprises the light chain (SEQ ID NO: 4) and heavy chain (SEQ ID NO: 5) sequences set forth in Table 3 below (the VL region of SEQ ID NO: 4 and the VH region of SEQ ID NO: 5 are underlined). [Table 3]

[0139] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of an immunoglobulin to FcRn is rozanolixizumab, also known as UCB7665. Rozanolixizumab is a full-length humanized IgG4 monoclonal antibody. Rozanolixizumab is being administered as a subcutaneous infusion in ongoing clinical trials for MG, immune thrombocytopenia (FTP), and chronic inflammatory demyelinating polyneuropathy (CIDP). Rozanolixizumab comprises the light chain (SEQ ID NO: 6) and heavy chain (SEQ ID NO: 7) sequences set forth in Table 4 below (the VL region of SEQ ID NO: 6 and the VH region of SEQ ID NO: 7 are underlined). [Table 4]

[0140] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of an immunoglobulin to FcRn is orilanolimab, also known as SYNT001. Orilanolimab is another full-length humanized IgG4 monoclonal antibody. Orilanolimab is being administered as an intravenous infusion in a Phase 2 clinical trial for the treatment of WAIHA. Orilanolimab comprises the light chain (SEQ ID NO: 8) and heavy chain (SEQ ID NO: 9) sequences set forth in Table 5 below (the VL region of SEQ ID NO: 8 and the VH region of SEQ ID NO: 9 are underlined). [Table 5]

[0141] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of an immunoglobulin to FcRn is batoclimab, also known as IMVT1401 / RVT1401 / HBM9161. Batoclimab is another full-length "Fc-dead" IgG1 monoclonal antibody. Batoclimab is being administered as a subcutaneous injection in ongoing Phase 2 clinical trials for the treatment of MG and Graves' ophthalmopathy. Batoclimab comprises the light chain (SEQ ID NO: 10) and heavy chain (SEQ ID NO: 11) sequences set forth in Table 6 below (the VL region of SEQ ID NO: 10 and the VH region of SEQ ID NO: 11 are underlined). [Table 6]

[0142] Pharmaceutical Compositions In one aspect, the present disclosure provides pharmaceutical compositions comprising an FcRn antagonist for use in methods for treating LN. In certain embodiments, these compositions comprise or consist of a variant Fc region, or an FcRn-binding fragment thereof, that specifically binds to FcRn, particularly human FcRn, with increased affinity and reduced pH dependency compared to a native Fc region. In other embodiments, the FcRn antagonist composition is an antibody or antigen-binding fragment thereof that specifically binds to FcRn via its antigen-binding domain and inhibits the binding of the Fc region of an immunoglobulin to FcRn. Generally, these FcRn antagonists inhibit the binding of Fc-containing agents (e.g., antibodies and immunoadhesins) to FcRn in vivo, which results in an increased degradation rate of the Fc-containing agent and, concomitantly, reduced serum levels of these agents.

[0143] In one embodiment, the FcRn antagonist is efgartigimod. Efgartigimod (ARGX-113) is a modified human immunoglobulin (Ig) gamma (IgG)1-derived Fc of the za allotype that binds to human FcRn with nanomolar affinity. Efgartigimod encompasses the IgG1 Fc region and has been engineered using ABDEG™ technology to increase its affinity for FcRn at both physiological and acidic pH. Efgartigimod's increased affinity for FcRn at both acidic and physiological pH results in blockage of FcRn-mediated recycling of IgG.

[0144] Due to its increased affinity for FcRn at both acidic and neutral pH, efgartigimod blocks the formation of FcRn / IgG complexes, leading to the degradation of endogenous IgG, including the autoantibodies that cause IgG-mediated autoimmune diseases. This blockade of FcRn by efgartigimod results in a rapid and significant reduction in autoantibody levels, providing the basis for a therapeutic strategy for the treatment of autoimmune indications in which IgG autoantibodies are expected to play a central role in disease pathology. Without wishing to be bound by theory, efgartigimod may act to prevent the onset or progression of LN by reducing circulating immune complexes and preventing their deposition in glomeruli. Indeed, efgartigimod has been shown to reduce circulating immune complexes (Example 1; Figure 1).

[0145] Efgartigimod is in development for both intravenous (IV) and subcutaneous (SC) routes of administration.

[0146] For IV administration, in certain embodiments, efgartigimod may be administered in a formulation comprising sodium phosphate, sodium chloride, L-arginine hydrochloride, and polysorbate 80. In certain embodiments, efgartigimod may be administered in a formulation comprising about 25 mM sodium phosphate, about 100 mM sodium chloride, and about 150 mM L-arginine hydrochloride (pH 6.7), and about 0.02% (w / v) polysorbate 80. In certain embodiments, efgartigimod may be administered in a formulation comprising 25 mM sodium phosphate, 100 mM sodium chloride, and 150 mM L-arginine hydrochloride (pH 6.7), and 0.02% (w / v) polysorbate 80. In certain embodiments, efgartigimod can be administered via intravenous infusion in a total volume of about 250 mL over a period of about 2 hours in a formulation comprising about 25 mM sodium phosphate, about 100 mM sodium chloride, and about 150 mM L-arginine hydrochloride (pH 6.7), and about 0.02% (w / v) polysorbate 80. In certain embodiments, efgartigimod can be administered via intravenous infusion in a total volume of 250 mL over a period of about 2 hours in a formulation comprising 25 mM sodium phosphate, 100 mM sodium chloride, and 150 mM L-arginine hydrochloride (pH 6.7), and 0.02% (w / v) polysorbate 80. See, e.g., WO2019 / 110823A1, which is incorporated herein by reference in its entirety.

[0147] In certain embodiments, efgartigimod may be administered over a period of about 1 hour in a formulation comprising an aqueous solution having a pH of about 6.7, the aqueous solution comprising about 25 mM sodium phosphate, about 100 mM sodium chloride, and about 150 mM L-arginine hydrochloride, and about 0.02% (w / v) polysorbate 80, diluted to a total volume of about 125 mL for intravenous infusion. In certain embodiments, efgartigimod may be administered over a period of about 1 hour in a formulation comprising an aqueous solution having a pH of about 6.7, the aqueous solution comprising 25 mM sodium phosphate, 100 mM sodium chloride, and 150 mM L-arginine hydrochloride, and 0.02% (w / v) polysorbate 80, diluted to a total volume of 125 mL for intravenous infusion.

[0148] In certain embodiments, efgartigimod may be administered in a formulation comprising an aqueous solution having a pH of about 6.7, the aqueous solution comprising about 4 mM sodium phosphate, about 146 mM sodium chloride, about 24 mM L-arginine, and about 0.0032% (w / v) polysorbate 80. The formulation is administered via intravenous infusion in a total volume of about 125 mL over a period of about 1 hour. In certain embodiments, efgartigimod may be administered in a formulation comprising an aqueous solution having a pH of about 6.7, the aqueous solution comprising 4 mM sodium phosphate, 146 mM sodium chloride, 24 mM L-arginine, and 0.0032% (w / v) polysorbate 80. The formulation is administered via intravenous infusion in a total volume of 125 mL over a period of 1 hour.

[0149] In certain embodiments, efgartigimod is administered via IV infusion and is provided in a sterile, clear, concentrated solution at a concentration of about 20 mg / mL. In certain embodiments, efgartigimod is administered via IV infusion and is provided in a sterile, clear, concentrated solution at a concentration of 20 mg / mL.

[0150] In certain embodiments, efgartigimod is administered via IV infusion and is provided in a vial (e.g., a single-dose vial). In certain embodiments, a vial of efgartigimod contains about 400 mg of efgartigimod at a concentration of about 20 mg / mL. In certain embodiments, a vial of efgartigimod contains 400 mg of efgartigimod at a concentration of 20 mg / mL. In certain embodiments, each mL of solution in a vial of efgartigimod contains about 31.6 mg of L-arginine hydrochloride, about 0.2 mg of polysorbate 80, about 5.8 mg of sodium chloride, about 2.4 mg of sodium phosphate dibasic anhydrous, about 1.1 mg of sodium phosphate monobasic monohydrate, and water for injection, USP, at a pH of about 6.7. In certain embodiments, each mL of solution in a vial of efgartigimod contains 31.6 mg of L-arginine hydrochloride, 0.2 mg of polysorbate 80, 5.8 mg of sodium chloride, 2.4 mg of sodium phosphate dibasic anhydrous, 1.1 mg of sodium phosphate monobasic monohydrate, and water for injection, USP, at a pH of about 6.7.

[0151] In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered as an IV infusion at a dose of about 10 mg / kg. In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered as an IV infusion at a dose of about 10 mg / kg over about 1 hour. In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered as an IV infusion at a dose of about 10 mg / kg over about 1 hour once a week. In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered as an IV infusion at a dose of about 10 mg / kg over about 1 hour once a week for about 4 weeks. In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered as an IV infusion at a dose of 10 mg / kg. In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered at a dose of 10 mg / kg as an IV infusion over one hour. In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered at a dose of 10 mg / kg as an IV infusion over one hour once a week. In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered at a dose of 10 mg / kg as an IV infusion over one hour once a week for four weeks. In certain embodiments, for patients weighing 120 kg or more, efgartigimod is administered at a dose of about 1200 mg per IV infusion. In certain embodiments, for patients weighing 120 kg or more, efgartigimod is administered at a dose of 1200 mg per IV infusion.

[0152] For SC administration, in certain embodiments, efgartigimod may be administered alone. Alternatively, for SC administration, in certain embodiments, efgartigimod may be co-formulated with hyaluronidase, such as, in particular, rHuPH20, and administered. Co-formulated materials may allow for larger SC administration volumes.

[0153] In some embodiments, efgartigimod may be administered in a formulation comprising an aqueous solution comprising about 20 mM L-histidine, about 100 mM sodium chloride, about 60 mM sucrose, about 10 mM L-methionine, and about 0.04% (w / v) polysorbate 20, wherein the composition has a pH of about 6.0. In some embodiments, the formulation comprises about 180 mg / ml efgartigimod. In some embodiments, efgartigimod may be administered in a formulation comprising an aqueous solution comprising 20 mM L-histidine, 100 mM sodium chloride, 60 mM sucrose, 10 mM L-methionine, and 0.04% (w / v) polysorbate 20, wherein the composition has a pH of 6.0. In some embodiments, the formulation comprises 180 mg / ml efgartigimod.

[0154] In some embodiments, efgartigimod may be administered in a formulation comprising an aqueous solution comprising about 20 mM L-histidine, about 50 mM L-arginine, about 100 mM sodium chloride, about 60 mM sucrose, about 10 mM L-methionine, and about 0.04% (w / v) polysorbate 80, wherein the composition has a pH of about 6.0. In some embodiments, the formulation comprises about 200 mg / ml efgartigimod. In some embodiments, efgartigimod may be administered in a formulation comprising an aqueous solution comprising 20 mM L-histidine, 50 mM L-arginine, 100 mM sodium chloride, 60 mM sucrose, 10 mM L-methionine, and 0.04% (w / v) polysorbate 80, wherein the composition has a pH of 6.0. In some embodiments, the formulation contains 200 mg / ml efgartigimod. rHuPH20 is the active ingredient in Halozyme's commercial product, HYLENEX® Recombinant (Hyaluronidase Human Injection), designated HYLENEX®, which was approved by the FDA for commercial use in the United States in December 2005. HYLENEX® is a tissue permeability modifier indicated as an adjuvant in SC fluid administration to achieve hydration, to increase the dispersion and absorption of other injected medications, and in SC urography to improve resorption of radiopaque agents.

[0155] rHuPH20 is a recombinant enzyme, human hyaluronidase, produced by genetically engineered Chinese hamster ovary (CHO) cells containing a deoxyribonucleic acid plasmid encoding a soluble fragment of human hyaluronidase (occipital protein 20 [PH20]).

[0156] HZ202 rHuPH20 DS is currently registered in HYLENEX® and other biologic products co-formulated with rHuPH20 DS. Accordingly, in certain embodiments, HZ202 rHuPH20 DS is used in an efgartigimod / rHuPH20 co-formulated product for SC administration (i.e., efgartigimod PH20 SC).

[0157] Soluble hyaluronidases are provided in the co-formulations, combinations, uses, and methods herein. Soluble hyaluronidases include any that are secreted from cells upon expression and exist in a soluble form. Such soluble hyaluronidases include, but are not limited to, bacterial soluble hyaluronidases, non-human soluble hyaluronidases, such as bovine PH20 and ovine PH20, human soluble PH20, and variants thereof. Generally, soluble forms of PH20 are produced using protein expression systems that facilitate correct N-glycosylation to ensure that the polypeptide retains activity, as glycosylation is important for the catalytic activity and stability of hyaluronidase. Such cells include, for example, Chinese hamster ovary (CHO) cells (e.g., DG44 CHO cells).

[0158] rHuPH20 refers to a composition produced upon expression in cells, e.g., CHO cells, generally of a nucleic acid encoding residues 36-482 of SEQ ID NO:32 linked to a native or heterologous signal sequence (residues 1-35 of SEQ ID NO:32). rHuPH20 is produced by expression of a nucleic acid molecule, e.g., encoding amino acids 1-482 (set forth in SEQ ID NO:32), in mammalian cells. Translational processing removes the 35-amino acid signal sequence. When produced in culture medium, there is heterogeneity at the C-terminus, such that the product designated rHuPH20 contains a mixture of species that may include any one or more of polypeptides 36-480, 36-481, and 36-482 of SEQ ID NO:32, as well as several shorter polypeptides in varying abundance. Typically, rHuPH20 is produced in cells, e.g., CHO cells (e.g., DG44 CHO cells), that facilitate correct N-glycosylation to retain activity. In some embodiments, one of the most abundant species is a 446 amino acid polypeptide corresponding to residues 36-481 of SEQ ID NO: 32. Also included are polypeptides that are soluble or secreted upon expression in mammalian cells and that have at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity to residues 36-482 of SEQ ID NO: 32.

[0159] In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of about 20 mg to about 20,000 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of about 200 mg to about 20,000 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of about 300 mg to about 6000 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of about 750 mg to about 3000 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of about 1000 mg to about 2500 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of about 1000 mg to about 2000 mg.

[0160] In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of 20 mg to about 20,000 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of 200 mg to about 20,000 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of 300 mg to about 6000 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of 750 mg to about 3000 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of 1000 mg to about 2500 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of 1000 mg to about 2000 mg.

[0161] In some embodiments, the pharmaceutical formulation comprises about 1000 mg or about 2000 mg of the FcRn antagonist. In some embodiments, the pharmaceutical formulation comprises 1000 mg or 2000 mg of the FcRn antagonist. In some embodiments, the FcRn antagonist is efgartigimod.

[0162] In some embodiments, the pharmaceutical formulation comprises efgartigimod in an amount of about 800 mg to about 1200 mg. In some embodiments, the pharmaceutical formulation comprises about 1000 mg of efgartigimod. In some embodiments, the pharmaceutical formulation comprises 1000 mg of efgartigimod.

[0163] In some embodiments, the pharmaceutical formulation comprises about 10 mg / mL to about 200 mg / mL of efgartigimod. In some embodiments, the pharmaceutical formulation comprises 10 mg / mL to 200 mg / mL of efgartigimod.

[0164] In some embodiments, the pharmaceutical formulation comprises about 20 mg / mL of efgartigimod. In some embodiments, the pharmaceutical formulation comprises 20 mg / mL of efgartigimod.

[0165] In some embodiments, the pharmaceutical formulation comprises about 180 mg / ml of efgartigimod. In some embodiments, the pharmaceutical formulation comprises 180 mg / ml of efgartigimod.

