Methods for treating lupus nephritis using FCRN antagonists

Abstract

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

Description

[0001] Related Applications

[0002] This application claims the benefit of priority of U.S. Provisional Patent Application Serial No. 63 / 382,566, filed Nov. 7, 2022, the entire disclosure of each of which is hereby incorporated by reference herein.

[0003] Reference to the Sequence Listing

[0004] This application contains a Sequence Listing which has been submitted electronically in accordance with the provisions of 37 C.F.R. § 1.821(e) and 1.825, and is hereby incorporated by reference in its entirety (the copy of the ST.26 created on Nov. 6, 2023, named “205806_SL.xml” and having a size of 40,649 bytes). Technical Field

[0005] The present disclosure relates to methods of treating lupus nephritis (LN). These methods involve using an antagonist of the human neonatal Fc receptor (FcRn), which antagonist is efgartigimod in certain embodiments. Background Art

[0006] It is estimated that over 2.5% of the 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 kidneys caused by SLE and is the most common life-threatening manifestation of SLE.

[0007] Among unselected SLE patients, approximately 25% to 50% have signs or symptoms of kidney disease at the time of SLE onset, and during the course of the disease, approximately 40% to 60% of SLE patients will develop kidney damage. In China, approximately half of SLE patients have kidney damage.

[0008] In active proliferative LN, induction therapy with mycophenolate mofetil (MMF) or mycophenolic acid (MPA) or low-dose intravenous (IV) cyclophosphamide (CYC) is recommended, all in combination with glucocorticoids. Alternative regimens include treatment with MMF and a calcineurin inhibitor (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 LN patients will develop end-stage renal disease (ESRD), which is the ultimate manifestation of LN. In addition, up to 60% of patients are unable to achieve treatment goals with currently available treatment options.

[0009] Therefore, there is a need in the art for improved treatment options for LN.

[0010] Therapeutic antagonism of FcRn has been investigated as a strategy for treating IgG-mediated autoimmune diseases such as generalized myasthenia gravis (gMG), immune thrombocytopenia (ITP), and pemphigus (pemphigus vulgaris (PV) and pemphigus foliaceus (PF)). FcRn is a major histocompatibility complex class I-like molecule involved in the recycling of immunoglobulin G (IgG) and thus responsible for the long IgG half-life. The significant clinical efficacy of FcRn antagonism appears to be directly related to the early removal of pathogenic IgG autoantibodies from the circulation.

[0011] Pathogenic autoantibodies and complement deposits are closely associated with the pathogenesis of SLE, particularly LN, where renal deposition of immune complexes is a hallmark of the disease. By reducing the pathogenic autoantibodies accumulated in the renal glomeruli, FcRn antagonists can provide a safer and more effective treatment option for LN patients. SUMMARY OF THE INVENTION

[0012] The present disclosure broadly relates to methods for treating lupus nephritis with FcRn antagonists.

[0013] The present disclosure provides a method for treating lupus nephritis in a subject in need thereof, the method 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 an FcRn-binding fragment thereof binds to FcRn with a higher affinity at pH 6.0 compared to the corresponding wild-type Fc region. In some embodiments, the variant Fc region or an FcRn-binding fragment thereof binds to FcRn with a higher affinity at pH 7.4 compared to the corresponding wild-type Fc region.

[0014] 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 a heterodimer. In some embodiments, the first Fc domain and / or the second Fc domain comprises the amino acids Y, T, E, K, and F located at EU positions 252, 254, 256, 433, and 434, respectively. In some embodiments, the first Fc domain and / or the second Fc domain comprises the amino acids Y, T, E, K, F, and Y located at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0015] 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.

[0016] In some embodiments, the FcRn antagonist is an anti-FcRn antibody.

[0017] 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 once a week or once every two weeks at a dose of 10 mg / kg to 30 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week at a dose of 10 mg / kg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week, once every two weeks, once every three weeks, once every four weeks, or once a month at a fixed dose of 750 mg to 3000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week or once every two weeks at a fixed dose of 1000 mg or 2000 mg.

[0018] 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.

[0019] In some embodiments, the method further comprises 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.

[0020] In some embodiments, the glucocorticoid is methylprednisolone. In some embodiments, methylprednisolone is administered intravenously once a day at a dose of 250 mg to 500 mg. In some embodiments, methylprednisolone is administered for 1 to 3 days per day. In some embodiments, methylprednisolone is administered for 3 days.

[0021] 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 gradually reduced to a dose of 7.5 mg / day within 12 weeks.

[0022] In some embodiments, MMF or MPA is administered daily. In some embodiments, MMF or MPA is administered at a daily dose, wherein the daily dose is gradually increased in divided doses to 1.5 g / day to 2 g / day within 4 weeks.

[0023] 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.

[0024] In some embodiments, the B lymphocyte targeting agent is selected from the group consisting of belimumab, rituximab, and obinutuzumab.

[0025] The present disclosure also provides a method of treating a subject in need thereof for lupus nephritis, the method 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 further comprises administering to the subject an effective amount of a glucocorticoid.

[0026] In some embodiments, the induction therapy further comprises administering to the subject an effective amount of methylprednisolone. In some embodiments, methylprednisolone is intravenously administered once a day at a dose of 250 mg to 500 mg. In some embodiments, methylprednisolone is administered daily for 1 to 3 days. In some embodiments, methylprednisolone is administered for 3 days.

[0027] In some embodiments, the induction therapy comprises administering prednisone to the subject. 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 gradually reduced to a dose of 7.5 mg / day within 12 weeks.

[0028] In some embodiments, the induction therapy further comprises administering to the subject an effective amount of a daily dose of MMF or MPA. In some embodiments, the daily dose of MMF or MPA is gradually increased in divided doses to 1.5 g / day to 2 g / day within 4 weeks.

[0029] In some embodiments, the induction therapy further comprises administering to the subject a dose of an effective amount of hydroxychloroquine. In some embodiments, the dose of hydroxychloroquine is up to 5 mg / kg / day. In some embodiments, hydroxychloroquine is administered for 24 weeks. In some embodiments, the dose of hydroxychloroquine is administered for at least 24 weeks.

[0030] In some embodiments, the induction therapy further comprises administering to the subject an effective amount of a B lymphocyte targeting agent. In some embodiments, the B lymphocyte targeting agent is selected from the group consisting of belimumab, rituximab, and obinutuzumab.

[0031] In some embodiments, after administering an FcRn antagonist to the subject, the subject exhibits an estimated glomerular filtration rate (eGFR) of at least 60 mL / min / 1.73m 2 of post - administration eGFR. In some embodiments, after administering an FcRn antagonist to the subject, the subject exhibits a post - administration eGFR that is less than 20% lower than the baseline eGFR obtained from the subject prior to administering the FcRn antagonist. In some embodiments, the post - administration eGFR is measured at 24 or 52 weeks after administering the FcRn antagonist to the subject. In some embodiments, after administering an FcRn antagonist to the subject, the subject exhibits a post - administration eGFR of at least 90 mL / min / 1.73m 2 of post - administration eGFR. In some embodiments, after administering an FcRn antagonist to the subject, the subject exhibits a post - administration eGFR that is less than 10% lower than the baseline eGFR obtained from the subject prior to administering the FcRn antagonist. In some embodiments, the post - administration eGFR is measured at 24 or 52 weeks after administering the FcRn antagonist to the subject.

[0032] In some embodiments, after administering an 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 an FcRn antagonist to the subject, the subject exhibits a post - administration UPCR that is at least 50% lower than the baseline UPCR obtained from the subject prior to administering the FcRn antagonist, and wherein if the baseline UPCR is at most 3 mg / mg, then the post - administration UPCR is less than 1 mg / mg. In some embodiments, after administering an FcRn antagonist to the subject, the subject exhibits a post - administration UPCR that is at least 50% lower than the baseline UPCR obtained from the subject prior to administering the FcRn antagonist, and wherein if the baseline UPCR is greater than 3 mg / mg, then the post - administration UPCR is less than 3 mg / mg. In some embodiments, the post - administration UPCR is measured at 24 or 52 weeks after administering the FcRn antagonist to the subject.

[0033] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post - administration Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) - 2K score that is reduced compared to the baseline SLEDAI - 2K score obtained from the subject prior to administering the FcRn antagonist. In some embodiments, the post - administration SLEDAI - 2K score is measured at 24 or 52 weeks after administering the FcRn antagonist to the subject.

[0034] 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 prior to 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 prior to administering the FcRn antagonist. In some embodiments, the post - administration level of serum autoantibodies is measured at 24 or 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.

[0035] 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 prior to 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 the baseline level of serum complement obtained from the subject prior to administering the FcRn antagonist. In some embodiments, the post - administration level of serum complement is measured at 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 - binding circulating immune complexes.

[0036] 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 prior to 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 prior to administering the FcRn antagonist. In some embodiments, the post - administration level of serum IgG is measured at 24 or 52 weeks after administering the FcRn antagonist to the subject.

[0037] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post - administration level of serum albumin that is not decreased compared to the baseline level of serum albumin obtained from the subject prior to administering the FcRn antagonist.

[0038] 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, wherein 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.

[0039] 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, wherein the composition has a pH of about 6.0. In some embodiments, the aqueous solution comprises about 180 mg / ml of the FcRn antagonist.

[0040] 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, wherein the composition has a pH of about 6.0. In some embodiments, the aqueous solution comprises about 200 mg / ml of the FcRn antagonist.

[0041] The present disclosure also provides an FcRn antagonist for use in treating lupus nephritis, wherein the treatment is carried out according to the methods described above and herein.

[0042] The present disclosure also provides an FcRn antagonist for use in manufacturing a medicament for treating lupus nephritis, wherein the treatment is carried out according to the methods described above and herein.

[0043] The present disclosure also provides the use of an FcRn antagonist for treating lupus nephritis according to the methods described above and herein.

[0044] The present disclosure also provides the use of an FcRn antagonist for manufacturing a medicament for treating lupus nephritis, wherein the treatment is carried out according to the methods described above and herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1A set of graphs showing the levels of IgG circulating immune complexes (IgG CIC) (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 represents the median. The dashed line represents CS (clinical significance). PDAI: Pemphigus disease area index; CR: Complete clinical remission; EoT: End of treatment; EoS: End of study. The data show that efgartigimod reduces the level of circulating immune complexes. Detailed Description

[0046] The present disclosure provides engineered FcRn antagonists and methods for their use in treating LN. Advantageously, the methods disclosed herein allow for long-term preservation of kidney function, prevention of disease exacerbation, prevention of organ damage, management of complications, improvement in patient survival, and improvement in quality of life associated with the disease.

[0047] Definitions

[0048] As used herein, the term "FcRn" refers to the neonatal Fc receptor. Exemplary FcRn molecules include the 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.

[0049] As used herein, the term "FcRn antagonist" refers to any agent that specifically binds to FcRn and inhibits the binding of immunoglobulins 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 through the Fc region and inhibits the binding of immunoglobulins 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 an antigen-binding site. In one embodiment, the term "FcRn antagonist" refers to an antibody or an antigen-binding fragment thereof that specifically binds to FcRn via its antigen-binding domain or via its Fc region and inhibits the binding of the Fc region of an immunoglobulin (e.g., an IgG autoantibody) to FcRn.

[0050] As used herein, the terms "antibody" and "antibodies" include full-length antibodies, antigen-binding fragments of full-length antibodies, and molecules comprising antibody CDRs, VH regions, or VL regions. 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 chains 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, intracellular antibodies, heteroconjugate antibodies, antibody-drug conjugates, single domain antibodies (sdAbs), monovalent antibodies, single chain antibodies or single chain Fvs (scFvs), camelid antibodies, affinity antibody 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 foregoing. An antibody can be of 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 ).

[0051] 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 the antibody. In some embodiments, the Fc domain comprises at least a portion of the hinge region (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.

[0052] As used herein, the term "hinge region" refers to the portion of the heavy chain molecule that joins 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, thus allowing the two N-terminal antigen-binding regions to move independently. In some embodiments, the hinge region comprises approximately 11 to 17 amino acid residues and is flexible, thus 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: upper, middle, and lower hinge domains. The FcRn antagonists of the present disclosure can include all or any part of the hinge region. In some embodiments, the hinge region is from an IgG1 antibody. In some embodiments, the hinge region comprises the amino acid sequence EPKSCDKTHTCPPCP (SEQ ID NO:12).

[0053] 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. The native Fc region is homodimeric. The Fc region can be derived from any native immunoglobulin. In some embodiments, it is formed by the IgA, IgD, IgE, or IgG heavy chain constant region. In some embodiments, the Fc region is formed by the 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 by the IgG1 heavy chain constant region. In some embodiments, the IgG1 heavy chain constant region comprises the allotypes G1m1(a), G1m2(x), G1m3(f), or G1m17(z). 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 herein by reference in their entireties.

[0054] As used herein, the term "variant Fc region" refers to an Fc region that has one or more alterations relative to the native Fc region. Alterations can include amino acid substitutions, additions, and / or deletions, the attachment of additional moieties, and / or alterations of native glycans. The term encompasses heterodimeric Fc regions in which each of the constitutive Fc domains is different. The term also encompasses single-chain Fc regions in which the constitutive Fc domains are joined together by a linker moiety.

[0055] As used herein, the term "FcRn-binding fragment" refers to a portion of the Fc region that is sufficient to confer FcRn binding.