[0166] In some embodiments, the pharmaceutical formulation further comprises a hyaluronidase. In some embodiments, the hyaluronidase is recombinant human hyaluronidase PH20 (rHuPH20).

[0167] Hyaluronidase can be present in the pharmaceutical formulation in any suitable amount. In one embodiment, the amount of hyaluronidase enzyme is about 1000 U / ml to about 3000 U / ml. In one embodiment, the amount of hyaluronidase enzyme is about 1000 U / mL, about 1500 U / mL, about 2000 U / mL, about 2500 U / mL, or about 3000 U / mL. In one embodiment, the amount of hyaluronidase enzyme is 2000 U / mL.

[0168] In some embodiments, rHuPH20 is present in the pharmaceutical formulation in an amount of about 11,000 U. In some embodiments, rHuPH20 is present in the pharmaceutical formulation in an amount of 11,000 U.

[0169] In some embodiments, the pharmaceutical formulation comprises at least about 5 U to at least about 100,000 U of an endoglycosidase hydrolase enzyme. In some aspects, the pharmaceutical formulation comprises at least about 5 U, at least about 10 U, at least about 20 U, at least about 30 U, at least about 40 U, ​​at least about 50 U, at least about 75 U, at least about 100 U, at least about 200 U, at least about 300 U, at least about 400 U, at least about 500 U, at least about 750 U, at least about 1000 U, at least about 2000 U, at least about 3000 U, at least about 4000 U, at least about 5000 U, at least about 6000 U, at least about 7000 U, at least about 8000 U, at least about 9000 U, at least about 10,000 U, at least about 20,000 U, at least about 30,000 U, at least about 40,000 U, at least about 50,000 U, at least about 60,000 U, at least about 70,000 U, at least about 80,000 U, at least about 90,000 U, or at least about 100,000 U of endoglycosidase hydrolase enzyme.

[0170] In some embodiments, the pharmaceutical formulation comprises about 20,000 U of endoglycosidase hydrolase enzyme. In some embodiments, the pharmaceutical formulation comprises at least about 500 U / mL to at least about 5000 U / mL of endoglycosidase hydrolase enzyme. In some embodiments, the pharmaceutical formulation comprises at least about 1500 U / mL, at least about 1600 U / mL, at least about 1700 U / mL, at least about 1800 U / mL, at least about 1900 U / mL, at least about 2000 U / mL, at least about 2100 U / mL, at least about 2200 U / mL, at least about 2300 U / mL, at least about 2400 μM, at least about 2500 μM, at least about 3000 μM, at least about 3500 μM, at least about 4000 μM, at least about 4500 U / mL, or at least about 5000 U / mL of endoglycosidase hydrolase enzyme. In some embodiments, the pharmaceutical formulation comprises about 2000 U / mL of an endoglycosidase hydrolase enzyme.

[0171] In some embodiments, the endoglycosidase hydrolase enzyme cleaves hyaluronic acid in hexosaminide β(1-4) or (1-3) linkages. In some embodiments, the endoglycosidase hydrolase enzyme comprises the catalytic domain of hyaluronidase PH-20 (HuPH20), HYAL1, HYAL2, HYAL3, HYAL4, or HYALPS1. In some embodiments, the endoglycosidase hydrolase enzyme comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% sequence identity to amino acids 36-490 of SEQ ID NO: 32. In some embodiments, the endoglycosidase hydrolase enzyme comprises a hyaluronidase. In some embodiments, the endoglycosidase hydrolase enzyme comprises a hyaluronidase selected from the group consisting of HuPH20, HYAL1, HYAL2, HYAL3, HYAL4, any variant and any isoform thereof, hi some embodiments, the endoglycosidase hydrolase enzyme comprises rHuPH20 or a fragment thereof.

[0172] In some embodiments, the endoglycosidase hydrolase enzyme comprises a modified hyaluronidase that comprises one or more amino acid substitutions relative to a wild-type hyaluronidase selected from the group consisting of HuPH20, HYAL1, HYAL2, HYAL3, HYAL4, HYALPS1, or a fragment thereof. In some embodiments, the endoglycosidase hydrolase enzyme comprises a modified hyaluronidase that comprises one or more amino acid substitutions in the alpha helix region relative to a wild-type hyaluronidase selected from the group consisting of HuPH20, HYAL1, HYAL2, HYAL3, HYAL4, HYALPS1, or a fragment thereof. In some embodiments, the endoglycosidase hydrolase enzyme comprises a modified hyaluronidase that comprises one or more amino acid substitutions in the linker region relative to a wild-type hyaluronidase selected from the group consisting of HuPH20, HYAL1, HYAL2, HYAL3, HYAL4, HYALPS1, or a fragment thereof. In some embodiments, the endoglycosidase hydrolase enzyme comprises a modified hyaluronidase in which one or more N-terminal and / or C-terminal amino acids are deleted relative to a wild-type hyaluronidase selected from the group consisting of HuPH20, HYAL1, HYAL2, HYAL3, HYAL4, HYALPS1, or a fragment thereof. In some embodiments, the endoglycosidase hydrolase enzyme comprises a modified rHuPH20 in which: i. one or more amino acid substitutions in the alpha-helical region, the linker region, or both the alpha-helical region and the linker region relative to wild-type rHuPH20; ii. a deletion of one or more N-terminal amino acids, one or more C-terminal amino acids, or one or more N-terminal and one or more C-terminal amino acids relative to wild-type rHuPH20; or iii. both (i) and (ii).

[0173] As used herein, "hyaluronidase" refers to an enzyme capable of catalyzing the cleavage of hyaluronan. Hyaluronan is a repeating polymer of N-acetylglucosamine and glucuronic acid that resides in the subcutaneous space, contributes to the soluble gel-like component of the skin's extracellular matrix, and is restored by rapid turnover (resynthesis). In some embodiments, the hyaluronidase comprises rHuPH20, a glycosylated 447 amino acid single-chain polypeptide that depolymerizes hyaluronan in the subcutaneous space locally at the site of injection in the skin. Depolymerization of hyaluronan by hyaluronidase is achieved by hydrolysis of the polysaccharide polymer. Depolymerization of hyaluronan results in a transient reduction in the viscosity of the gel-like phase of the extracellular matrix and increased hydraulic conductance, facilitating the dispersion and absorption of co-administered therapeutic agents. Thus, hyaluronidases, such as rHuPH20, can improve the speed and ease of subcutaneous delivery of injectable biologics and drugs by acting as penetration enhancers. In certain embodiments, the hyaluronidase comprises ENHANZE™.

[0174] In any of the above embodiments, the pharmaceutical formulation may be in unit dosage form.

[0175] In one embodiment, the unit dosage form comprises the FcRn antagonist as a dry formulation for dissolution, such as a lyophilized powder, freeze-dried powder, or water-free concentrate. In one embodiment, the dry formulation is contained in a hermetically sealed container, such as a vial, ampoule, or sachet.

[0176] In one embodiment, the unit dosage form comprises an FcRn antagonist as a liquid formulation, e.g., an injection or infusion solution, hi one embodiment, the liquid formulation is contained in a sealed container such as a vial, a sachet, a pre-filled syringe, a pre-filled auto-injector, or a cartridge for a reusable syringe or applicator.

[0177] In one embodiment, the unit dosage per vial may contain 0.5 ml, 1 ml, 2 ml, 3 ml, 4 ml, 5 ml, 6 ml, 7 ml, 8 ml, 9 ml, 10 ml, 15 ml, or 20 ml of FcRn antagonist in the range of about 500 to about 2500 mg or about 1000 to about 2000 mg. In one embodiment, these preparations can be adjusted to the desired concentration by adding a sterile diluent to each vial.

[0178] The formulations disclosed herein include bulk drug compositions useful for manufacturing pharmaceutical compositions (e.g., compositions suitable for administration to a subject or patient) that can be used to prepare unit dosage forms. In one embodiment, the compositions of the invention are pharmaceutical compositions. Such compositions comprise a prophylactically or therapeutically effective amount of one or more prophylactic or therapeutic agents (e.g., an FcRn antagonist of the invention or other prophylactic or therapeutic agent) and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition is formulated to be suitable for subcutaneous administration to a subject.

[0179] method In one aspect, a method for treating LN using an FcRn antagonist is provided. In a specific embodiment, the FcRn antagonist is efgartigimod. An important goal and feature of the methods disclosed herein is the prevention of progression to end-stage renal disease (ESRD) in patients with LN. Other goals and features of the methods disclosed herein include, but are not limited to, patient survival, long-term maintenance of kidney function, prevention of disease flares, prevention of organ damage, management of comorbidities, and improvement in disease-related quality of life. Effective treatment of LN using an FcRn antagonist may include at least one of the following elements: an early reduction in UPCR, an improvement in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K score, and / or an improvement in estimated glomerular filtration rate (eGFR). In some embodiments, UPCR is calculated by dividing the protein level (mg / dL) by the creatinine level (mg / dL) in a spot urine test. The SLEDAI-2K is a questionnaire that determines disease activity in lupus. In some embodiments, a subject treated by the methods provided herein experiences a complete renal response (CRR). In some embodiments, a subject treated by the methods provided herein experiences a modified complete renal response (mCRR). In some embodiments, a subject treated by the methods provided herein experiences a partial renal response (PRR). In some embodiments, a subject treated by the methods provided herein experiences a reduction in circulating immune complexes. In some embodiments, the circulating immune complexes are selected from the group consisting of C3, C4, CH50, and C1q-bound circulating immune complexes.

[0180] As used herein, a complete renal response (CRR) in a subject is defined as 60 mL / min / 1.73 m 2 This is defined as an eGFR of ≥ 0.5 mg / mg or no confirmed decrease of > 20% from the baseline eGFR value and a UPCR of ≤ 0.5 mg / mg.

[0181] As used herein, a modified complete renal response (mCRR) in a subject is defined as 90 mL / min / 1.73 m2 This is defined as an eGFR of ≥ 0.5 mg / mg or no confirmed decrease of > 10% from the baseline eGFR value, and a UPCR of ≤ 0.5 mg / mg.

[0182] As used herein, a partial renal response (PRR) in a subject is defined as 60 mL / min / 1.73 m 2 A post-dose UPCR is defined as a decrease in eGFR of ≥ 1.0 mg / mg if baseline UPCR is ≤ 3.0 mg / mg, or a post-dose UPCR of < 3.0 mg / mg if baseline UPCR is > 3.0 mg / mg.

[0183] In some embodiments, LN may be characterized by a positive antinuclear antibody (ANA) test result in the subject (e.g., an ANA titer of 1:80 or greater). In some embodiments, LN may be characterized by elevated anti-dsDNA (e.g., 30 IU / mL or greater) or low complement levels (e.g., C3 less than 0.9 g / L or C4 less than 0.1 g / L) in the subject. In some embodiments, LN may be characterized by a UPCR of 1.0 mg / mL or greater in the subject. In some embodiments, LN may be characterized by a blood glucose level of 60 mL / min / 1.73 mHg in the subject. 2 In some embodiments, LN may be characterized by an eGFR of 6 g / L or greater in a subject. In some embodiments, LN may be characterized by a serum total IgG of 4 g / L or greater in a subject.

[0184] In some embodiments, the subject has LN class III or class IV. In some embodiments, the subject does not have LN class III(C), IV-S(C), and IV-G(C). In some embodiments, the subject has LN class I. In some embodiments, the subject has LN class II. In some embodiments, the subject has LN class III. In some embodiments, the subject has LN class IV. In some embodiments, the subject has LN class V. In some embodiments, the subject has LN class VI. In some embodiments, the subject has LN class III and class V. In some embodiments, the subject has LN class IV and class V.

[0185] In some embodiments, the FcRn antagonist is administered at a fixed dose of about 20 mg to about 20,000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 200 mg to about 20,000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 300 mg to about 6000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 750 mg to about 3000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 1000 mg to about 2500 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 1000 mg to about 2000 mg. In some embodiments, the FcRn antagonist is efgartigimod.

[0186] In some embodiments, the FcRn antagonist is administered at a fixed dose of 20 mg to 20,000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 200 mg to 20,000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 300 mg to 6000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 750 mg to 3000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 1000 mg to 2500 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 1000 mg to 2000 mg. In some embodiments, the FcRn antagonist is efgartigimod.

[0187] In some embodiments, the FcRn antagonist is administered at a fixed dose of about 20 mg, about 50 mg, about 100 mg, about 200 mg, about 250 mg, about 300 mg, about 500 mg, about 750 mg, about 1000 mg, about 1500 mg, about 2000 mg, about 2500 mg, about 3000 mg, about 4000 mg, about 5000 mg, about 6000 mg, about 7000 mg, about 8000 mg, about 9000 mg, about 10,000 mg, about 11,000 mg, about 12,000 mg, about 13,000 mg, about 14,000 mg, about 15,000 mg, about 16,000 mg, about 17,000 mg, about 18,000 mg, about 19,000 mg, or about 20,000 mg. In some embodiments, the FcRn antagonist is efgartigimod.

[0188] In some embodiments, the FcRn antagonist is administered at a fixed dose of 20 mg, 50 mg, 100 mg, 200 mg, 250 mg, 300 mg, 500 mg, 750 mg, 1000 mg, 1500 mg, 2000 mg, 2500 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 7000 mg, 8000 mg, 9000 mg, 10,000 mg, 11,000 mg, 12,000 mg, 13,000 mg, 14,000 mg, 15,000 mg, 16,000 mg, 17,000 mg, 18,000 mg, 19,000 mg, or 20,000 mg. In some embodiments, the FcRn antagonist is efgartigimod.

[0189] In some embodiments, the FcRn antagonist is administered at a dose of about 0.2 mg / kg to about 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 2 mg / kg to about 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 2 mg / kg to about 120 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 3 mg / kg to about 60 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 10 mg / kg to about 25 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod.

[0190] In some embodiments, the FcRn antagonist is administered at a dose of 0.2 mg / kg to 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 2 mg / kg to about 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of 2 mg / kg to 120 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of 3 mg / kg to 60 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of 10 mg / kg to 25 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod.

[0191] In some embodiments, the FcRn antagonist is administered at a dose of about 0.2 mg / kg, about 0.5 mg / kg, about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 12.5 mg / kg, about 15 mg / kg, about 17.5 mg / kg, about 20 mg / kg, about 25 mg / kg, about 30 mg / kg, about 35 mg / kg, about 40 mg / kg, about 45 mg / kg, In some embodiments, the FcRn antagonist is efgartigimod.

[0192] In some embodiments, the FcRn antagonist is administered at a dose of 0.2 mg / kg, 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, In some embodiments, the FcRn antagonist is efgartigimod.

[0193] In some embodiments, the FcRn antagonist is administered intravenously. In some embodiments, the FcRn antagonist is administered intravenously once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0194] In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 0.2 mg / kg to about 200 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 2 mg / kg to about 200 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 2 mg / kg to about 120 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 3 mg / kg to about 60 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 10 mg / kg to about 25 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0195] In some embodiments, the FcRn antagonist is administered at a dose of about 0.2 mg / kg, about 0.5 mg / kg, about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 12.5 mg / kg, about 15 mg / kg, about 17.5 mg / kg, about 20 mg / kg, about 25 mg / kg, about 30 mg / kg, about 35 mg / kg, about 40 mg / kg, about 45 mg / kg, about 50 mg / kg, about In some embodiments, the FcRn antagonist is efgartigimod, administered intravenously once a week or once every two weeks at a dose of about 55 mg / kg, about 60 mg / kg, about 65 mg / kg, about 70 mg / kg, about 75 mg / kg, about 80 mg / kg, about 85 mg / kg, about 90 mg / kg, about 95 mg / kg, about 100 mg / kg, about 110 mg / kg, about 120 mg / kg, about 130 mg / kg, about 140 mg / kg, about 150 mg / kg, about 160 mg / kg, about 170 mg / kg, about 180 mg / kg, about 190 mg / kg, or about 200 mg / kg.