[0056] As used herein, the term "EU position" refers to the amino acid positions in the EU numbering convention of the Fc region as described by Edelman, G.M. et al., Proc. Natl. Acad. USA, 63, 78 - 85 (1969) and by Rabat et al. in "Sequences of Proteins of Immunological Interest," U.S. Dept. Health and Human Services, 5th ed., 1991.

[0057] As used herein, the term "baseline" refers to a measurement (e.g., frequency of B cells, IgG level) in a patient (e.g., in the patient's blood or urine) prior to the first administration (e.g., intravenous or subcutaneous administration) of a treatment (e.g., an FcRn antagonist).

[0058] As used herein, the term "autoantibody - mediated disease" refers to any disease or disorder in which the underlying pathology is at least in part caused by pathogenic IgG autoantibodies.

[0059] As used herein, the term "treat" ("treat", "treating", and "treatment") refers to the therapeutic or prophylactic measures described herein. A "treatment" method involves administering a polypeptide to a subject having a disease or disorder or susceptible to such a disease or disorder to prevent, cure, delay the disease or disorder or a recurrent disease or disorder, reduce its severity or improve one or more of its symptoms, or to extend the subject's survival period beyond that expected in the absence of such treatment.

[0060] As used herein, the term "effective amount" in the context of administering a therapy to a subject refers to the amount of the therapy that achieves the desired prophylactic or therapeutic effect.

[0061] As used herein, the term "dose" or "dosage" refers to the amount of an agent administered to a subject in a single administration.

[0062] As used herein, the terms "fixed dose" or "uniform dose" both refer to not being based on the characteristics of the subject (e.g., weight, e.g., within a set range; gender; age, e.g., within a set range; etc.).

[0063] As used herein, the term "remission" refers to a patient who has no novel markers of the autoantibody - mediated disease and in whom the baseline markers of the disease have completely regressed or healed.

[0064] As used herein, the terms "relapse" or "flare" refer to the appearance of physical symptoms and / or an increase in markers of an autoantibody-mediated disease in a patient with an autoantibody-mediated disease after a remission period of the autoantibody-mediated disease. In some embodiments, the flare is a lupus nephritis (LN) flare. In some embodiments, an LN flare is characterized by a 20% increase in the urine protein creatinine ratio (UPCR) compared to baseline. In some embodiments, the flare is an extrarenal SLE flare. In some embodiments, an extrarenal SLE flare is characterized by an increase in the SLEDAI-2K score that is not caused by hypocomplementemia, an increase in the level of anti-dsDNA antibodies, the initiation of a new immunosuppressive therapy, or an increase in corticosteroids.

[0065] As used herein, the terms "subject" or "patient" or "participant" include 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 a human. In one embodiment, the human subject or patient or participant is Asian.

[0066] As used herein, when referring to a measurable value, such as a dose, the terms "about" or "approximately" encompass variations of ±20%, ±15%, ±10%, ±5%, ±1% or ±0.1% of a given value or range, so long as it is suitable to carry out the methods disclosed herein.

[0067] Lupus nephritis

[0068] Systemic lupus erythematosus (SLE) is a chronic disease that is both complex and challenging to diagnose and treat. It is a heterogeneous autoimmune disease characterized by dysregulation of T and B lineage cells and other components of the innate immune system. The hallmark of the disease is the production of pathogenic autoantibodies against double-stranded DNA (dsDNA), phospholipids, blood cells, and other targets.

[0069] SLE manifestations are associated with multiple autoantibodies, the subsequent formation and deposition of immune complexes, and other immune processes. LN is an inflammatory autoimmune disease of the kidney caused by SLE and is the most common life-threatening manifestation of systemic lupus. It is mainly caused by type 3 hypersensitivity reactions, in which anti-double-stranded DNA (anti-dsDNA) binds to DNA, and the DNA forms anti-dsDNA immune complexes. These immune complexes deposit in the subepithelial and / or epithelial spaces of the glomerular basement membrane of the kidney near the glomerular membrane. This leads to an inflammatory response during the onset of LN, in which the complement pathway is activated, leading to the influx of neutrophils and other inflammatory cells. At any time during the course of the SLE disease, approximately 40% to 60% of SLE patients will develop kidney damage, with a high incidence or mortality rate. Approximately 25-50% of SLE patients already have signs or symptoms of kidney disease at the time of SLE diagnosis. In China, approximately half of SLE patients have kidney damage.

[0070] All LN patients are considered to have chronic kidney disease (CKD), which progresses to end-stage renal disease (ESRD) in a subset of LN patients. In China, LN is one of the most common causes of ESRD. Symptoms of LN include blood in the urine, foamy urine, proteinuria, high blood pressure, water pressure, joint pain, muscle pain, muscle aches, malarial rash, and high levels of creatinine in the blood.

[0071] LN is histologically divided into 6 different categories, which represent different manifestations and severities of kidney damage in SLE. The rationale for classifying LN into different categories also takes into account differences in prognosis. Glomerulonephritis is the most common form of kidney disease in SLE but is often accompanied by tubulointerstitial and vascular lesions. Usually, LN with class VI represents kidney atrophy in ESRD. Patients with proliferative LN with different degrees (class III, IV, or V) rather than class I or II LN are at risk of immediate progression of CKD. These categories are the most severe manifestations of kidney pathology, and they require aggressive immunosuppressive therapy to prevent progression to ESRD and to minimize the associated morbidity and mortality.

[0072] The goals of treatment include patient survival, long-term preservation of kidney function, prevention of disease exacerbation, prevention of organ damage, management of comorbidities, and improvement of disease-related quality of life. In the recommendations of the European League Against Rheumatism and the European Renal Association-European Dialysis and Transplant Association (EULAR / ERA-EDTA), in active proliferative LN, initial (induction) treatment is with mycophenolate mofetil (MMF, 2 g to 3 g / day or an equivalent dose of mycophenolic acid [MPA]) or low-dose intravenous (IV) cyclophosphamide (CYC; 500 mg × 6 bi-weekly doses), both recommended in combination with glucocorticoids (pulse of IV methylprednisolone followed by oral prednisone). The MMF / calcineurin inhibitor (CNI) (especially tacrolimus) combination and high-dose CYC are alternative approaches for patients with renal-range proteinuria and poor prognostic factors. Long-term maintenance treatment should then be with MMF or azathioprine, with no or low-dose (<7.5 mg / day) glucocorticoids. Similarly, in the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines, for patients with active LN, initial treatment includes corticosteroids (IV methylprednisolone 0.25 - 0.5 g / day for 1 to 3 days followed by oral prednisone 0.6 - 1 mg / kg / day [not to exceed 80 mg / day] and tapered to maintenance dose over several months) and calcineurin inhibitors (e.g., tacrolimus and voclosporin), mycophenolic acid analogs (e.g., MMF or sodium mycophenolate), 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 biologic agents, such as but not limited to, belimumab and rituximab.

[0073] Despite aggressive immunosuppressive therapy, in patients with LN, 10% to 30% of patients will still develop ESRD. Although these prognoses have improved over the past 30 years, the risk of treatment failure still exists (defined as death, ESRD, persistent doubling of serum creatinine, LN exacerbation, or need for rescue medications). There is clearly a need for more effective treatment as up to 60% of patients are unable to achieve the treatment targets of current treatment options.

[0074] A large body of evidence shows that early reduction of proteinuria, especially within 6 to 12 months from the start of treatment, is the best predictor of improved long-term outcomes, including reduced risk of disease exacerbation, ESRD, and death. Thus, proteinuria or UPCR is a useful parameter for assessing treatment efficacy and is the preferred prognostic indicator of regulatory agencies. Early reduction of UPCR indicates long-term benefit of LN treatment.

[0075] FcRn antagonist

[0076] 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.

[0077] In some embodiments, the FcRn antagonists disclosed herein comprise two, three, or four FcRn binding regions, such as Fc regions.

[0078] Any Fc region can be modified to produce variant Fc regions for use in the methods disclosed herein. Generally, the Fc region or its FcRn binding fragment is from a human immunoglobulin. However, it should be understood that the Fc region can be derived from immunoglobulins of any other mammalian species, including, for example, camelid species, rodents (e.g., mice, rats, rabbits, guinea pigs), or non-human primate (e.g., orangutan, macaque) species. Additionally, the Fc region or portions 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 set forth in US2011 / 0243966A1, which is incorporated herein by reference in its entirety. A variety of Fc region gene sequences (e.g., human constant region gene sequences) are available in publicly available depositories.

[0079] The Fc region can be further truncated or internally deleted to produce its minimal FcRn binding fragment. The ability of the Fc region fragment to bind to FcRn can be determined using any binding assay recognized in the art (e.g., ELISA).

[0080] To enhance the manufacturability of the FcRn antagonists disclosed herein, preferably, the native Fc region does not contain any non-disulfide-linked cysteine residues. Thus, in one embodiment, the Fc region does not contain free cysteine residues.

[0081] 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 alterations, substitutions, insertions, and / or deletions that confer the desired characteristics. In some embodiments, the FcRn antagonist comprises a variant Fc region or FcRn-binding fragment thereof that binds to FcRn with higher affinity at pH 5.5 compared to the corresponding wild-type Fc region. In one embodiment, the FcRn antagonist comprises, consists of, or consists essentially of a variant Fc region or 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 FcRn-binding fragment thereof that binds to FcRn with higher affinity at both acidic and neutral pHs.

[0082] 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, IgG is IgG1, IgG2, IgG3, or IgG4. In some embodiments, human IgG is human IgG1, human IgG2, human IgG3, or human IgG4. In some embodiments, the variant Fc region is different from the human IgG1 Fc region. In some embodiments, the human IgG1 Fc region comprises the allotypes G1m1(a), G1m2(x), G1m3(f), or G1m17(z).

[0083] In one embodiment, the variant Fc region or FcRn-binding fragment thereof consists of two Fc domains.

[0084] 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 the amino acids Y, T, E, K, and F located at EU positions 252, 254, 256, 433, and 434, respectively. In one embodiment, the first Fc domain and / or the second Fc domain comprises the amino acids Y, T, E, K, F, and Y located at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0085] In some embodiments, the FcRn antagonists disclosed herein comprise or consist of at least one Fc domain, wherein the amino acid sequence of the at least one Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:13 provided in Table 1 below.

[0086] Table 1

[0087]

[0088] In some embodiments, the FcRn antagonists disclosed herein comprise or consist of a variant Fc region, which comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain comprise or consist of the amino acid sequence of SEQ ID NO:13.

[0089] In some embodiments, the FcRn antagonists disclosed herein 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 a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain independently comprise or consist of an amino acid sequence selected from the group consisting of: SEQ ID NO:1-3 and 14-31. In some embodiments, the dimer is a heterodimer or a homodimer.

[0090] Table 2

[0091]

[0092]

[0093]

[0094]

[0095] In one embodiment, the first Fc domain and / or the second Fc domain independently comprise an amino acid sequence 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 independently comprise an amino acid sequence selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3.

[0096] In one embodiment, the first Fc domain and / or the second Fc domain comprises an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, 2, 3, and 30. In one embodiment, the first Fc domain and the second Fc domain each comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, 2, 3, and 30.

[0097] In some embodiments, the FcRn antagonist comprises a population of FcRn antagonist molecules. In some embodiments, the FcRn antagonist comprising the first Fc domain and the second Fc domain is the major FcRn antagonist molecule in the population of FcRn antagonist molecules, and the first Fc domain and the second Fc domain each comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, 2, and 3. In some embodiments, the FcRn antagonist comprising the first Fc domain and the second Fc domain is the major FcRn antagonist molecule in the population of FcRn antagonist molecules, and the first Fc domain and the second Fc domain each comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, 2, 3, and 30. In some embodiments, the major FcRn antagonist molecule accounts for at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the population of FcRn antagonist molecules.

[0098] 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.

[0099] In one embodiment, the FcRn antagonist consists of a variant Fc region, wherein the variant Fc region comprises two Fc domains, and 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, 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 and SEQ ID NO:30.

[0100] In certain embodiments, the variant Fc region is a heterodimer, wherein the constituent Fc domains are different from each other. Methods for generating Fc heterodimers are known in the art (see, for example, US 8,216,805, which is 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 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 comprises or consists of a variant Fc region, wherein the variant Fc region comprises or consists of two Fc domains that form a heterodimer, wherein the amino acid sequence of the first Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:1, and the amino acid sequence of the second Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:3. In one embodiment, the FcRn antagonist comprises or consists of a variant Fc region, wherein the variant Fc region comprises or consists of two Fc domains that form a heterodimer, wherein the amino acid sequence of the first Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:2, and the amino acid sequence of the second Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:3. In one embodiment, the FcRn antagonist comprises or consists of a variant Fc region, wherein the variant Fc region comprises or consists of two Fc domains that form a heterodimer, wherein the amino acid sequence of the first Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:3, and the amino acid sequence of the second Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2.