[0196] In some embodiments, the FcRn antagonist is administered at 0.2 mg / kg, 0.5 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 ... In some embodiments, the FcRn antagonist is efgartigimod, administered intravenously once a week or once every two weeks at a dose of 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, 100 mg / kg, 110 mg / kg, 120 mg / kg, 130 mg / kg, 140 mg / kg, 150 mg / kg, 160 mg / kg, 170 mg / kg, 180 mg / kg, 190 mg / kg, or 200 mg / kg.

[0197] In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 10 mg / kg to about 30 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 10 mg / kg to about 25 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 10 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 15 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 20 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 25 mg / kg, once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 30 mg / kg, once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 10 mg / kg to 30 mg / kg, once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of about 10 mg / kg to 25 mg / kg, once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 10 mg / kg, once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 15 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 20 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 25 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered intravenously at a dose of 30 mg / kg once a week or once every two weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0198] In some embodiments, the FcRn antagonist is administered intravenously once every two weeks for 52 weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0199] In some embodiments, the FcRn antagonist is administered subcutaneously. In some embodiments, the FcRn antagonist is administered subcutaneously once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0200] In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 20 mg to about 20,000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 100 mg to about 10,000 mg once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 750 mg to 3,000 mg once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg to 2000 mg once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0201] In some embodiments, the FcRn antagonist is administered in an amount of about 20 mg, about 50 mg, about 100 mg, about 250 mg, about 500 mg, about 750 mg, about 1000 mg, about 1500 mg, about 2000 mg, about 3000 mg, about 4000 mg, about 5000 mg, about 6000 mg, about 7000 mg, about 8000 mg, about 9000 mg, about 10,000 mg, about 11,000 mg, or about 12,000 mg. In some embodiments, the FcRn antagonist is efgartigimod, administered subcutaneously at a fixed dose of about 0 mg, about 12,000 mg, about 13,000 mg, about 14,000 mg, about 15,000 mg, about 16,000 mg, about 17,000 mg, about 18,000 mg, about 19,000 mg, or about 20,000 mg once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks.

[0202] In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 20 mg, 50 mg, 100 mg, 250 mg, 500 mg, 750 mg, 1000 mg, 1500 mg, 2000 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 7000 mg, 8000 mg, 9000 mg, 10,000 mg, 11,000 mg, 12,000 mg, 13,000 mg, 14,000 mg, 15,000 mg, 16,000 mg, 17,000 mg, 18,000 mg, 19,000 mg, or 20,000 mg once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg or 2000 mg once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0203] In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 750 mg to about 3000 mg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 1000 mg to about 2000 mg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 1000 mg or about 2000 mg once a week or once every two weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0204] In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 750 mg to 3000 mg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 750 mg to 3000 mg once a week. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 750 mg to 3000 mg once every two weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 750 mg to 3000 mg once every three weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 750 mg to 3000 mg once a month. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg to 2000 mg once a week or once every two weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg or 2000 mg once a week or once every two weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0205] In some embodiments, the FcRn antagonist is initially administered subcutaneously at a fixed dose of about 1000 mg twice on the same day. In some embodiments, the FcRn antagonist is initially administered subcutaneously at a fixed dose of 1000 mg twice on the same day. In some embodiments, the FcRn antagonist is efgartigimod.

[0206] In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of about 750 mg to about 1750 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of about 800 mg to about 1200 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of about 750 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of about 800 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of about 1000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of about 1200 mg. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 1250 mg once a week. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 1500 mg once a week. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 1750 mg once a week. In some embodiments, the FcRn antagonist is efgartigimod.

[0207] In some embodiments, the FcRn antagonist is administered subcutaneously once per week at a fixed dose of 750 mg to 1750 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once per week at a fixed dose of 800 mg to 1200 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once per week at a fixed dose of 750 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once per week at a fixed dose of 800 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once per week at a fixed dose of 1000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once per week at a fixed dose of 1200 mg. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of about 1250 mg once a week. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1500 mg once a week. In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose of 1750 mg once a week. In some embodiments, the FcRn antagonist is efgartigimod.

[0208] In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of about 10 mg / kg to about 25 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of about 10 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of about 15 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of about 20 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of about 25 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod.

[0209] In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of 10 mg / kg to 25 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of 10 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of 15 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of 20 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a dose of 25 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod.

[0210] In some embodiments, the FcRn antagonist is initially administered intravenously, followed by subcutaneous administration. In some embodiments, the FcRn antagonist is initially administered intravenously, followed by subcutaneous administration at a fixed dose of 100 mg to 10,000 mg once per week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every month, or once every 6 weeks. In some embodiments, the FcRn antagonist is initially administered intravenously, followed by subcutaneous administration at a fixed dose of 1000 mg or 2000 mg once per week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once every month, or once every 6 weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0211] In some embodiments, one or more doses of the FcRn antagonist are administered intravenously, followed by subcutaneous administration of subsequent doses of the FcRn antagonist. In some embodiments, one or more doses of the FcRn antagonist are administered intravenously, followed by subcutaneous administration of subsequent doses of the FcRn antagonist at a fixed dose of 100 mg to 10,000 mg once per week, once every two weeks, once every three weeks, once every four weeks, once per month, or once per six weeks. In some embodiments, one or more doses of the FcRn antagonist are administered intravenously, followed by subcutaneous administration of subsequent doses of the FcRn antagonist at a fixed dose of 1000 mg or 2000 mg once per week, once every two weeks, once every three weeks, once every four weeks, once per month, or once per six weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0212] In some embodiments, the FcRn antagonist is administered for 6, 12, 24, 39, or 52 weeks or less. In some embodiments, the FcRn antagonist is administered for 24 weeks or less. In some embodiments, the FcRn antagonist is administered for 52 weeks or less. In some embodiments, the FcRn antagonist is administered for at least 6, 12, 24, 39, or 52 weeks. In some embodiments, the FcRn antagonist is administered for at least 24 weeks. In some embodiments, the FcRn antagonist is administered for at least 52 weeks.

[0213] In some embodiments, the FcRn antagonist is rozanolixizumab. In some embodiments, rozanolixizumab is administered subcutaneously or intravenously. In some embodiments, rozanolixizumab is administered at a dose of about 0.2 mg / kg to about 200 mg / kg, or at a fixed dose of about 20 mg to about 20,000 mg, once weekly, once every 2 weeks, once every 3 weeks, once every 4 weeks, once a month, or once every 6 weeks.

[0214] In some embodiments, rozanolixizumab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, or about 25 mg / kg. g / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38mg / kg, about 39mg / kg, about 40mg / kg, about 41mg / kg, about 42mg / kg, about 43mg / kg, about 44mg / kg, about 45mg / kg, about 46mg / kg, about 47mg / kg, about 48mg / kg, about 49mg / kg, about 50mg / kg kg, approximately 51mg / kg, approximately 52mg / kg, approximately 53mg / kg, approximately 54mg / kg, approximately 55mg / kg, approximately 56mg / kg, approximately 57mg / kg, approximately 58mg / kg, approximately 59mg / kg, approximately 60mg / kg, approximately 61mg / kg, approximately 62mg / kg, approximately 63mg / k g, about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg , about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once a week.

[0215] In some embodiments, rozanolixizumab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, or about 25 mg / kg. g / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, approximately 38mg / kg, approximately 39mg / kg, approximately 40mg / kg, approximately 41mg / kg, approximately 42mg / kg, approximately 43mg / kg, approximately 44mg / kg, approximately 45mg / kg, approximately 46mg / kg, approximately 47mg / kg, approximately 48mg / kg, approximately 49mg / kg, approximately 50mg / k g, about 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, about and administered once every two weeks at a dose of 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0216] In some embodiments, rozanolixizumab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, or about 25 mg / kg. g / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, approximately 38mg / kg, approximately 39mg / kg, approximately 40mg / kg, approximately 41mg / kg, approximately 42mg / kg, approximately 43mg / kg, approximately 44mg / kg, approximately 45mg / kg, approximately 46mg / kg, approximately 47mg / kg, approximately 48mg / kg, approximately 49mg / kg, approximately 50mg / k g, about 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, about and administered once every three weeks at a dose of 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0217] In some embodiments, rozanolixizumab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, or about 25 mg / kg. g / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, approximately 38mg / kg, approximately 39mg / kg, approximately 40mg / kg, approximately 41mg / kg, approximately 42mg / kg, approximately 43mg / kg, approximately 44mg / kg, approximately 45mg / kg, approximately 46mg / kg, approximately 47mg / kg, approximately 48mg / kg, approximately 49mg / kg, approximately 50mg / k g, about 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, about and administered once every four weeks at a dose of 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0218] In some embodiments, rozanolixizumab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, or about 25 mg / kg. g / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38mg / kg, about 39mg / kg, about 40mg / kg, about 41mg / kg, about 42mg / kg, about 43mg / kg, about 44mg / kg, about 45mg / kg, about 46mg / kg, about 47mg / kg, about 48mg / kg, about 49mg / kg, about 50mg / kg kg, approximately 51mg / kg, approximately 52mg / kg, approximately 53mg / kg, approximately 54mg / kg, approximately 55mg / kg, approximately 56mg / kg, approximately 57mg / kg, approximately 58mg / kg, approximately 59mg / kg, approximately 60mg / kg, approximately 61mg / kg, approximately 62mg / kg, approximately 63mg / k g, about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg , about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once a month.

[0219] In some embodiments, the FcRn antagonist is nipocalimab. In some embodiments, nipocalimab is administered subcutaneously or intravenously. In some embodiments, nipocalimab is administered at a dose of about 0.2 mg / kg to about 200 mg / kg, or at a fixed dose of about 20 mg to about 20,000 mg, once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks.

[0220] In some embodiments, nipocalimab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / k g, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg , about 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, and about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once a week.

[0221] In some embodiments, nipocalimab is administered at a dose of about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, or about 25 mg / kg. g, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg , about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, About 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg, about 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 7 and administered once every two weeks at a dose of 7 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0222] In some embodiments, nipocalimab is administered at a dose of about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, or about 25 mg / kg. g, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg , about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, About 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg, about 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 7 about 7 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg administered once every three weeks.

[0223] In some embodiments, nipocalimab is administered at a dose of about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, or about 25 mg / kg. g, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg , about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, About 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg, about 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 7 about 7 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg administered once every four weeks.

[0224] In some embodiments, nipocalimab is administered at about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / k g, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg , about 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, and about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once a month.

[0225] In some embodiments, the FcRn antagonist is orilanolimab. In some embodiments, orilanolimab is administered subcutaneously or intravenously. In some embodiments, orilanolimab is administered at a dose of about 0.2 mg / kg to about 200 mg / kg, or at a fixed dose of about 20 mg to about 20,000 mg, once per week, once every 2 weeks, once every 3 weeks, once every 4 weeks, once per month, or once every 6 weeks.

[0226] In some embodiments, orilanolimab is administered at a dose of about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / kg kg, about 38mg / kg, about 39mg / kg, about 40mg / kg, about 41mg / kg, about 42mg / kg, about 43mg / kg, about 44mg / kg, about 45mg / kg, about 46mg / kg, about 47mg / kg, about 48mg / kg, about 49mg / kg, about 50mg / k g, about 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, and about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once a week.

[0227] In some embodiments, orilanolimab is administered at a dose of about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, or about 25 mg / kg. kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / k g, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg , about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 mg / kg, About 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about and administered once every two weeks at a dose of 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0228] In some embodiments, orilanolimab is administered at a dose of about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, or about 25 mg / kg. kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / k g, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg , about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 mg / kg, About 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about and administered once every three weeks at a dose of 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0229] In some embodiments, orilanolimab is administered at a dose of about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, or about 25 mg / kg. kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / k g, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg , about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about 62 mg / kg, about 63 mg / kg, About 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about and administered once every four weeks at a dose of 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0230] In some embodiments, orilanolimab is administered at a dose of about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / kg kg, about 38mg / kg, about 39mg / kg, about 40mg / kg, about 41mg / kg, about 42mg / kg, about 43mg / kg, about 44mg / kg, about 45mg / kg, about 46mg / kg, about 47mg / kg, about 48mg / kg, about 49mg / kg, about 50mg / k g, about 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, and about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once a month.

[0231] In some embodiments, orilanolimab is administered intravenously at a dose of about 30 mg / kg once a week for three weeks, then at a dose of 10 mg / kg every other week.

[0232] In some embodiments, the FcRn antagonist is batoclimab. In some embodiments, batoclimab is administered subcutaneously or intravenously. In some embodiments, batoclimab is administered at a dose of about 0.2 mg / kg to about 200 mg / kg, or at a fixed dose of about 20 mg to about 20,000 mg, once per week, once every 2 weeks, once per 3 weeks, once per 4 weeks, once per month, or once per 6 weeks.

[0233] In some embodiments, batoclimab is administered at a dose of about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, or about 25 mg / kg. kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / k g, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg , about 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, and about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once a week.

[0234] In some embodiments, batoclimab is administered at a dose of about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg. g, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg , about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, About 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg, about 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 7 and administered once every two weeks at a dose of 7 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg.

[0235] In some embodiments, batoclimab is administered at a dose of about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg. g, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg , about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, About 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg, about 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 7 about 7 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg administered once every three weeks.

[0236] In some embodiments, batoclimab is administered at a dose of about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg. g, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg , about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, About 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg, about 64mg / kg, about 65mg / kg, about 66mg / kg, about 67mg / kg, about 68mg / kg, about 69mg / kg, about 70mg / kg, about 71mg / kg, about 72mg / kg, about 73mg / kg, about 74mg / kg, about 75mg / kg, about 76mg / kg, about 7 about 7 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg administered once every four weeks.

[0237] In some embodiments, batoclimab is administered at a dose of about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 12.5 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, or about 25 mg / kg. kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / k g, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg , about 51mg / kg, about 52mg / kg, about 53mg / kg, about 54mg / kg, about 55mg / kg, about 56mg / kg, about 57mg / kg, about 58mg / kg, about 59mg / kg, about 60mg / kg, about 61mg / kg, about 62mg / kg, about 63mg / kg , about 64 mg / kg, about 65 mg / kg, about 66 mg / kg, about 67 mg / kg, about 68 mg / kg, about 69 mg / kg, about 70 mg / kg, about 71 mg / kg, about 72 mg / kg, about 73 mg / kg, about 74 mg / kg, about 75 mg / kg, about 76 mg / kg, and about 77 mg / kg, about 78 mg / kg, about 79 mg / kg, about 80 mg / kg, about 81 mg / kg, about 82 mg / kg, about 83 mg / kg, about 84 mg / kg, about 85 mg / kg, about 86 mg / kg, about 87 mg / kg, about 88 mg / kg, about 89 mg / kg, about 90 mg / kg, about 91 mg / kg, about 92 mg / kg, about 93 mg / kg, about 94 mg / kg, about 95 mg / kg, about 96 mg / kg, about 97 mg / kg, about 98 mg / kg, about 99 mg / kg, or about 100 mg / kg, administered once a month.

[0238] In some embodiments, the method further comprises administering to the subject a compound indicated as a standard of care for LN, hi some embodiments, the method further comprises administering to the subject an effective amount of one or more of the following compounds: glucocorticoid, mycophenolate mofetil (MMF), mycophenolic acid (MPA), an angiotensin-converting enzyme inhibitor (ACEi), an angiotensin receptor blocker (ARB), and / or hydroxychloroquine.