[0101] In one embodiment, the FcRn antagonist consists of a variant Fc region, wherein the variant Fc region consists of two Fc domains forming 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 comprises or consists of a variant Fc region, wherein the variant Fc region comprises or consists of two Fc domains forming a heterodimer, wherein the amino acid sequence of the first Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:1, and the amino acid sequence of the second Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:2, SEQ ID NO:3 or SEQ ID NO:30. In one embodiment, the FcRn antagonist comprises or consists of a variant Fc region, wherein the variant Fc region comprises or consists of two Fc domains forming a heterodimer, wherein the amino acid sequence of the first Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:2, and the amino acid sequence of the second Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:3 or SEQ ID NO:30. In one embodiment, the FcRn antagonist comprises or consists of a variant Fc region, wherein the variant Fc region comprises or consists of two Fc domains forming a heterodimer, wherein the amino acid sequence of the first Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:3, and the amino acid sequence of the second Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2 or SEQ ID NO:30. In one embodiment, the FcRn antagonist comprises or consists of a variant Fc region, wherein the variant Fc region comprises or consists of two Fc domains forming a heterodimer, wherein the amino acid sequence of the first Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:30, and the amino acid sequence of the second Fc domain comprises or consists of the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2 or SEQ ID NO:3.

[0102] In one embodiment, the FcRn antagonist comprises or consists of a variant Fc region, wherein the variant Fc region comprises or consists of two Fc domains forming a homodimer, and the amino acid sequence of each of the Fc domains comprises or consists of the amino acid sequence of SEQ ID NO:1.

[0103] In one embodiment, the FcRn antagonist comprises or consists of a variant Fc region, wherein the variant Fc region comprises or consists of two Fc domains that form a homodimer, and wherein the amino acid sequence of each of the Fc domains comprises or consists of the amino acid sequence of SEQ ID NO:2.

[0104] In one embodiment, the FcRn antagonist comprises or consists of a variant Fc region, wherein the variant Fc region comprises or consists of two Fc domains that form a homodimer, and wherein the amino acid sequence of each of the Fc domains comprises or consists of the amino acid sequence of SEQ ID NO:3.

[0105] In one embodiment, the FcRn antagonist comprises or consists of a variant Fc region, wherein the variant Fc region comprises or consists of two Fc domains that form a homodimer, and wherein the amino acid sequence of each of the Fc domains comprises or consists of the amino acid sequence of SEQ ID NO:30.

[0106] In some embodiments, the FcRn antagonist comprises glycosylation on one or both of the Fc domains. In some embodiments, the FcRn antagonist molecule comprises glycosylation at EU position 297 on one or both of the Fc domains. In some embodiments, the glycosylation 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.

[0107] 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 comprises 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 comprises fucose.

[0108] In some embodiments, the FcRn antagonist lacks an amino acid at EU position 441 of one or both of the Fc domains. In some embodiments, the FcRn antagonist comprises glycine and lysine at EU positions 440 and 441, respectively. In some embodiments, the FcRn antagonist lacks an amino acid at EU positions 440 and 441. In some embodiments, the FcRn antagonist comprises amidated proline at EU position 439. In some embodiments, the FcRn antagonist lacks an amino acid at EU positions 440 and 441 and comprises amidated proline at EU position 439.

[0109] 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 at EU positions 225 and 226, respectively. In some embodiments, the FcRn antagonist lacks amino acids at EU positions 221, 222, 223, 224, 225, and 226.

[0110] 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 a plurality of subsets of FcRn antagonist molecules. In some embodiments, the population of FcRn antagonist molecules comprises, consists of, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 subsets. In some embodiments, the population of FcRn antagonist molecules comprises, consists of, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 subsets.

[0111] In some embodiments, the first subset of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first Fc domain and the second Fc domain comprises 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.

[0112] In some embodiments, a second subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain comprise or consist of amino acid sequences that are at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequences of SEQ ID NO: 3 and 22, respectively.

[0113] In some embodiments, a third subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain comprise or consist of amino acid sequences that are at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequences of SEQ ID NO: 3 and 19, respectively.

[0114] In some embodiments, a fourth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first Fc domain and the second Fc domain 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 subgroup are deaminated.

[0115] In some embodiments, a fifth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain respectively comprise or consist of amino acid sequences that are at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequences of SEQ ID NO: 3 and 19, respectively, and wherein one asparagine residue in each FcRn antagonist molecule in the fifth subgroup is deaminated.

[0116] In some embodiments, the sixth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain comprise or consist of amino acid sequences that are at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequences of SEQ ID NO:2 and 3, respectively.

[0117] In some embodiments, the seventh subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain each 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 NO:2 and 3, respectively, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the seventh subgroup is oxidized.

[0118] In some embodiments, the eighth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first Fc domain and the second Fc domain 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:2.

[0119] In some embodiments, the ninth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain comprise or consist of amino acid sequences that are at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequences of SEQ ID NO:3 and 16, respectively.

[0120] In some embodiments, the tenth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain each 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 NO:2 and 3, respectively, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the tenth subgroup is oxidized.

[0121] In some embodiments, the eleventh subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first Fc domain and the second Fc domain each 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 subgroup is oxidized.

[0122] In some embodiments, the first subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first Fc domain and the second Fc domain each comprise or consist of the amino acid sequence of SEQ ID NO:3.

[0123] In some embodiments, the second subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain each comprise or consist of the amino acid sequences of SEQ ID NO:3 and 22, respectively.

[0124] In some embodiments, the third subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain each comprise or consist of the amino acid sequences of SEQ ID NO:3 and 19, respectively.

[0125] In some embodiments, a fourth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first Fc domain and the second Fc domain comprise or consist of the amino acid sequence of SEQ ID NO:3, and wherein two asparagine residues in each FcRn antagonist molecule in the fourth subgroup are deaminated.

[0126] In some embodiments, a fifth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain respectively comprise or consist of the amino acid sequences of SEQ ID NO:3 and 19, and wherein one asparagine residue in each FcRn antagonist molecule in the fifth subgroup is deaminated.

[0127] In some embodiments, a sixth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain respectively comprise or consist of the amino acid sequences of SEQ ID NO:2 and 3.

[0128] In some embodiments, a seventh subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain respectively comprise or consist of the amino acid sequences of SEQ ID NO:2 and 3, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the fourth subgroup is oxidized.

[0129] In some embodiments, an eighth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first Fc domain and the second Fc domain comprise or consist of the amino acid sequence of SEQ ID NO:2.

[0130] In some embodiments, a ninth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain respectively comprise or consist of the amino acid sequences of SEQ ID NO:3 and 16.

[0131] In some embodiments, the tenth subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first Fc domain and the second Fc domain respectively comprise or consist of the amino acid sequences of SEQ ID NO: 2 and 3, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the tenth subgroup is oxidized.

[0132] In some embodiments, the eleventh subgroup of FcRn antagonist molecules comprises or consists of a variant Fc region that comprises or consists of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first Fc domain and the second Fc domain comprise or consist of 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 subgroup is oxidized.

[0133] In some embodiments, the population of FcRn antagonist molecules comprises a combination of or consists of a first subgroup and one of a second subgroup, a third subgroup, a fourth subgroup, a fifth subgroup, a sixth subgroup, a seventh subgroup, an eighth subgroup, a ninth subgroup, a tenth subgroup, or an eleventh subgroup. In some embodiments, the population of FcRn antagonist molecules comprises a combination of or consists of a first subgroup and two of a second subgroup, a third subgroup, a fourth subgroup, a fifth subgroup, a sixth subgroup, a seventh subgroup, an eighth subgroup, a ninth subgroup, a tenth subgroup, or an eleventh subgroup. In some embodiments, the population of FcRn antagonist molecules comprises a combination of or consists of a first subgroup and three of a second subgroup, a third subgroup, a fourth subgroup, a fifth subgroup, a sixth subgroup, a seventh subgroup, an eighth subgroup, a ninth subgroup, a tenth subgroup, or an eleventh subgroup. In some embodiments, the population of FcRn antagonist molecules comprises a combination of or consists of a first subgroup and four of a second subgroup, a third subgroup, a fourth subgroup, a fifth subgroup, a sixth subgroup, a seventh subgroup, an eighth subgroup, a ninth subgroup, a tenth subgroup, or an eleventh subgroup. In some embodiments, the population of FcRn antagonist molecules comprises a combination of or consists of a first subgroup and five of a second subgroup, a third subgroup, a fourth subgroup, a fifth subgroup, a sixth subgroup, a seventh subgroup, an eighth subgroup, a ninth subgroup, a tenth subgroup, or an eleventh subgroup. In some embodiments, the population of FcRn antagonist molecules comprises a combination of or consists of a first subgroup and six of a second subgroup, a third subgroup, a fourth subgroup, a fifth subgroup, a sixth subgroup, a seventh subgroup, an eighth subgroup, a ninth subgroup, a tenth subgroup, or an eleventh subgroup. In some embodiments, the population of FcRn antagonist molecules comprises a combination of or consists of a first subgroup and seven of a second subgroup, a third subgroup, a fourth subgroup, a fifth subgroup, a sixth subgroup, a seventh subgroup, an eighth subgroup, a ninth subgroup, a tenth subgroup, or an eleventh subgroup. In some embodiments, the population of FcRn antagonist molecules comprises a combination of or consists of a first subgroup and eight of a second subgroup, a third subgroup, a fourth subgroup, a fifth subgroup, a sixth subgroup, a seventh subgroup, an eighth subgroup, a ninth subgroup, a tenth subgroup, or an eleventh subgroup. In some embodiments, the population of FcRn antagonist molecules comprises a combination of or consists of a first subgroup and nine of a second subgroup, a third subgroup, a fourth subgroup, a fifth subgroup, a sixth subgroup, a seventh subgroup, an eighth subgroup, a ninth subgroup, a tenth subgroup, or an eleventh subgroup. In some embodiments, the population of FcRn antagonist molecules comprises a combination of or consists of a first subgroup and all of a second subgroup, a third subgroup, a fourth subgroup, a fifth subgroup, a sixth subgroup, a seventh subgroup, an eighth subgroup, a ninth subgroup, a tenth subgroup, or an eleventh subgroup.

[0134] In some embodiments, the population comprises or consists of a first subgroup and a second subgroup. In some embodiments, the population comprises or consists of a first subgroup and a third subgroup. In some embodiments, the population comprises or consists of a first subgroup and a fourth subgroup. In some embodiments, the population comprises or consists of a first subgroup and a fifth subgroup. In some embodiments, the population comprises or consists of a first subgroup and a sixth subgroup. In some embodiments, the population comprises or consists of a first subgroup and a seventh subgroup. In some embodiments, the population comprises or consists of a first subgroup and an eighth subgroup. In some embodiments, the population comprises or consists of a first subgroup and a ninth subgroup. In some embodiments, the population comprises or consists of a first subgroup and a tenth subgroup. In some embodiments, the population comprises or consists of a first subgroup and an eleventh subgroup. In some embodiments, the populations listed above further comprise or consist of 1, 2, 3, 4, 5, 6, 7, 8, or 9 additional subgroups. In some embodiments, these additional subgroups are one or more of the above-listed subgroups.

[0135] In some embodiments, the population comprises or consists of a first subgroup and a seventh subgroup, a ninth subgroup, or an eleventh subgroup. In some embodiments, the population comprises or consists of a first subgroup, a seventh subgroup, a ninth subgroup, and an eleventh subgroup.

[0136] In some embodiments, the first subgroup comprises 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 subgroup comprises 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 subgroup comprises 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% of the population of FcRn antagonist molecules. In some embodiments, the first subgroup comprises 40%-90%, 50%-80%, or 55%-70% of the population of FcRn antagonist molecules. In some embodiments, the first subgroup comprises 56.9%-68.3% or 59.5%-67.9% of the population of FcRn antagonist molecules.

[0137] 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 FcRn antagonist molecular population. 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 FcRn antagonist molecular population. In some embodiments, the second subpopulation comprises 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the FcRn antagonist molecular population. In some embodiments, the second subpopulation comprises 0.5%-3.0%, 1.0%-2.5%, or 1.0%-2.0% of the FcRn antagonist molecular population. In some embodiments, the second subpopulation comprises 0.8%-2.0% or 0.8%-2.1% of the FcRn antagonist molecular population.

[0138] In some embodiments, the third 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 FcRn antagonist molecular population. In some embodiments, the third subpopulation comprises about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1%, or about 0.5% of the FcRn antagonist molecular population. In some embodiments, the third subpopulation comprises 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the FcRn antagonist molecular population. In some embodiments, the third subpopulation comprises 0.5%-3.0%, 1.0%-2.5%, or 1.0%-2.0% of the FcRn antagonist molecular population. In some embodiments, the third subpopulation comprises 1.1%-2.1% or 1.0%-1.9% of the FcRn antagonist molecular population.

[0139] In some embodiments, the fourth subpopulation comprises less than 5%, less than 4%, less than 3%, less than 2%, or less than 1% of the FcRn antagonist molecular population. In some embodiments, the fourth subpopulation comprises about 5%, about 4%, about 3%, about 2%, or about 1% of the FcRn antagonist molecular population. In some embodiments, the fourth subpopulation comprises 5%, 4%, 3%, 2%, or 1% of the FcRn antagonist molecular population. In some embodiments, the fourth subpopulation comprises 1%-5%, 2%-4%, or 2%-3% of the FcRn antagonist molecular population. In some embodiments, the fourth subpopulation comprises 2.1%-3.2% or 2.0%-3.1% of the FcRn antagonist molecular population.