[0239] In one embodiment, the method further comprises administering to the subject an effective amount of a corticosteroid and / or an immunosuppressant. In one embodiment, the method further comprises administering to the subject an effective amount of a corticosteroid. In one embodiment, the method further comprises administering to the subject an effective amount of a glucocorticoid. In one embodiment, the method further comprises administering to the subject an effective amount of a glucocorticoid intravenously and / or administering to the subject an effective amount of a glucocorticoid orally. In one embodiment, the method further comprises administering to the subject an effective amount of a glucocorticoid intravenously and administering to the subject an effective amount of a glucocorticoid orally.

[0240] In one embodiment, the method further comprises administering to the subject an effective amount of prednisone. In one embodiment, the method further comprises administering to the subject prednisone at a dose of 7.5 mg / day to 75 mg / day, up to 1 mg / kg / day. In one embodiment, the method further comprises administering to the subject prednisone at a dose of 8 mg / day to 72 mg / day, up to 1 mg / kg / day. In one embodiment, the method further comprises administering to the subject prednisone at a dose of 9 mg / day to 66 mg / day, up to 1 mg / kg / day. In one embodiment, the method further comprises administering to the subject prednisone at a dose of 10 mg / day to 60 mg / day, up to 1 mg / kg / day. In one embodiment, the method further comprises administering to the subject prednisone at a dose of 0.5 mg / kg / day to 1 mg / kg / day. In one embodiment, the method further comprises administering to the subject prednisone at a dose of 0.6 mg / kg / day to 1 mg / kg / day. In one embodiment, the method further comprises administering to the subject prednisone at a dose of 0.6 mg / kg / day to 1 mg / kg / day, up to a maximum of 80 mg / day. In one embodiment, the prednisone is administered orally.

[0241] In one embodiment, the method further comprises administering to the subject an effective amount of methylprednisolone. In one embodiment, the method further comprises administering to the subject methylprednisolone at a dose of 100 mg to 1250 mg for up to three days. In one embodiment, the method further comprises administering to the subject methylprednisolone at a dose of 150 mg to 1200 mg for up to three days. In one embodiment, the method further comprises administering to the subject methylprednisolone at a dose of 200 mg to 1100 mg for up to three days. In one embodiment, the method further comprises administering to the subject methylprednisolone at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the method further comprises administering to the subject methylprednisolone at a dose of 0.25 g / day to 0.5 g / day. In one embodiment, the method further comprises administering to the subject methylprednisolone at a dose of 0.25 g / day to 0.5 g / day for 1 to 3 days. In one embodiment, the methylprednisolone is administered intravenously.

[0242] In one embodiment, the method further comprises orally administering to the subject an effective amount of prednisone and intravenously administering an effective amount of methylprednisolone. In one embodiment, the method further comprises orally administering to the subject prednisone at a dose of 10 mg / day to 60 mg / day, up to 1 mg / kg / day, and intravenously administering methylprednisolone at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the method further comprises orally administering to the subject prednisone at a dose of 0.5 mg / kg / day to 1 mg / kg / day, and intravenously administering methylprednisolone at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the method further comprises administering to the subject orally prednisone at a dose of 0.6 mg / kg / day to 1 mg / kg / day up to a maximum of 80 mg / day, and intravenously administering methylprednisolone at a dose of 0.25 g / day to 0.5 g / day for 1 to 3 days.

[0243] In one embodiment, the method further comprises administering to the subject an effective amount of cyclophosphamide. In one embodiment, the method further comprises administering to the subject an effective amount of cyclophosphamide for up to six months. In one embodiment, the method further comprises administering to the subject cyclophosphamide intravenously at a dose of 500 mg once every two weeks. In one embodiment, the method further comprises administering to the subject cyclophosphamide intravenously at a dose of 500 mg once every two weeks for six months. In one embodiment, the method further comprises administering to the subject cyclophosphamide intravenously at a dose of 0.5 g / m 2 ~1g / m 2 In one embodiment, the method further comprises orally administering cyclophosphamide to the subject at a dose of 0.5 g / m once a month. 2 ~1g / m 2 once a month for six months.

[0244] In one embodiment, the method further comprises administering to the subject an effective amount of a calcineurin inhibitor. In one embodiment, the method further comprises administering to the subject an effective amount of tacrolimus. In one embodiment, the method further comprises administering to the subject tacrolimus having a trough level of approximately 5.5 ng / mL (6.8 nmol / L). In one embodiment, the method further comprises administering to the subject tacrolimus having a trough level of approximately 5.5 ng / mL (6.8 nmol / L) and a mycophenolic acid analog. In one embodiment, the method further comprises administering to the subject tacrolimus having a trough level of approximately 5.5 ng / mL (6.8 nmol / L) and a mycophenolic acid analog for 24 months. In one embodiment, in a subject with a serum creatinine (SCr) level of less than 3 mg / dL (265 μmol / L), the method further comprises administering to the subject tacrolimus, wherein the trough level is approximately 5.5 ng / mL (6.8 nmol / L), and a mycophenolic acid analog for 24 months. In one embodiment, the method further comprises administering to the subject an effective amount of voclosporin. In one embodiment, the method further comprises administering to the subject voclosporin at a dose of 23.7 mg twice daily. In one embodiment, the method further comprises administering to the subject voclosporin at a dose of 23.7 mg twice daily and a mycophenolic acid analog. In one embodiment, the method further comprises administering to the subject voclosporin at a dose of 23.7 mg twice daily and a mycophenolic acid analog for 52 weeks. In one embodiment, the method further comprises administering to the subject voclosporin at a dose of 23.7 mg twice daily and a mycophenolic acid analog for 52 weeks. 2 In subjects with an eGFR greater than 45 mL / min per 100 ml, the method further comprises administering to the subject voclosporin at a dose of 23.7 mg twice daily and a mycophenolic acid analog for 52 weeks.

[0245] In one embodiment, when the subject is administered the FcRn antagonist, the dose of prednisone is reduced to a dose of 7.5 mg / day for 12 weeks.

[0246] In one embodiment, the method further comprises administering to the subject an effective amount of mycophenolate mofetil (MMF), mycophenolic acid (MPA), or an analog thereof. In one embodiment, the method further comprises administering to the subject a daily dose of MMF, MPA, or an analog thereof. In one embodiment, the dose of MMF or MPA is increased to a maximum of 1.5 g or 2 g per day, or the equivalent, in divided doses within four weeks. In one embodiment, the method further comprises orally administering to the subject MMF at a dose of 1 g to 1.5 g twice daily. In one embodiment, the method further comprises orally administering to the subject mycophenolate sodium at a dose of 0.72 g to 1.08 g twice daily.

[0247] In one embodiment, the method further comprises administering to the subject an effective amount of a B-lymphocyte-targeted biologic. Examples of B-lymphocyte-targeted biologics include, but are not limited to, belimumab, rituximab, and obinutuzumab. In one embodiment, the method further comprises administering to the subject an effective amount of belimumab. In one embodiment, the method further comprises intravenously administering to the subject belimumab at a dose of 10 mg / kg once every two weeks for three doses, then once every four weeks for subsequent doses. In one embodiment, the method further comprises intravenously administering to the subject belimumab at a dose of 10 mg / kg once every two weeks for three doses, then once every four weeks for subsequent doses, and administering a mycophenolic acid analog. In one embodiment, the method further comprises administering to the subject intravenously belimumab at a dose of 10 mg / kg once every two weeks for three doses, then once every four weeks for subsequent doses, and administering cyclophosphamide. In one embodiment, the method further comprises administering to the subject intravenously belimumab at a dose of 10 mg / kg once every two weeks for three doses, then once every four weeks for subsequent doses, and administering cyclophosphamide at a dose of 500 mg once every two weeks for six months. In one embodiment, the method further comprises administering to the subject an effective amount of rituximab. In one embodiment, the method further comprises administering to the subject rituximab at a dose of 1 g on days 1 and 15 as add-on therapy for refractory cases or corticosteroid minimization. In one embodiment, the method further comprises administering to the subject an effective amount of obinutuzumab.

[0248] In some embodiments, the FcRn antagonist is administered intravenously once every two weeks along with MMF or MPA and glucocorticoid treatment for 52 weeks, hi some embodiments, the FcRn antagonist is efgartigimod.

[0249] In one embodiment, the method further comprises administering to the subject an effective amount of an ACEi or ARB.

[0250] In one embodiment, the method further comprises administering to the subject an effective amount of hydroxychloroquine. In some embodiments, the maximum dose of hydroxychloroquine is 5 mg / kg / day. In one embodiment, the hydroxychloroquine is administered for 24 weeks. In one embodiment, the hydroxychloroquine is administered for at least 24 weeks.

[0251] In one embodiment, the subject has previously been treated with induction therapy for LN. In one embodiment, the subject has received induction therapy for LN. In one embodiment, the induction therapy is initiated within 60 days prior to administering the FcRn antagonist to the subject. In one embodiment, the induction therapy is initiated less than 60 days prior to administering the FcRn antagonist to the subject. In one embodiment, the induction therapy is initiated at least 3 days but not more than 60 days (e.g., 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60 days) prior to administering the FcRn antagonist to the subject. In one embodiment, the subject has received induction therapy within 60 days prior to administering the FcRn antagonist to the subject. In one embodiment, the method comprises administering an effective amount of a human FcRn antagonist to the subject after the subject has received induction therapy for LN. In one embodiment, the method comprises administering to the subject an effective amount of a human FcRn antagonist within 60 days of the subject receiving induction therapy for LN.

[0252] In one embodiment, the subject has been previously treated with an effective amount of a corticosteroid and / or an immunosuppressant. In one embodiment, the subject has been previously treated with prednisone. In one embodiment, the induction therapy comprises administering to the subject an effective amount of a corticosteroid and / or an immunosuppressant. In one embodiment, the induction therapy comprises administering to the subject an effective amount of a corticosteroid. In one embodiment, the induction therapy comprises administering to the subject an effective amount of a glucocorticoid. In one embodiment, the induction therapy comprises administering to the subject an effective amount of a glucocorticoid intravenously and / or administering to the subject an oral glucocorticoid. In one embodiment, the induction therapy comprises administering to the subject an effective amount of a glucocorticoid intravenously and administering to the subject an oral glucocorticoid.

[0253] In one embodiment, the subject has been previously treated with an effective amount of prednisone. In one embodiment, the subject has been previously treated with prednisone at a dose of 7.5 mg / day to 75 mg / day, up to 1 mg / kg / day. In one embodiment, the subject has been previously treated with prednisone at a dose of 8 mg / day to 72 mg / day, up to 1 mg / kg / day. In one embodiment, the subject has been previously treated with prednisone at a dose of 9 mg / day to 66 mg / day, up to 1 mg / kg / day. In one embodiment, the subject has been previously treated with prednisone at a dose of 10 mg / day to 60 mg / day, up to 1 mg / kg / day. In one embodiment, the subject has been previously treated with prednisone at a dose of 0.6 mg / kg / day to 1 mg / kg / day. In one embodiment, the method further comprises administering prednisone to the subject at a dose of 0.6 mg / kg / day to 1 mg / kg / day, up to 80 mg / day. In one embodiment, the induction therapy comprises administering to the subject an effective amount of prednisone. In one embodiment, the induction therapy comprises administering to the subject prednisone at a dose of 7.5 mg / day to 75 mg / day, up to a maximum of 1 mg / kg / day. In one embodiment, the induction therapy comprises administering to the subject prednisone at a dose of 8 mg / day to 72 mg / day, up to a maximum of 1 mg / kg / day. In one embodiment, the induction therapy comprises administering to the subject prednisone at a dose of 9 mg / day to 66 mg / day, up to a maximum of 1 mg / kg / day. In one embodiment, the induction therapy comprises administering to the subject prednisone at a dose of 10 mg / day to 60 mg / day, up to a maximum of 1 mg / kg / day. In one embodiment, the induction therapy comprises administering to the subject prednisone at a dose of 0.5 mg / kg / day to 1 mg / kg / day. In one embodiment, the induction therapy comprises administering to the subject prednisone at a dose of 0.6 mg / kg / day to 1 mg / kg / day. In one embodiment, the method further comprises administering to the subject prednisone at a dose of 0.6 mg / kg / day to 1 mg / kg / day, up to a maximum of 80 mg / day. In one embodiment, the prednisone is administered orally.

[0254] In one embodiment, the subject has been previously treated with an effective amount of methylprednisolone. In one embodiment, the subject has been previously treated with methylprednisolone at a dose of 100 mg to 1250 mg for up to three days. In one embodiment, the subject has been previously treated with methylprednisolone at a dose of 150 mg to 1200 mg for up to three days. In one embodiment, the subject has been previously treated with methylprednisolone at a dose of 200 mg to 1100 mg for up to three days. In one embodiment, the subject has been previously treated with methylprednisolone at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the subject has been previously treated with methylprednisolone at a dose of 0.25 g / day to 0.5 g / day. In one embodiment, the method further comprises administering to the subject methylprednisolone at a dose of 0.25 g / day to 0.5 g / day for one to three days. In one embodiment, the induction therapy comprises administering to the subject an effective amount of methylprednisolone. In one embodiment, the induction therapy comprises administering to the subject methylprednisolone at a dose of 100 mg to 1250 mg for up to three days. In one embodiment, the induction therapy comprises administering to the subject methylprednisolone at a dose of 150 mg to 1200 mg for up to three days. In one embodiment, the induction therapy comprises administering to the subject methylprednisolone at a dose of 200 mg to 1100 mg for up to three days. In one embodiment, the induction therapy comprises administering to the subject methylprednisolone at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the induction therapy comprises administering to the subject methylprednisolone at a dose of 0.25 g / day to 0.5 g / day. In one embodiment, the method further comprises administering to the subject methylprednisolone at a dose of 0.25 g / day to 0.5 g / day for 1 to 3 days. In one embodiment, the methylprednisolone is administered intravenously.

[0255] In one embodiment, the subject has been previously treated with effective amounts of oral prednisone and intravenous methylprednisolone. In one embodiment, the subject has been previously treated with oral prednisone at a dose of 10 mg / day to 60 mg / day up to 1 mg / kg / day and intravenous methylprednisolone at a dose of 500 mg to 1000 mg for up to 3 days. In one embodiment, induction therapy comprises administering oral prednisone and intravenous methylprednisolone to the subject. In one embodiment, the subject has been previously treated with oral prednisone at a dose of 0.6 mg / kg / day to 1 mg / kg / day up to 80 mg / day and intravenous methylprednisolone at a dose of 0.25 g / day to 0.5 g / day for 1 to 3 days. In one embodiment, the induction therapy comprises administering to the subject an effective amount of prednisone orally at a dose of 10 mg / day to 60 mg / day up to 1 mg / kg / day and methylprednisolone intravenously at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the induction therapy comprises administering to the subject an effective amount of prednisone orally at a dose of 0.5 mg / kg / day to 1 mg / kg / day and methylprednisolone intravenously at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the induction therapy comprises administering to the subject an effective amount of prednisone orally at a dose of 0.6 mg / kg / day to 1 mg / kg / day up to 80 mg / day and methylprednisolone intravenously at a dose of 0.25 g / day to 0.5 g / day for one to three days.