[0140] In some embodiments, the fifth subpopulation comprises 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 FcRn antagonist molecular population. In some embodiments, the fifth subpopulation comprises about 12%, about 11%, about 10%, about 9%, about 8%, about 7%, about 6%, or about 5% of the FcRn antagonist molecular population. In some embodiments, the fifth subpopulation comprises 12%, 11%, 10%, 9%, 8%, 7%, 6%, or 5% of the FcRn antagonist molecular population. In some embodiments, the fifth subpopulation comprises 5%-12%, 6%-10%, or 7%-8% of the FcRn antagonist molecular population. In some embodiments, the fifth subpopulation comprises 6.8%-9.4% or 6.9%-8.7% of the FcRn antagonist molecular population.

[0141] In some embodiments, the sixth subpopulation comprises 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 FcRn antagonist molecular population. In some embodiments, the sixth subpopulation comprises 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 FcRn antagonist molecular population. In some embodiments, the sixth subpopulation comprises 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, or 6% of the FcRn antagonist molecular population. In some embodiments, the sixth subpopulation comprises 7%-17%, 10%-15%, or 11%-12% of the FcRn antagonist molecular population. In some embodiments, the sixth subpopulation comprises 7.0%-14.0% or 10.0%-14.4% of the FcRn antagonist molecular population.

[0142] 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 FcRn antagonist molecular population. In 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 FcRn antagonist molecular population. 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 FcRn antagonist molecular population. In some embodiments, the seventh subpopulation comprises 0.5%-5.5%, 1.0%-3.0% or 1.5%-2.5% of the FcRn antagonist molecular population. In some embodiments, the seventh subpopulation comprises 1.5%-5.5% or 1.4%-4.9% of the FcRn antagonist molecular population.

[0143] 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 FcRn antagonist molecular population. In 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 FcRn antagonist molecular population. 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 FcRn antagonist molecular population. In some embodiments, the eighth subpopulation comprises 2.5%-7.5%, 3.0%-5.0% or 3.5%-4.5% of the FcRn antagonist molecular population. In some embodiments, the eighth subpopulation comprises 2.9%-7.4% or 3.0%-6.3% of the FcRn antagonist molecular population.

[0144] In some embodiments, the ninth subpopulation comprises 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 FcRn antagonist molecular population. In some embodiments, the ninth subpopulation comprises about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1%, or about 0.5% of the FcRn antagonist molecular population. In some embodiments, the ninth subpopulation comprises 3.5%, 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the FcRn antagonist molecular population. In some embodiments, the ninth subpopulation comprises 0.5%-3.5%, 1.5%-2.0%, or 1.0%-1.5% of the FcRn antagonist molecular population. In some embodiments, the ninth subpopulation comprises 0.4%-3.2% or 0.5%-2.6% of the FcRn antagonist molecular population.

[0145] 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 FcRn antagonist molecular population. In some embodiments, the tenth subpopulation comprises about 2.0%, about 1.5%, about 1%, or about 0.5% of the FcRn antagonist molecular population. In some embodiments, the tenth subpopulation comprises 2.0%, 1.5%, 1%, or 0.5% of the FcRn antagonist molecular population. In some embodiments, the tenth subpopulation comprises 0.5%-2.0%, 0.5%-1.5%, or 1.0%-1.5% of the FcRn antagonist molecular population.

[0146] In some embodiments, the eleventh subpopulation comprises less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the FcRn antagonist molecular population. In some embodiments, the eleventh subpopulation comprises about 2.0%, about 1.5%, about 1%, or about 0.5% of the FcRn antagonist molecular population. In some embodiments, the eleventh subpopulation comprises 2.0%, 1.5%, 1%, or 0.5% of the FcRn antagonist molecular population. In some embodiments, the eleventh subpopulation comprises 0.5%-2.0%, 0.5%-1.5%, or 1.0%-1.5% of the FcRn antagonist molecular population.

[0147] In some embodiments, the FcRn antagonist molecular population comprises one or more 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 as described in U.S. Patent Application No. 63 / 383,599, filed November 14, 2022, which is incorporated herein by reference in its entirety.

[0148] In one embodiment, the FcRn antagonist is efgartigimod (CAS Registry Number 1821402-21-4). The term "efgartigimod" as used herein may be interchangeable with "efgartigimod alpha". In some embodiments, efgartigimod is efgartigimod alpha-fcab.

[0149] In one embodiment, the anti-FcRn antibody is rozanolixizumab (UCB7665), nicalizumab (M281), onolizumab (ALXN1830 / SYNT001), or bartolizumab (IMVT-1401 / RVT1401 / HBM9161).

[0150] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of immunoglobulins to FcRn is nicalizumab, also known as M281. Nicalizumab is a full-length "Fc dead" IgG1 monoclonal antibody. Nicalizumab was administered by intravenous infusion in a Phase 2 clinical trial for the treatment of myasthenia gravis (MG), warm antibody autoimmune hemolytic anemia (WAIHA), and hemolytic disease of the fetus and newborn (HDFN). Nicalizumab contains the light chain (SEQ ID NO:4) and heavy chain (SEQ ID NO:5) sequences shown in Table 3 below (the VL region of SEQ ID NO:4 and the VH region of SEQ ID NO:5 are underlined):

[0151] Table 3. Heavy and light chain sequences of nicalizumab

[0152]

[0153] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of immunoglobulins to FcRn is rozanolixizumab, also known as UCB 7665. Rozanolixizumab is a full-length humanized IgG4 monoclonal antibody. Rozanolixizumab is administered by subcutaneous infusion in ongoing clinical trials for MG, immune thrombocytopenia (FTP), and chronic inflammatory demyelinating polyneuropathy (CIDP). Rozanolixizumab contains the light chain (SEQ ID NO:6) and heavy chain (SEQ ID NO:7) sequences shown in Table 4 below (the VL region of SEQ ID NO:6 and the VH region of SEQ ID NO:7 are underlined):

[0154] Table 4. Heavy and light chain sequences of rozanolixizumab

[0155]

[0156] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of an immunoglobulin to FcRn is onolizumab, also known as SYNT001. Onolizumab is another full-length humanized IgG4 monoclonal antibody. Onolizumab is administered by intravenous infusion in a Phase 2 clinical trial for the treatment of WAIHA. Onolizumab comprises the light chain (SEQ ID NO:8) and heavy chain (SEQ ID NO:9) sequences shown in Table 5 below (the VL region of SEQ ID NO:8 and the VH region of SEQ ID NO:9 are underlined):

[0157] Table 5. Heavy and light chain sequences of onolizumab

[0158]

[0159]

[0160] In one embodiment, the antibody that specifically binds to FcRn and inhibits the binding of the Fc region of an immunoglobulin to FcRn is bartolizumab, also known as IMVT1401 / RVT1401 / HBM9161. Bartolizumab is a full-length "Fc-null" IgG1 monoclonal antibody. Bartolizumab is administered by subcutaneous injection in an ongoing Phase 2 clinical trial for the treatment of MG and Graves' ophthalmopathy. Bartolizumab comprises the light chain (SEQ ID NO:10) and heavy chain (SEQ ID NO:11) sequences shown in Table 6 below (the VL region of SEQ ID NO:10 and the VH region of SEQ ID NO:11 are underlined):

[0161] Table 6. Heavy and light chain sequences of bartolizumab

[0162]

[0163] Pharmaceutical composition

[0164] In one aspect, the present disclosure provides a pharmaceutical composition comprising an FcRn antagonist, which is used in a method for treating LN. In certain embodiments, these compositions comprise or consist of a variant Fc region or an FcRn-binding fragment thereof that binds to FcRn with increased affinity and reduced pH-dependence relative to the native Fc region, particularly human FcRn. In other embodiments, the FcRn antagonist composition is an antibody or an 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 rate of degradation of the Fc-containing agents and a concomitant decrease in the serum levels of these agents.