[0256] In one embodiment, the subject has been previously treated with an effective amount of cyclophosphamide. In one embodiment, the subject has been previously treated with an effective amount of cyclophosphamide for up to six months. In one embodiment, the subject has been previously treated with intravenous cyclophosphamide at a dose of 500 mg once every two weeks. In one embodiment, the subject has been previously treated with intravenous cyclophosphamide at a dose of 500 mg once every two weeks for six months. In one embodiment, the subject has been previously treated with oral cyclophosphamide at a dose of 0.5 g / m 2 ~1g / m 2 In one embodiment, the subject was previously treated with oral cyclophosphamide at a dose of 0.5 g / m once a month.2 ~1g / m 2 once a month for six months. In one embodiment, the induction therapy comprises administering to the subject an effective amount of cyclophosphamide. In one embodiment, the induction therapy comprises administering to the subject an effective amount of cyclophosphamide for up to six months. In one embodiment, the induction therapy comprises administering to the subject intravenously cyclophosphamide at a dose of 500 mg once every two weeks. In one embodiment, the induction therapy comprises administering to the subject intravenously cyclophosphamide at a dose of 500 mg once every two weeks for six months. In one embodiment, the induction therapy comprises administering to the subject intravenously cyclophosphamide at a dose of 0.5 g / m 2 ~1g / m 2 In one embodiment, induction therapy comprises administering cyclophosphamide orally to a subject at a dose of 0.5 g / m once a month. 2 ~1g / m 2 This involves oral administration of the drug at a dose of 0.01 mg once a month for six months.

[0257] In one embodiment, the subject was previously treated with an effective amount of a calcineurin inhibitor. In one embodiment, the method further comprises administering to the subject an effective amount of tacrolimus. In one embodiment, the subject was previously treated with tacrolimus having a trough level of approximately 5.5 ng / mL (6.8 nmol / L). In one embodiment, the subject was previously treated with tacrolimus having a trough level of approximately 5.5 ng / mL (6.8 nmol / L) and a mycophenolic acid analog. In one embodiment, the subject was previously treated with tacrolimus having a trough level of approximately 5.5 ng / mL (6.8 nmol / L) and a mycophenolic acid analog for 24 months. In one embodiment, in subjects with SCr levels less than 3 mg / dL (265 μmol / L), the subject has been previously treated with tacrolimus, with a trough level of approximately 5.5 ng / mL (6.8 nmol / L), and a mycophenolic acid analog for 24 months. In one embodiment, the subject has been previously treated with an effective amount of voclosporin. In one embodiment, the subject has been previously treated with voclosporin at a dose of 23.7 mg twice daily. In one embodiment, the subject has been previously treated with voclosporin at a dose of 23.7 mg twice daily and a mycophenolic acid analog. In one embodiment, the subject has been previously treated with voclosporin at a dose of 23.7 mg twice daily and a mycophenolic acid analog for 52 weeks. In one embodiment, the subject has been previously treated with voclosporin at a dose of 23.7 mg twice daily and a mycophenolic acid analog for 52 weeks. In one embodiment, the subject has been previously treated with 1.73 mg twice daily. 2In subjects with an eGFR greater than 45 mL / min per 1000 mg / day, the subject was previously treated with voclosporin at a dose of 23.7 mg twice daily and a mycophenolic acid analog for 52 weeks. In one embodiment, the induction therapy comprises administering to the subject an effective amount of a calcineurin inhibitor. In one embodiment, the method further comprises administering to the subject an effective amount of tacrolimus. In one embodiment, the induction therapy comprises administering to the subject tacrolimus having a trough level of approximately 5.5 ng / mL (6.8 nmol / L). In one embodiment, the induction therapy comprises administering to the subject tacrolimus having a trough level of approximately 5.5 ng / mL (6.8 nmol / L) and a mycophenolic acid analog. In one embodiment, the induction therapy comprises administering to the subject tacrolimus, where the trough level is approximately 5.5 ng / mL (6.8 nmol / L), and a mycophenolic acid analog for 24 months. In one embodiment, in a subject with an SCr level of less than 3 mg / dL (265 μmol / L), the induction therapy comprises administering to the subject tacrolimus, where the trough level is approximately 5.5 ng / mL (6.8 nmol / L), and a mycophenolic acid analog for 24 months. In one embodiment, the induction therapy comprises administering to the subject an effective amount of voclosporin. In one embodiment, the induction therapy comprises administering to the subject voclosporin at a dose of 23.7 mg twice daily. In one embodiment, the induction therapy comprises administering to the subject voclosporin at a dose of 23.7 mg twice daily and a mycophenolic acid analog. In one embodiment, induction therapy comprises administering to a subject voclosporin at a dose of 23.7 mg twice daily and a mycophenolic acid analog for 52 weeks. 2 In subjects with an eGFR greater than 45 mL / min per 100 ml, induction therapy involves administering to the subject voclosporin at a dose of 23.7 mg twice daily and a mycophenolic acid analog for 52 weeks.

[0258] In one embodiment, when a subject is administered an FcRn antagonist, the dose of prednisone is tapered to a dose of 7.5 mg / day over 12 weeks. In one embodiment, the initial oral prednisone dose is 0.5 mg / kg / day to 1 mg / kg / day, not to exceed 60 mg / day. In one embodiment, the initial oral prednisone dose is rounded to the nearest 10 mg increment as set forth in Table S2, and prednisone tapering is initiated two weeks after initiation of oral prednisone according to the schedule set forth in Table S2. In some embodiments, for subjects administered an FcRn antagonist who experience an LN flare, the subject may receive post-LN flare prednisone at a dose of 0.5 mg / kg / day to 1 mg / kg / day, but not to exceed 60 mg / day, for two weeks. In one embodiment, post-LN flare prednisone is tapered to a dose of 10 mg / day or less within six weeks. In one embodiment, post-LN flare prednisone is tapered to a dose of 10 mg / day or less within 6 weeks according to the schedule set forth in Table S3. In some embodiments, for subjects receiving an FcRn antagonist who experience an extrarenal flare, the subject may receive extrarenal post-flare prednisone at a dose of up to 1 mg / kg / day, but not more than 60 mg / day. In one embodiment, post-renal flare prednisone is tapered to a dose of 7.5 mg / day over approximately 12 weeks. In one embodiment, post-renal flare prednisone is tapered to a dose of 7.5 mg / day over approximately 12 weeks according to the schedule set forth in Table S4.

[0259] In one embodiment, the subject has been previously treated with an effective amount of MMF, MPA, or an analog thereof. In one embodiment, the induction therapy comprises administering to the subject an effective amount of MMF, MPA, or an analog thereof. In one embodiment, the dose of MMF or MPA is increased within 4 weeks to a maximum of 1.5 g or 2 g / day, or the equivalent, in divided doses. In one embodiment, the subject has been previously treated with oral MMF at a dose of 1 g to 1.5 g twice daily. In one embodiment, the subject has been previously treated with oral mycophenolate sodium at a dose of 0.72 g to 1.08 g twice daily. In one embodiment, the induction therapy comprises orally administering to the subject MMF at a dose of 1 g to 1.5 g twice daily. In one embodiment, the induction therapy comprises orally administering to the subject mycophenolate sodium at a dose of 0.72 g to 1.08 g twice daily. In one embodiment, the method further comprises administering to the subject a daily dose of an effective amount of MMF, MPA, or an analog thereof, hi one embodiment, the dose of MMF, MPA, or an analog thereof is increased within 4 weeks to a maximum of 1.5 g or 2 g / day or the equivalent in divided doses.

[0260] In one embodiment, the subject has been previously treated with an effective amount of a B-lymphocyte-targeted biologic. Examples of B-lymphocyte-targeted biologics include, but are not limited to, belimumab, rituximab, and obinutuzumab. In one embodiment, the subject has been previously treated with an effective amount of belimumab. In one embodiment, the subject has been previously treated with intravenous belimumab at a dose of 10 mg / kg once every two weeks for three doses, then once every four weeks for subsequent doses. In one embodiment, the subject has been previously treated with intravenous belimumab at a dose of 10 mg / kg once every two weeks for three doses, then once every four weeks for subsequent doses, and has been previously treated with a mycophenolic acid analog. In one embodiment, the subject has been previously treated with intravenous belimumab at a dose of 10 mg / kg once every two weeks for three doses, then once every four weeks for subsequent doses, and has been previously treated with cyclophosphamide. In one embodiment, the subject was previously treated with intravenous belimumab at a dose of 10 mg / kg once every two weeks for three doses, then once every four weeks for subsequent doses, and cyclophosphamide at a dose of 500 mg once every two weeks for six months. In one embodiment, the subject was previously treated with an effective amount of rituximab. In one embodiment, the subject was previously treated with rituximab at a dose of 1 g on days 1 and 15 as add-on therapy for refractory cases or corticosteroid minimization. In one embodiment, the subject was previously treated with an effective amount of obinutuzumab.

[0261] In one embodiment, the induction therapy comprises administering to the subject an effective amount of a B-lymphocyte-targeted biologic. Examples of B-lymphocyte-targeted biologics include, but are not limited to, belimumab, rituximab, and obinutuzumab. In one embodiment, the induction therapy comprises administering to the subject an effective amount of belimumab. In one embodiment, the induction therapy comprises administering to the subject intravenously belimumab at a dose of 10 mg / kg once every two weeks for three doses, then once every four weeks for subsequent doses. In one embodiment, the induction therapy comprises administering to the subject intravenously belimumab at a dose of 10 mg / kg once every two weeks for three doses, then once every four weeks for subsequent doses, and administering a mycophenolic acid analog. In one embodiment, the induction therapy comprises administering to the subject intravenously belimumab at a dose of 10 mg / kg once every two weeks for three doses, then once every four weeks for subsequent doses, and cyclophosphamide. In one embodiment, the induction therapy comprises administering to the subject intravenously belimumab at a dose of 10 mg / kg once every two weeks for three doses, then once every four weeks for subsequent doses, and cyclophosphamide at a dose of 500 mg once every two weeks for six months. In one embodiment, the induction therapy comprises administering to the subject an effective amount of rituximab. In one embodiment, the induction therapy comprises administering to the subject rituximab at a dose of 1 g on days 1 and 15 as add-on therapy for refractory cases or corticosteroid minimization. In one embodiment, the induction therapy comprises administering to the subject an effective amount of obinutuzumab.

[0262] In one embodiment, the subject has been previously treated with an ACEi or an ARB. In one embodiment, the method further comprises administering to the subject an ACEi or an ARB.

[0263] In one embodiment, the subject has been previously treated with hydroxychloroquine at a maximum dose of 5 mg / kg / day. In one embodiment, the method further comprises administering hydroxychloroquine at a maximum dose of 5 mg / kg / day to the subject. In one embodiment, the hydroxychloroquine is administered for 24 weeks. In one embodiment, the hydroxychloroquine is administered for at least 24 weeks.

[0264] In some embodiments, treatment of LN is achieved by providing a subject with a blood flow of at least 25 mL / min / 1.73 m 2 In some embodiments, the subject is characterized by exhibiting an eGFR of at least 30 mL / min / 1.73 m 2 , at least 35 mL / min / 1.73 m 2 , at least 40 mL / min / 1.73 m 2 , at least 45 mL / min / 1.73 m 2 , at least 50 mL / min / 1.73 m 2 , at least 55 mL / min / 1.73 m 2 , at least 60 mL / min / 1.73 m 2 , at least 65 mL / min / 1.73 m 2 , at least 70 mL / min / 1.73 m 2 , at least 75 mL / min / 1.73 m 2 , at least 80 mL / min / 1.73 m 2 , at least 85 mL / min / 1.73 m 2 , at least 90 mL / min / 1.73 m 2 , at least 95 mL / min / 1.73 m 2 , at least 100 mL / min / 1.73 m 2 , at least 105 mL / min / 1.73 m 2 , at least 110 mL / min / 1.73 m 2 , at least 115 mL / min / 1.73 m 2 , at least 120 mL / min / 1.73 m 2 In some embodiments, the subject exhibits an eGFR of at least 60 mL / min / 1.73 m 2In some embodiments, treatment of LN is characterized by the subject exhibiting a decrease in eGFR of less than 20% compared to a baseline eGFR obtained from the subject before administering the FcRn antagonist. In some embodiments, the subject exhibits a decrease in eGFR of less than 15%, less than 10%, less than 5%, or less than 1% compared to a baseline eGFR obtained from the subject before administering the FcRn antagonist.

[0265] In some embodiments, after administering the FcRn antagonist to the subject, the subject has a blood flow of at least 60 mL / min / 1.73 m 2 In some embodiments, after administering an FcRn antagonist to the subject, the subject exhibits a post-administration eGFR that is reduced by less than 20% compared to a baseline eGFR obtained from the subject prior to administration of the FcRn antagonist. In some embodiments, the post-administration eGFR is measured 24 weeks after administering the FcRn antagonist to the subject. In some embodiments, the post-administration eGFR is measured 52 weeks after administering the FcRn antagonist to the subject.

[0266] In some embodiments, after administering the FcRn antagonist to the subject, the subject has a blood flow of at least 90 mL / min / 1.73 m 2 In some embodiments, after administering an FcRn antagonist to the subject, the subject exhibits a post-administration eGFR that is reduced by less than 10% compared to a baseline eGFR obtained from the subject prior to administration of the FcRn antagonist. In some embodiments, the post-administration eGFR is measured 24 weeks after administering the FcRn antagonist to the subject. In some embodiments, the post-administration eGFR is measured 52 weeks after administering the FcRn antagonist to the subject.

[0267] In some embodiments, treatment of LN is characterized by the subject exhibiting a UPCR of at most 0.5 mg / mg, hi some embodiments, the subject exhibits a UPCR of at most 0.45 mg / mg, 0.4 mg / mg, 0.35 mg / mg, 0.3 mg / mg, 0.25 mg / mg, 0.2 mg / mg, 0.15 mg / mg, or 0.1 mg / mg.

[0268] In some embodiments, treatment of LN is characterized by the subject exhibiting at least a 50% reduction in UPCR compared to a baseline UPCR obtained from the subject before administration of the FcRn antagonist, and if the baseline UPCR is at most 3 mg / mg, the post-administration UPCR is less than 1 mg / mg. In some embodiments, treatment of LN is characterized by the subject exhibiting at least a 50% reduction in UPCR compared to a baseline UPCR obtained from the subject before administration of the FcRn antagonist, and if the baseline UPCR is more than 3 mg / mg, the post-administration UPCR is less than 3 mg / mg.

[0269] In some embodiments, the treatment of LN is characterized by a reduction in circulating immune complexes. In some embodiments, the circulating immune complexes are selected from the group consisting of C3, C4, CH50, and C1q-bound circulating immune complexes. In some embodiments, the prevalence of circulating immune complexes is reduced by at least 10%, at least 25%, at least 50%, at least 75%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% after administration of one or more of the treatments described herein. In some embodiments, circulating immune complexes are undetectable in a subject after administration of one or more of the treatments described herein. In some embodiments, the treatment is administration of an effective amount of an FcRn antagonist. In some embodiments, the treatment is administration of an effective amount of efgartigimod.

[0270] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post-administration UPCR of at most 0.5 mg / mg. In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post-administration UPCR that is reduced by at least 50% compared to a baseline UPCR obtained from the subject before administering the FcRn antagonist, and if the baseline UPCR is at most 3 mg / mg, the post-administration UPCR is less than 1 mg / mg. In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post-administration UPCR that is reduced by at least 50% compared to a baseline UPCR obtained from the subject before administering the FcRn antagonist, and if the baseline UPCR is more than 3 mg / mg, the post-administration UPCR is less than 3 mg / mg. In some embodiments, the post-administration UPCR is measured 24 weeks after administering the FcRn antagonist to the subject. In some embodiments, post-administration UPCR is measured 52 weeks after administering the FcRn antagonist to the subject.

[0271] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a reduced post-administration Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K score compared to a baseline SLEDAI-2K score obtained from the subject before administering the FcRn antagonist. In some embodiments, the post-administration SLEDAI-2K score is measured 24 weeks after administering the FcRn antagonist to the subject. In some embodiments, the post-administration SLEDAI-2K score is measured 52 weeks after administering the FcRn antagonist to the subject.

[0272] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post-administration level of serum autoantibodies that is reduced compared to the baseline level of serum autoantibodies obtained from the subject before administering the FcRn antagonist. The post-administration level of serum autoantibodies is reduced by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% compared to the baseline level of serum autoantibodies obtained from the subject before administering the FcRn antagonist. In some embodiments, the post-administration level of serum autoantibodies is measured 24 weeks after administering the FcRn antagonist to the subject. In some embodiments, the post-administration level of serum autoantibodies is measured 52 weeks after administering the FcRn antagonist to the subject. In some embodiments, the serum autoantibodies are selected from the group consisting of anti-dsDNA, ANA, aCL, anti-Sm, and anti-C1q.

[0273] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post-administration level of serum complement that is reduced compared to the baseline level of serum complement obtained from the subject before administering the FcRn antagonist. The post-administration level of serum complement is reduced by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% compared to the baseline level of serum complement obtained from the subject before administering the FcRn antagonist. In some embodiments, the post-administration level of serum complement is measured 24 weeks after administering the FcRn antagonist to the subject. In some embodiments, the post-administration level of serum complement is measured 52 weeks after administering the FcRn antagonist to the subject. In some embodiments, the serum complement is selected from the group consisting of C3, C4, CH50, and C1q-bound circulating immune complexes.

[0274] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits reduced post-administration levels of circulating immune complexes compared to baseline levels of circulating immune complexes obtained from the subject before administering the FcRn antagonist. In some embodiments, the circulating immune complexes are selected from the group consisting of C3, C4, CH50, and C1q-bound circulating immune complexes. In some embodiments, the post-administration levels of circulating immune complexes are reduced by at least 10%, at least 25%, at least 50%, at least 75%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% compared to baseline levels of circulating immune complexes obtained from the subject before administering the FcRn antagonist. In some embodiments, the post-administration levels of circulating immune complexes are measured 24 weeks after administering the FcRn antagonist to the subject. In some embodiments, the post-administration levels of circulating immune complexes are measured 52 weeks after the subject has been administered the FcRn antagonist.

[0275] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post-administration level of serum IgG that is reduced compared to the baseline level of serum IgG obtained from the subject before administering the FcRn antagonist. In some embodiments, the post-administration level of serum IgG is reduced by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% compared to the baseline level of serum IgG obtained from the subject before administering the FcRn antagonist. In some embodiments, the post-administration level of serum IgG is measured 24 weeks after administering the FcRn antagonist to the subject. In some embodiments, the post-administration level of serum IgG is measured 52 weeks after administering the FcRn antagonist to the subject.

[0276] In some embodiments, after administering an FcRn antagonist to a subject, the level of albumin is not decreased compared to the baseline level of albumin in the subject after administration of the FcRn antagonist. In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post-administration level of albumin that is not decreased compared to the baseline level of albumin obtained from the subject before administering the FcRn antagonist. In one embodiment, an albumin reduction of less than about 1%, 2%, 3%, 4%, or 5% is observed compared to the baseline albumin level. In one embodiment, an albumin reduction of less than about 10% is observed compared to the baseline albumin level. In some embodiments, the post-administration level of albumin is measured 24 weeks after administering the FcRn antagonist to the subject. In some embodiments, the post-administration level of albumin is measured 52 weeks after administering the FcRn antagonist to the subject.

[0277] In some embodiments, after administering an FcRn antagonist to a subject, the level of serum albumin is not reduced compared to the baseline level of serum albumin in the subject after administration of the FcRn antagonist. In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post-administration level of serum albumin that is not reduced compared to the baseline level of serum albumin obtained from the subject before administering the FcRn antagonist. In one embodiment, a serum albumin reduction of less than about 1%, 2%, 3%, 4%, or 5% is observed compared to the baseline serum albumin level. In one embodiment, a serum albumin reduction of less than about 10% is observed compared to the baseline serum albumin level. In some embodiments, the post-administration level of serum albumin is measured 24 weeks after administering an FcRn antagonist to the subject. In some embodiments, the post-administration level of serum albumin is measured 52 weeks after administering an FcRn antagonist to the subject.

[0278] In one embodiment, the subject is any human or non-human animal. In one embodiment, the subject is a human or non-human mammal. In one embodiment, the subject is a human. In one embodiment, the subject is of Asian descent. [Example]

[0279] The following examples are offered by way of illustration and not by way of limitation.

[0280] Example 1 Investigating the efficacy of efgartigimod in reducing circulating immune complexes Although immune complexes are found in healthy individuals, their formation is elevated in autoimmune diseases and may be expected to partially drive and / or exacerbate their pathology. Efgartigimod is an engineered Fc fragment that inhibits FcRn function by outcompeting endogenous IgG binding, resulting in reduced IgG recycling and increased IgG degradation. Because the half-life of IgG-rich immune complexes can also be affected by FcRn biology, circulating immune complex (CIC) levels were investigated as part of an open-label, adaptive phase 2 trial of extended efgartigimod treatment in participants with mild-to-moderate pemphigus vulgaris (PV) or pemphigus foliaceus (PF) (ClinicalTrials.gov: NCT03334058, Maho-Vaillant M et al. Front Immunol (2022) 13:863095). Briefly, seven participants (seven PV) were treated for 15 weeks in Cohort 3, and 15 participants (eight PV, seven PF) were treated for up to 34 weeks in Cohort 4, as previously reported (Goebeler M et al. Br J Dermatol (2021) 186(3):429-39). PV or PF diagnosis was confirmed by positive direct immunofluorescence, positive indirect immunofluorescence, and / or Dsg-1 / 3 ELISA. Participants were either newly diagnosed or recurrent and had mild to moderate disease severity (Pemphigus Disease Area Index [PDAI] <45 at baseline). A screening period of up to 3 weeks preceded the treatment period, and a 10-week treatment-free follow-up period followed the treatment period. In Cohort 3, intravenous (IV) efgartigimod was administered at 10 mg / kg weekly for 4 weeks as induction, followed by biweekly for 12 weeks as maintenance. In Cohort 3, efgartigimod could be initiated as monotherapy or in combination with 20 mg / day prednisone at the investigator's discretion, and a prednisone taper could be initiated within the maintenance period. In Cohort 4, IV efgartigimod was administered at 25 mg / kg body weight weekly until EoC, defined as a time when no new lesions have developed for a minimum of 2 weeks and the majority, i.e., approximately 80%, of established lesions have healed.Participants were then dosed every other week. In Cohort 4, efgartigimod was initiated with concomitant prednisone (20 mg / day) in all newly diagnosed participants and participants with off-therapy relapse, or at tapered doses when relapse occurred. Oral prednisone doses could be tapered at EoC. No other systemic treatments for pemphigus were permitted during the study, but topical corticosteroids, analgesics, and supportive care to corticosteroid therapy (e.g., vitamin D, proton pump inhibitors, and specific diets) were allowed.

[0281] Suppression of CIC was measured in six participants with PV and six participants with PF who received extended efgartigimod treatment in cohorts 3 and 4 and achieved a sustained clinical response. These participants underwent IgG CIC analysis by C1q ELISA, which detects complement-fixing IgG antibodies (without providing information on the antigen specificity of CIC). Briefly, the CIC-C1q EIA kit (A001, Quidel) was used according to the manufacturer's protocol to detect the levels of C1q-associated IgG aggregates in the serum of selected participants at different time points. Expression levels were determined using calibrators provided by the kit. IgG CIC levels were considered clinically significant if they were 4.0 mg Eq / ml or higher.

[0282] Although four participants presented with elevated baseline CIC levels, a significant reduction in CIC was observed during efgartigimod treatment (Figure 1), consistent with the observed improvement in the participants' clinical status, demonstrating that efgartigimod treatment reduced CIC in pemphigus patients.

[0283] Example 2 A survey of the efficacy and safety of efgartigimod in Chinese patients with lupus nephritis (LN) Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease. LN is an inflammatory autoimmune disease of the kidney caused by SLE and is the most common and life-threatening manifestation of SLE.

[0284] In unselected patients with SLE, approximately 25% to 50% have signs or symptoms of kidney disease at the time of SLE onset, and approximately 40% to 60% of patients with SLE develop kidney complications during the course of the disease. In China, approximately half of patients with SLE have kidney complications.

[0285] In actively proliferating LN, induction therapy with mycophenolate mofetil (MMF) or mycophenolic acid (MPA) or low-dose intravenous (IV) cyclophosphamide (CYC), both combined with glucocorticoids, is currently recommended. Alternative regimens include treatment with MMF and calcineurin inhibitors (e.g., tacrolimus) and high-dose CYC. Subsequent maintenance therapy includes treatment with MMF or azathioprine without or with low-dose glucocorticoids. Despite aggressive immunosuppressive therapy, 10% to 30% of patients with LN still progress to end-stage renal disease (ESRD), the ultimate manifestation of LN. Furthermore, up to 60% of patients fail to achieve treatment goals with currently available treatment options.

[0286] Neonatal Fc receptors (FcRn) maintain a constant level of IgG in serum by rescuing IgG antibodies from lysosomal degradation after cellular uptake. Given efgartigimod's mechanism of action of reducing IgG levels, efgartigimod may benefit patients with LN. Furthermore, efgartigimod has been shown to reduce circulating immune complexes in patients with pemphigus (Example 1; Figure 1). Because LN is primarily caused by renal deposition of immune complexes, this provides further proof of concept for the treatment of LN and / or prevention of LN onset or progression with efgartigimod.

[0287] A. Study Design Overall Design This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of efgartigimod IV in Chinese patients with active LN.

[0288] The study will include a screening period of up to 4 weeks, a treatment period of 24 weeks, and a follow-up period of 8 weeks.

[0289] Approximately 60 participants who meet the eligibility criteria during the screening period will be randomly assigned in a 1:1 ratio to receive weekly efgartigimod IV or placebo, both in combination with standard of care (SoC; i.e., glucocorticoids and MMF / MPA), for 24 weeks. Randomization will be stratified according to LN renal biopsy class (class III / IV with V or class III / IV without V).

[0290] The primary endpoint is the change in UPCR from baseline to week 24. Secondary endpoints include additional efficacy endpoints, PK, PD, immunogenicity, biomarkers, safety, and quality of life (see Table S6).

[0291] One week after participants receive their last infusion of the Investigational Medicinal Product (IMP) (Week 24), eligible participants have the option to roll over into an optional open-label follow-up study, which aims to evaluate the long-term safety of efgartigimod in this patient population. Participants who do not participate in the open-label follow-up study will remain in the main study for 8 weeks of safety follow-up.

[0292] A Data Safety Monitoring Board (DSMB) will review all open-label safety data, including IgG levels, during the study.

[0293] Selection of primary endpoint Substantial evidence indicates that an early reduction in proteinuria, particularly within 6 to 12 months of initiating treatment, is the single best predictor of improved long-term outcomes, including reduced risk of disease flares, ESRD, and death. Therefore, proteinuria or UPCR is a useful parameter for assessing the efficacy of treatment and is a preferred outcome measure by regulatory agencies.

[0294] An early reduction in UPCR indicates a long-term benefit in treating LN, which supports the use of an early reduction in UPCR as the primary endpoint in this study.

[0295] Rationale for placebo control Considering that SoC (glucocorticoids and immunosuppression with MMF / MPA) is administered in addition to placebo, this placebo-controlled study design is acceptable for this patient population. Placebo-controlled studies without SoC in patients with LN represent inappropriate therapy for a population at risk for severe renal damage and potential ESRD.

[0296] Dosage justification Based on results from previous clinical studies, including a Phase 3 study in patients with generalized myasthenia gravis (gMG), administration of 10 mg / kg efgartigimod IV q7d for four infusions achieved near-maximal reduction in total IgG, which resulted in a reduction in pathogenic autoantibodies and was associated with clinical efficacy in patients with gMG. Furthermore, this dose has been well tolerated in all populations tested to date, without safety concerns.

[0297] Patients with LN may have some degree of renal dysfunction and / or nephrotic proteinuria. Efgartigimod has a molecular weight of approximately 54 kDa and is therefore on the border of molecules that are renally filtered. Following a single 10 mg / kg efgartigimod IV dose in healthy subjects, less than 0.1% of the administered dose was recovered in the urine. A population covariate analysis approach was used to evaluate the potential effect of eGFR as a marker of renal function on the pharmacokinetic profile of efgartigimod. A statistically significant decrease in clearance with decreasing eGFR was identified, resulting in increased exposure. However, multiple IV doses up to 25 mg / kg were well tolerated in healthy volunteers. Therefore, a weekly IV dose of 10 mg / kg was selected for this study to achieve the maximum pharmacodynamic (IgG-reducing) effect in this population.

[0298] B. Study Population Anticipatory approval of protocol deviations from recruitment and enrollment criteria, also known as protocol waivers or exemptions, is not permitted.

[0299] Inclusion criteria Participants were eligible for study inclusion only if all of the following criteria applied: - At least 18 years of age at the time of signing the informed consent document; -Able to provide signed informed consent, including compliance with the requirements and limitations listed in the informed consent document and this protocol; -Diagnosis of SLE according to the 2012 classification criteria of the Systemic Lupus Erythematosus International Collaborating Clinic (SLICC); Active proliferative LN class III or IV [excluding class III(C), IV-S(C), and IV-G(C)] using the 2003 International Society of Nephrology (ISN) / Renal Pathology Society (RPS) criteria, with either the presence or absence of class V, as proven by renal biopsy within 6 months prior to randomization and confirmed by a central biopsy review group; - Requires LN induction therapy (glucocorticoids and MMF / MPA) based on the investigator's clinical judgment. Induction therapy may begin before screening but should begin no later than 60 days before randomization; - A positive antinuclear antibody (ANA) test result at screening, defined as an ANA titer of 1:80 or greater (based on Hep-2 immunofluorescence assay or enzyme immunoassay equivalent); - Meet at least one of the following criteria at screening: Elevated anti-dsDNA (30 IU / mL or more), b. Low complement levels (C3 less than 0.9 g / L or C4 less than 0.1 g / L); - Urinary protein creatinine ratio (UPCR) of 1.0 mg / mg or greater at screening; At screening, 60 mL / min / 1.73 m 2 estimated glomerular filtration rate (eGFR) greater than or equal to; Serum total IgG ≥ 6 g / L at screening. Eligibility for participants with total IgG 4-6 g / L at screening requires case-by-case discussion with the sponsor's medical monitor; Contraceptive use by non-sterilized male participants and women of childbearing potential (WOCBP) will be consistent with local regulations, if available, for individuals participating in clinical studies. WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline to establish non-pregnant status prior to receipt of the investigational medicinal product (IMP).

[0300] Exclusion criteria Participants will be excluded from the study if any of the following criteria apply: -Active or chronic infections requiring treatment, including: a. Any current therapy for chronic infections, including but not limited to tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, varicella zoster, or atypical mycobacteria; b. Any type of active infection (excluding fungal infections of the nail bed) or any major episode of infection requiring hospitalization or parenteral (IV or intramuscular) antibiotic treatment (e.g., antibacterial, antiviral, antifungal, or antiparasitic) within 60 days prior to randomization, or requiring oral antibiotics within 2 weeks prior to randomization; - Any evidence of central nervous system (CNS) lupus (including but not limited to seizures, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis, or CNS vasculitis); -Current renal dialysis or anticipated need for dialysis during the study period; - Previous kidney transplant or planned transplant during the study period; - History of malignancy if not considered cured by adequate treatment and without evidence of recurrence ≥3 years prior to randomization. The following cancers are not exclusionary: Adequately treated basal cell or squamous cell skin cancer, b. Cervical intraepithelial neoplasia, C. Carcinoma in situ of the breast, d. Incidental histologic findings of prostate cancer (TNM stage T1a or T1b); Heart failure due to SLE (New York Heart Association [NYHA] class III or IV) or any other severe cardiovascular comorbidity that poses safety concerns as judged by the investigator; - Any other known autoimmune disease that, in the investigator's opinion, interferes with the accurate assessment of clinical symptoms of SLE / LN or poses undue risk to the participant; - Clinical evidence of other significant or uncontrolled serious illness (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, or neurological), recent major surgery, or any other condition that, in the investigator's opinion, may confound the results of the study or pose undue risk to participants; - Previous unsuccessful treatment with MMF or any form of mycophenolate-based induction therapy, in the opinion of the investigator; - Use of systemic glucocorticoids within 12 months prior to randomization for a chronic condition (e.g., asthma, Crohn's disease) excluding SLE; Use of any monoclonal antibody within 3 months prior to randomization; - Previous treatment with plasma exchange within 3 months prior to randomization; - Receipt of CYC and / or CNI within 2 months prior to randomization; Receipt of intravenous immunoglobulin (IVIg) within 4 weeks prior to randomization; Use of complementary therapies within 4 weeks prior to randomization, including traditional Chinese medicine, herbs, or procedures (e.g., acupuncture), which may potentially interfere with the participant's efficacy and safety as assessed by the investigator; - Receipt of live / live-attenuated vaccines within 28 days prior to randomization. Receipt of any inactivated, subunit, polysaccharide, or conjugate vaccines at any time prior to screening is not considered an exclusion. Participants are encouraged to be up-to-date on vaccination(s) prior to the first dose of IMP; - Previous participation in a clinical study with efgartigimod; Use of any investigational therapy within 3 months or 5 half-lives (whichever is longer) prior to randomization; - Positive serology test at screening for active viral infection with any of the following conditions: Hepatitis B virus (HBV), indicating acute or chronic infection, unless associated with a negative HBV DNA test in accordance with the recommendations of the Centers for Disease Control and Prevention; b. Hepatitis C virus (HCV) based on an HCV antibody assay when not associated with a negative HCV RNA test; c. HIV based on test results related to any of the following: (1) AIDS-defining condition or fewer than 200 cells / mm 3 CD4 count, (2) not being adequately treated with antiretroviral therapy; - A positive SARS-CoV-2 antigen-based test at screening. Testing is required regardless of whether the participant has been vaccinated; - serum total IgG less than 4 g / L at screening; - Evidence of unstable renal function defined as a >20% decrease in eGFR within 3 months prior to randomization; -Having any of the following laboratory values ​​at screening: alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST) greater than 3 × the upper limit of normal (ULN); b. Total bilirubin greater than 1.5 × ULN c.75×10 9 platelets less than / L, d.1.5×10 9 neutrophils less than / L, e. Hemoglobin less than 8 g / dL; Known hypersensitivity or contraindication to efgartigimod, any of the excipients in IMP, or SoC medications used in the study; - Current alcohol, drug, or medication abuse, or a history thereof (i.e., within 12 months prior to randomization), in the opinion of the investigator; - Pregnant or lactating women and those intending to become pregnant during study participation; Any condition or situation that, in the investigator's opinion, makes the participant unsuitable for the study.

[0301] C. IMP(s) and combination therapy An investigational medicinal product (IMP) is defined as an investigational intervention(s), marketed product(s), placebo, or medical device(s) intended to be administered to study participants according to a study protocol.

[0302] Administered IMP(s) The IMPs in this study included efgartigimod IV and a matching placebo (with the same formulation but without the active ingredient of efgartigimod) as listed in Table S1. [Table 7]

[0303] Any medications or vaccinations (including non-prescription or prescription medicines, vitamins, and / or herbal supplements) that the participant receives within 30 days of signing the Informed Consent Document (ICF) or during study participation must be recorded.

[0304] Additionally, record the participant's vaccination history within the 12 months prior to signing of the ICF, including any vaccination(s) for COVID-19, and record the vaccine brand name and vaccination date, if known.

[0305] Any questions regarding concomitant or prior therapy should be contacted by the sponsor's medical monitor.

[0306] All participants will receive glucocorticoids as part of induction therapy for LN (see inclusion criteria). A combination of IV and oral glucocorticoids will be permitted, and an initial IV pulse / bolus of methylprednisolone will be completed prior to randomization. The IV methylprednisolone dosage for each participant will be determined based on the participant's clinical condition, with the guideline-recommended dosage (250 mg–500 mg / day for up to 3 days, allowing for flexible dosing depending on disease severity) serving as a reference.

[0307] All participants must be receiving oral prednisone at an equivalent dose of ≥10 mg / day to ≤60 mg / day (or 1.0 mg / kg / day, whichever is lower) at the time of randomization. Glucocorticoid tapering regimens will be specified per protocol and are described below.

[0308] An initial oral prednisone dose of 0.5-1.0 mg / kg / day is recommended, not to exceed 60 mg / day after intravenous methylprednisolone. Round the calculated dose to the nearest 10 mg increment listed in Table S2. Instruct participants to begin glucocorticoid tapering 2 weeks after initiation of oral glucocorticoids according to the schedule listed in Table S2. [Table 8]

[0309] For LN flare, participants were optionally treated with prednisone (0.5-1.0 mg / kg / day, but not more than 60 mg / day) for 2 weeks, followed by tapering of prednisone to achieve 10 mg / day or less within 6 weeks of initial glucocorticoid augmentation (see Table S3). [Table 9]

[0310] For extrarenal flares, participants will be optionally re-treated with prednisone at a maximum of 1.0 mg / kg / day (not to exceed 60 mg / day) based on disease severity, and participants will follow the recommended tapering schedule in Table S4. If gastrointestinal complications temporarily prevent oral glucocorticoid use, intravenous glucocorticoids at equivalent doses will be allowed. [Table 10]

[0311] All participants will either continue or begin treatment with MMF (or MPA) during screening as part of induction therapy for LN. MMF will be titrated up to a maximum of 1.5 g to 2 g / day (or equivalent) in divided doses within 4 weeks.

[0312] Participants who started LN induction therapy more than 60 days before randomization were ineligible if the previous induction was not completed or terminated more than 2 months before randomization, and reinduction was required per the investigator's discretion.

[0313] For participants taking angiotensin-converting enzyme inhibitors (ACEi) / angiotensin receptor blockers (ARB), the dose of ACEi and / or ARB should be kept stable throughout the treatment period.

[0314] All participants are strongly encouraged to receive hydroxychloroquine (maximum dose of 5 mg / kg / day) at the screening / baseline visit and during the treatment period. If no change is required due to safety / tolerability concerns, the hydroxychloroquine dose will be held stable.

[0315] At the investigator's discretion, bacterial prophylaxis will be initiated at randomization or at any time during the study in selected participants considered to be at high risk of developing an infection.

[0316] If renal function deteriorates (LN flare) during the treatment period as defined by any of the following, rescue therapy will be indicated at the investigator's discretion: A decrease in eGFR of more than 20% from baseline (confirmed by repeat testing) accompanied by at least one of the following: 24-hour UPCR and / or spot UPCR greater than 1.0 mg / mg, red blood cell casts, or white blood cell casts; and / or • Increase in 24-hour UPCR following: - If baseline UPCR is <3.5 mg / mg, an increase in 24-hour UPCR to ≥3.5 mg / mg and an increase in 24-hour UPCR of more than 2-fold the baseline value (confirmed by repeat testing or spot UPCR with an interval of no more than 2 weeks), - If baseline UPCR is ≥ 3.5 mg / mg, an increase in 24-hour UPCR of more than 2-fold the baseline value (confirmed by repeat testing or spot UPCR with an interval of ≤ 2 weeks).

[0317] In these situations, the investigator may increase the glucocorticoid dose. Participants will be treated with oral glucocorticoids at a prednisone dose of 0.5-1.0 mg / kg / day, but not more than 60 mg / day, for up to 2 weeks, followed by a prednisone taper to achieve a prednisone dose of 10 mg / day or less within 6 weeks of the start of the taper. Further tapers are at the investigator's discretion. Participants who do not respond to the initial 2-week course of increased glucocorticoids and then begin new immunosuppressive therapy (prohibited medications as defined in this study) will be considered treatment failures.

[0318] If a participant is at or at immediate risk of developing a severe form of lupus clinical condition (including, but not limited to, lupus encephalopathy, pulmonary hemorrhage, and lupus crisis), the participant will discontinue the IMP or discontinue the study at any time and receive clinically appropriate individualized treatment, at the investigator's discretion, in the participant's best interest.

[0319] Participants who experience an extrarenal SLE flare during the treatment period will optionally receive rescue therapy with additional oral glucocorticoids. An extrarenal SLE flare is defined as an increase in the SLEDAI-2K score not explained by hypocomplementemia or an increase in anti-dsDNA antibody levels, the initiation of new immunosuppressive therapy, or an increase in corticosteroids, as determined clinically appropriate by the investigator. The investigator should notify the sponsor's medical monitor of any clinical interventions for the flare. These participants will optionally be re-treated with prednisone (up to 1.0 mg / kg / day but not more than 60 mg / day, based on the investigator's judgment) for up to 2 weeks based on disease severity and organ system complications, and then the prednisone will be tapered to 10 mg / day or less according to a separate tapering schedule. If participants require new immunosuppressive therapy (other than glucocorticoids) for the treatment of the extrarenal SLE flare, they will be considered a treatment failure.

[0320] Prior to the initiation of rescue glucocorticoid therapy, all visit-related assessments will be completed, if possible, when increased disease activity is identified. If increased disease activity is identified between scheduled visits, participants will return to the clinic and all assessments listed for unscheduled visits due to increased lupus activity will be performed, including the following: One 24-hour urine collection for UPCR; ● Spot UPCR, ●SLEDAI-2K evaluation, Hematology, clinical chemistry, and urinalysis, ● Vital signs and physical examination (optional, simple physical examination at the researcher's discretion according to the participant's condition), Blood sample collection for PK, PD, and immunogenicity (pre-dose, if applicable); blood sample collection for biomarkers (pre-dose, if applicable); • Other evaluations at the discretion of the researcher.

[0321] Participants who initiate rescue therapy will continue IMP administration according to Table S5 or until criteria for discontinuation of IMP are met.

[0322] Participants will be allowed to receive corticosteroids for emerging illness (e.g., trauma, severe asthma) or surgery, if clinically justified. Corticosteroids will be provided to participants at the investigator's discretion to treat symptoms of adrenal insufficiency or steroid withdrawal. However, additional corticosteroid use in these scenarios should not exceed 2.5 mg / day for more than 7 days. In the event that surgery is required, participants will be instructed to notify the relevant clinical personnel at the participant's clinical study registration that the use of large doses of steroids will not be permitted. When possible, detailed surgical and anesthesia reports will be provided to the investigator for review. These reports will be maintained in the participant's medical record to document concomitant medications / therapy.

[0323] Prohibited drugs The following medications / treatments are prohibited: any investigational therapy within 3 months or 5 half-lives (whichever is longer) prior to randomization and during the treatment period; - any monoclonal antibody treatment within 3 months prior to randomization and during treatment; CYC within 2 months prior to randomization and during treatment, CNI within 2 months prior to randomization and during treatment, Complementary therapies, including traditional Chinese medicine, herbs, or procedures (e.g., acupuncture), within 4 weeks prior to randomization and during the treatment period, which, as assessed by the investigator, could potentially interfere with the participant's efficacy and safety; Live / live-attenuated vaccines within 28 days prior to randomization and during treatment, Other immunosuppressive medications not specifically allowed in the study will not be allowed during the study.

[0324] Limitations of concomitant drug therapy The following are limitations of concomitant drug therapy: - prescribed dose of MMF >3 g / day or prescribed dose of MPA >2160 mg / day at baseline and during treatment; Initiation of ACEi / ARB therapy during treatment Initiation of antimalarial treatment during treatment IV glucocorticoids for LN during the treatment period, [Table 11] TIFF2025537707000013.tif248170TIFF2025537707000014.tif248170TIFF2025537707000015.tif245170TIFF2025537707000016.tif246170

[0325] Urinary protein creatinine ratio (UPCR) UPCR (mg / mg) will be measured in a 24-hour urine sample, 2 x 24-hour urine samples, and a spot urine sample. See Table S5 for timing and instructions for urine sample collection. Participants will be provided with instructions regarding the procedure for collecting a 24-hour urine sample at home. Parameters include: ● Proteinuria, Urinary creatinine, ●UPCR.

[0326] SLEDAI-2K evaluation The SLEDAI-2K instrument will be used to assess SLE disease activity (see Table S5). Results of the following assessments are required for a complete SLEDAI-2K evaluation: • Proteinuria (based on a 24-hour urine collection); Platelets and white blood cells, - Microscopic examination of urinary casts, red blood cell count and white blood cell count in urine, ● Body temperature, • Anti-dsDNA, C3, C4, and CH50.

[0327] Circulating immune complex (CIC) assessment Blood samples will be collected according to the schedule listed in Table S5 and as detailed in the laboratory manual provided separately to the study site. CIC levels will be determined using a validated method.

[0328] Definition of clinical outcomes A complete renal response (CRR) is defined as: ●60mL / min / 1.73m 2 or greater than 20% reduction in eGFR from baseline eGFR value, and ● UPCR of 0.5 mg / mg or less, and • Criteria for treatment failure were not met.

[0329] Modified complete renal response (mCRR) is defined as: ●90mL / min / 1.73m 2 or greater than 10% eGFR or a confirmed decrease from baseline eGFR value, and ● UPCR of 0.5 mg / mg or less, and • Criteria for treatment failure were not met.

[0330] Partial renal response (PRR) is defined as: ●60mL / min / 1.73m 2 or greater than 20% reduction in eGFR from baseline eGFR value, and A decrease in UPCR of 50% or more from baseline, as follows: - If baseline UPCR is ≤3.0 mg / mg, UPCR <1.0 mg / mg; If baseline UPCR is >3.0 mg / mg, one of the following is met: UPCR <3.0 mg / mg; and • Criteria for treatment failure were not met.

[0331] Treatment failure was defined as: glucocorticoid doses >10 mg prednisone / day by week 24; or ●Receiving any of the following prohibited or restricted concomitant medications during the treatment period. - A prescribed dose of MMF greater than 3 g / day or a prescribed dose of MPA greater than 2160 mg / day, - Initiation of new immunosuppressive therapy for LN, including but not limited to CYC, CNI, rituximab, etc. -IV glucocorticoids for LN.

[0332] E. Pharmacokinetics Blood samples for PK analysis will be collected at the time points listed in Table S5. Efgartigimod serum concentrations will be determined using validated methods.

[0333] F. Pharmacodynamics Blood samples for determination of serum total IgG levels for PD assessment will be collected at the time points listed in Table S5. Total IgG levels will be determined using a validated method.

[0334] G. Biomarkers Blood samples will be collected for biomarker studies according to the schedule described in Table S5 and as detailed in the laboratory manual provided separately to the study site.

[0335] Biomarkers include: ●Autoantibodies (anti-dsDNA, ANA, aCL, anti-Sm, and anti-C1q), • Complement (C3, C4, CH50, and C1q-binding circulating immune complexes).

[0336] H. Immunogenicity Assessment Blood samples will be collected at the time points listed in Table S5 to assess serum levels of ADA to efgartigimod.

[0337] Samples are analyzed by a designated laboratory in a stepwise manner using a validated immunogenicity assay. Initially, samples are screened for a positive assay response (Step 1). Screened positive samples are then tested in a confirmatory assay (Step 2). Finally, a titration of the ADA response is performed on positive Step 2 samples to characterize the magnitude of the antibody response (Step 3).

[0338] I. Health Economics, or Health Resource Utilization and Health Economics Participants will complete the Health-Related Quality of Life Questionnaire (EQ-5D-5L) at scheduled time points shown in Table S5.

[0339] The EQ-5D-5L questionnaire is a standardized test recognized by many health authorities as a common measure of health status for clinical and economic evaluation. The descriptive system includes five items: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. Scores for each item include five levels: no problem, slight problem, moderate problem, considerable problem, and extreme problem.

[0340] A visual analog scale (VAS) is included within the EQ-5D-5L, where participants rate their health status from 0 (worst health you can imagine) to 100 (best health you can imagine). J. Objectives and Evaluation Items [Table 12] ***

[0341] The present invention is not limited in scope by the specific embodiments described herein. Indeed, various modifications of the invention in addition to those described will become apparent to those skilled in the art from the foregoing description and accompanying drawings. Such modifications are intended to fall within the scope of the appended claims.

Claims

1. A method of treating lupus nephritis in a subject in need thereof, comprising administering to said subject an effective amount of a human neonatal Fc receptor (FcRn) antagonist.

2. The method of claim 1 , wherein the FcRn antagonist comprises two, three, or four FcRn binding regions.

3. 3. The method of claim 1 or 2, wherein the FcRn antagonist comprises or consists of a variant Fc region or an FcRn-binding fragment thereof.

4. 4. The method of claim 3, wherein the variant Fc region or FcRn-binding fragment thereof binds to FcRn with higher affinity at pH 6.0 compared to the corresponding wild-type Fc region.

5. 5. The method of claim 3 or 4, wherein the variant Fc region or FcRn-binding fragment thereof binds to FcRn with higher affinity at pH 7.4 compared to the corresponding wild-type Fc region.

6. 6. The method of any one of claims 3 to 5, wherein the variant Fc region comprises or consists of a first Fc domain and a second Fc domain that form a homodimer or a heterodimer.

7. 7. The method of claim 6, wherein the first Fc domain and / or the second Fc domain comprises amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively.

8. 8. The method of claim 6 or 7, wherein the first Fc domain and / or the second Fc domain comprises amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

9. 9. The method of any one of claims 6 to 8, wherein the first Fc domain and / or the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, and SEQ ID NO:

30.

10. 10. The method of any one of claims 6 to 9, wherein the first Fc domain and the second Fc domain comprise amino acid sequences independently selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, and SEQ ID NO:

30.

11. The method of any one of claims 1 to 10, wherein the FcRn antagonist is efgartigimod.

12. The method of claim 1 , wherein the FcRn antagonist is an anti-FcRn antibody.

13. 13. The method of any one of claims 1 to 12, wherein the FcRn antagonist is administered to the subject at a fixed dose of 20 mg to 20,000 mg, or at a dose of 0.2 mg / kg to 200 mg / kg.

14. 14. The method of any one of claims 1 to 13, wherein the FcRn antagonist is administered intravenously at a dose of 10 mg / kg to 30 mg / kg once a week or once every two weeks.

15. 15. The method of any one of claims 1 to 14, wherein the FcRn antagonist is administered intravenously at a dose of 10 mg / kg once a week.

16. 13. The method of any one of claims 1 to 12, wherein the FcRn antagonist is administered subcutaneously at a fixed dose of 750 mg to 3000 mg once a week, once every two weeks, once every three weeks, once every four weeks, or once a month.

17. 17. The method of claim 16, wherein the FcRn antagonist is administered subcutaneously at a fixed dose of 1000 mg or 2000 mg once a week or once every two weeks.

18. The method of any one of claims 1 to 17, wherein the FcRn antagonist is administered for 52 weeks or less.

19. The method of any one of claims 1 to 18, wherein the FcRn antagonist is administered for 24 weeks or less.

20. The method of any one of claims 1 to 18, wherein the FcRn antagonist is administered for 24 weeks.

21. The method of any one of claims 1 to 18, wherein the FcRn antagonist is administered for at least 24 weeks.

22. The method of any one of claims 1 to 17, wherein the FcRn antagonist is administered for at least 52 weeks.

23. 23. The method of any one of claims 1-22, further comprising administering to the subject an effective amount of a glucocorticoid, mycophenolate mofetil (MMF), mycophenolic acid (MPA), an angiotensin-converting enzyme inhibitor (ACEi), an angiotensin receptor blocker (ARB), hydroxychloroquine, a B-lymphocyte targeting agent, or any combination thereof.

24. 24. The method of claim 23, wherein the glucocorticoid is methylprednisolone.

25. 25. The method of claim 24, wherein the methylprednisolone is administered intravenously once daily at a dose of 250 mg to 500 mg.

26. 25. The method of claim 23 or 24, wherein the methylprednisolone is administered daily for 1 to 3 days.

27. 27. The method of any one of claims 24 to 26, wherein the methylprednisolone is administered for three days.

28. 24. The method of claim 23, wherein the glucocorticoid is prednisone.

29. 29. The method of claim 28, wherein the prednisone is administered orally at a dose of 10 mg / day to 60 mg / day.

30. 30. The method of claim 28 or 29, wherein the prednisone is administered orally at a dose of 0.5 mg / kg / day to 1 mg / kg / day.

31. 31. The method of any one of claims 28-30, wherein the dose of prednisone is tapered to a dose of 7.5 mg / day over 12 weeks while the subject is administered the FcRn antagonist.

32. 24. The method of claim 23, wherein the MMF or MPA is administered daily.

33. 33. The method of claim 32, wherein the MMF or MPA is administered in a daily dose, and the daily dose is up-titrated to 1.5 g / day to 2 g / day in divided doses within 4 weeks.

34. 24. The method of claim 23, wherein the hydroxychloroquine is administered at a dose of up to 5 mg / kg / day.

35. 35. The method of claim 34, wherein the hydroxychloroquine is administered for 24 weeks.

36. 36. The method of claim 34 or 35, wherein the hydroxychloroquine is administered for at least 24 weeks.

37. 24. The method of claim 23, wherein the B lymphocyte targeting agent is selected from the group consisting of belimumab, rituximab, and obinutuzumab.

38. 1. A method of treating lupus nephritis in a subject in need thereof, comprising administering to the subject an effective amount of an FcRn antagonist within 60 days of the subject receiving induction therapy for lupus nephritis.

39. 39. The method of claim 38, wherein the induction therapy comprises administering to the subject an effective amount of a glucocorticoid.

40. 40. The method of claim 38 or 39, wherein the induction therapy comprises administering to the subject an effective amount of methylprednisolone.

41. 41. The method of claim 40, wherein the methylprednisolone is administered intravenously once daily at a dose of 250 mg to 500 mg.

42. 42. The method of claim 40 or 41, wherein the methylprednisolone is administered daily for 1 to 3 days.

43. 43. The method of any one of claims 40 to 42, wherein the methylprednisolone is administered for three days.

44. 44. The method of any one of claims 38-43, wherein the induction therapy comprises administering prednisone to the subject.

45. 45. The method of claim 44, wherein the prednisone is administered orally at a dose of 10 mg / day to 60 mg / day.

46. 46. ​​The method of claim 44 or 45, wherein the prednisone is administered orally at a dose of 0.5 mg / kg / day to 1 mg / kg / day.

47. 47. The method of any one of claims 44-46, wherein the dose of prednisone is tapered to a dose of 7.5 mg / day over 12 weeks while the subject is administered the FcRn antagonist.

48. 48. The method of any one of claims 38-47, wherein the induction therapy further comprises administering to the subject a daily dose of an effective amount of MMF or MPA.

49. 49. The method of claim 48, wherein the daily dose of MMF or MPA is up-titrated to 1.5 g / day to 2 g / day in divided doses within 4 weeks.

50. 50. The method of any one of claims 38-49, wherein the induction therapy further comprises administering to the subject an effective amount of a dose of hydroxychloroquine.

51. 51. The method of claim 50, wherein the dose of hydroxychloroquine is up to 5 mg / kg / day.

52. 52. The method of claim 50 or 51, wherein the hydroxychloroquine is administered for 24 weeks.

53. 52. The method of claim 50 or 51, wherein the dose of hydroxychloroquine is administered for at least 24 weeks.

54. 54. The method of any one of claims 38 to 53, wherein the induction therapy further comprises administering to the subject an effective amount of a B-lymphocyte targeting agent.

55. 55. The method of claim 54, wherein the B lymphocyte targeting agent is selected from the group consisting of belimumab, rituximab, and obinutuzumab.

56. After administering the FcRn antagonist to the subject, the subject has a blood flow rate of at least 60 mL / min / 1.73 m ２ 56. The method of any one of claims 1 to 55, wherein the estimated glomerular filtration rate (eGFR) after administration of

57. 56. The method of any one of claims 1-55, wherein, after administering the FcRn antagonist to the subject, the subject exhibits a post-administration eGFR that is reduced by less than 20% compared to a baseline eGFR obtained from the subject prior to administration of the FcRn antagonist.

58. 58. The method of claim 57, wherein the post-administration eGFR is measured 24 or 52 weeks after administering the FcRn antagonist to the subject.

59. After administering the FcRn antagonist to the subject, the subject has an IV flow of at least 90 mL / min / 1.73 m ２ 56. The method of any one of claims 1 to 55, wherein the estimated glomerular filtration rate (eGFR) after administration of

60. 56. The method of any one of claims 1-55, wherein, after administering the FcRn antagonist to the subject, the subject exhibits a post-administration eGFR that is reduced by less than 10% compared to a baseline eGFR obtained from the subject prior to administration of the FcRn antagonist.

61. 61. The method of claim 60, wherein the post-administration eGFR is measured 24 or 52 weeks after administering the FcRn antagonist to the subject.

62. 62. The method of any one of claims 1-61, wherein after administering the FcRn antagonist to the subject, the subject exhibits a post-dose urinary protein creatinine ratio (UPCR) of at most 0.5 mg / mg.

63. 59. The method of any one of claims 1-58, wherein, after administering the FcRn antagonist to the subject, the subject exhibits a post-administration UPCR that is reduced by at least 50% compared to a baseline UPCR obtained from the subject prior to administering the FcRn antagonist, and when the baseline UPCR is at most 3 mg / mg, the post-administration UPCR is less than 1 mg / mg.

64. 59. The method of any one of claims 1-58, wherein, after administering the FcRn antagonist to the subject, the subject exhibits a post-administration UPCR that is reduced by at least 50% compared to a baseline UPCR obtained from the subject prior to administering the FcRn antagonist, and if the baseline UPCR is greater than 3 mg / mg, the post-administration UPCR is less than 3 mg / mg.

65. 65. The method of any one of claims 62-64, wherein the post-administration UPCR is measured 24 or 52 weeks after administering the FcRn antagonist to the subject.

66. 66. The method of any one of claims 1-65, wherein, after administering the FcRn antagonist to the subject, the subject exhibits a reduced post-administration Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K score compared to a baseline SLEDAI-2K score obtained from the subject prior to administration of the FcRn antagonist.

67. 67. The method of claim 66, wherein the post-administration SLEDAI-2K score is measured 24 or 52 weeks after administering the FcRn antagonist to the subject.

68. 68. The method of any one of claims 1-67, wherein, after administering the FcRn antagonist to the subject, the subject exhibits a post-administration level of serum autoantibodies that is reduced compared to a baseline level of serum autoantibodies obtained from the subject prior to administration of the FcRn antagonist.

69. 69. The method of claim 68, wherein the post-administration level of the serum autoantibody is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% compared to the baseline level of the serum autoantibody obtained from the subject prior to administration of the FcRn antagonist.

70. 70. The method of claim 68 or 69, wherein the post-administration level of the serum autoantibody is measured 24 or 52 weeks after administering the FcRn antagonist to the subject.

71. 71. The method of any one of claims 68 to 70, wherein the serum autoantibody is selected from the group consisting of anti-dsDNA, ANA, aCL, anti-Sm, and anti-C1q.

72. 72. The method of any one of claims 1-71, wherein, after administering the FcRn antagonist to the subject, the subject exhibits a post-administration level of serum complement that is reduced compared to a baseline level of serum complement obtained from the subject prior to administration of the FcRn antagonist.

73. 73. The method of claim 72, wherein the post-administration level of serum complement is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% compared to the baseline level of serum complement obtained from the subject prior to administration of the FcRn antagonist.

74. 74. The method of claim 72 or 73, wherein the post-administration level of serum complement is measured 24 or 52 weeks after administering the FcRn antagonist to the subject.

75. 75. The method of any one of claims 72 to 74, wherein the serum complement is selected from the group consisting of C3, C4, CH50, and C1q-associated circulating immune complexes.

76. 76. The method of any one of claims 1 to 75, wherein, after administering the FcRn antagonist to the subject, the subject exhibits a post-administration level of serum IgG that is reduced compared to a baseline level of serum IgG obtained from the subject prior to administration of the FcRn antagonist.

77. 77. The method of claim 76, wherein the post-administration level of serum IgG is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% compared to the baseline level of serum IgG obtained from the subject prior to administration of the FcRn antagonist.

78. 78. The method of claim 76 or 77, wherein the post-administration level of serum IgG is measured 24 or 52 weeks after administering the FcRn antagonist to the subject.

79. 79. The method of any one of claims 1-78, wherein, after administering the FcRn antagonist to the subject, the subject exhibits a post-administration level of serum albumin that is not reduced compared to a baseline level of serum albumin obtained from the subject prior to administration of the FcRn antagonist.

80. 10. The method of any one of the preceding claims, wherein the FcRn antagonist is in an aqueous solution comprising about 4 mM sodium phosphate, about 146 mM sodium chloride, about 24 mM L-arginine, and about 0.0032% (w / v) polysorbate 80, and wherein the composition has a pH of about 6.

7.

81. 81. The method of claim 80, wherein the aqueous solution comprises about 3.2 mg / ml of the FcRn antagonist.

82. 80. The method of any one of claims 1-79, wherein the FcRn antagonist is in an aqueous solution comprising about 20 mM L-histidine, about 100 mM sodium chloride, about 60 mM sucrose, about 10 mM L-methionine, and about 0.04% (w / v) polysorbate 20, and wherein the composition has a pH of about 6.

0.

83. 83. The method of claim 82, wherein the aqueous solution comprises about 180 mg / ml of the FcRn antagonist.

84. 80. The method of any one of claims 1-79, wherein the FcRn antagonist is in an aqueous solution comprising about 20 mM L-histidine, about 50 mM L-arginine, about 100 mM sodium chloride, about 60 mM sucrose, about 10 mM L-methionine, and about 0.04% (w / v) polysorbate 80, and wherein the composition has a pH of about 6.

0.

85. 85. The method of claim 84, wherein the aqueous solution comprises about 200 mg / ml of the FcRn antagonist.

86. 86. An FcRn antagonist for use in the treatment of lupus nephritis, wherein said treatment is carried out by the method of any one of claims 1 to 85.

87. 86. An FcRn antagonist for use in the manufacture of a medicament for the treatment of lupus nephritis, wherein said treatment is carried out by the method of any one of claims 1 to 85.

88. 86. Use of an FcRn antagonist for the treatment of lupus nephritis by the method according to any one of claims 1 to 85.

89. 86. Use of an FcRn antagonist for the manufacture of a medicament for the treatment of lupus nephritis, wherein said treatment is carried out by the method of any one of claims 1 to 85.

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