[0165] In one embodiment, the FcRn antagonist is efgartigimod. Efgartigimod (ARGX-113) is a modified human immunoglobulin (Ig) γ (IgG)1-derived Fc, which is of the za allotype and binds to human FcRn with nanomolar affinity. Efgartigimod encompasses the IgG1 Fc region and has been engineered using the ABDEG TM technology to increase its affinity for FcRn at both physiological and acidic pHs. The increased affinity of efgartigimod for FcRn at both acidic and physiological pHs results in the blockade of FcRn-mediated IgG recycling.

[0166] Due to the increased affinity for FcRn at both acidic and neutral pHs, efgartigimod blocks the formation of the FcRn / IgG complex, which causes the degradation of endogenous IgG, including autoantibodies that cause IgG-mediated autoimmune diseases. This blockade of FcRn by efgartigimod results in a rapid and substantial reduction in autoantibody levels, which is the basis of a treatment strategy for 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 prevent the onset or progression of LN by reducing circulating immune complexes, thereby preventing their deposition in the glomeruli. Indeed, efgartigimod has been shown to reduce circulating immune complexes (Example 1; Figure 1 ).

[0167] Efgartigimod is being developed for both intravenous (IV) and subcutaneous (SC) administration routes.

[0168] For IV administration, in certain embodiments, efgartigimod can be administered in a formulation comprising sodium phosphate, sodium chloride, L-arginine hydrochloride, and polysorbate 80. In certain embodiments, efgartigimod can be administered in a formulation comprising approximately 25 mM sodium phosphate, approximately 100 mM sodium chloride, and approximately 150 mM L-arginine hydrochloride (pH 6.7), and approximately 0.02% (w / v) polysorbate 80. In certain embodiments, efgartigimod can 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 by intravenous infusion in a formulation comprising approximately 25 mM sodium phosphate, approximately 100 mM sodium chloride, and approximately 150 mM L-arginine hydrochloride (pH 6.7), and approximately 0.02% (w / v) polysorbate 80 over a period of about 2 hours in a total volume of about 250 mL. In certain embodiments, efgartigimod can be administered by intravenous infusion 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 over a period of 2 hours in a total volume of 250 mL. See, for example, WO2019110823A1, which is incorporated herein by reference in its entirety.

[0169] In certain embodiments, efgartigimod can be administered by intravenous infusion in a total volume of about 125 mL over a period of about 1 hour after dilution in a formulation comprising an aqueous solution containing approximately 25 mM sodium phosphate, approximately 100 mM sodium chloride, and approximately 150 mM L-arginine hydrochloride (pH of about 6.7), and approximately 0.02% (w / v) polysorbate 80. In certain embodiments, efgartigimod can be administered by intravenous infusion in a total volume of 125 mL over a period of 1 hour after dilution in a formulation comprising an aqueous solution containing 25 mM sodium phosphate, 100 mM sodium chloride, and 150 mM L-arginine hydrochloride (pH 6.7), and 0.02% (w / v) polysorbate 80.

[0170] In certain embodiments, efgartigimod can be administered in a formulation comprising an aqueous solution containing approximately 4 mM sodium phosphate, approximately 146 mM sodium chloride, approximately 24 mM L-arginine, and approximately 0.0032% (w / v) polysorbate 80 (pH of about 6.7). The formulation is administered by intravenous infusion over a period of about 1 hour in a total volume of about 125 mL. In certain embodiments, efgartigimod can be administered in a formulation comprising an aqueous solution containing 4 mM sodium phosphate, 146 mM sodium chloride, 24 mM L-arginine, and 0.0032% (w / v) polysorbate 80 (pH 6.7). The formulation is administered by intravenous infusion over a period of 1 hour in a total volume of 125 mL.

[0171] In certain embodiments, efgartigimod is administered via IV infusion and provided in a sterile, colorless, clear concentrate at a concentration of about 20 mg / mL. In certain embodiments, efgartigimod is administered via IV infusion and provided in a sterile, colorless, clear concentrate at a concentration of 20 mg / mL.

[0172] In certain embodiments, efgartigimod is administered via IV infusion and provided in vials (e.g., single-dose vials). 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 disodium hydrogen phosphate anhydrous, about 1.1 mg of sodium dihydrogen phosphate monohydrate, and water for injection (USP) having 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 disodium hydrogen phosphate anhydrous, 1.1 mg of sodium dihydrogen phosphate monohydrate, and water for injection (USP) having a pH of 6.7.

[0173] In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered by IV infusion at a dose of about 10 mg / kg. In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered by IV infusion at a dose of about 10 mg / kg over about one hour. In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered by IV infusion at a dose of about 10 mg / kg once weekly over about one hour. In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered by IV infusion at a dose of about 10 mg / kg once weekly for about 4 weeks. In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered by IV infusion at a dose of 10 mg / kg. In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered by IV infusion at a dose of 10 mg / kg over one hour. In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered by IV infusion at a dose of 10 mg / kg once weekly over one hour. In certain embodiments, for patients weighing less than 120 kg, efgartigimod is administered by IV infusion at a dose of 10 mg / kg once weekly for 4 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.

[0174] For SC administration, in certain embodiments, efgartigimod may be administered alone. Alternatively, for SC administration, in certain embodiments, efgartigimod may be co-formulated and administered with hyaluronidase, such as, in particular, rHuPH20. The co-formulated material will allow for a greater volume of SC administration.

[0175] In some embodiments, efgartigimod may be administered in a formulation comprising an aqueous solution containing 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 containing 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.

[0176] In some embodiments, agamod can be administered in a formulation comprising an aqueous solution containing 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 agamod. In some embodiments, agamod can be administered in a formulation comprising an aqueous solution containing 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 comprises 200 mg / ml agamod. rHuPH20 is a commercial product of Halozyme Recombinant agent (hyaluronidase human injection), called The product was approved by the FDA for marketing in the United States in December 2005. It is a tissue permeability regulator indicated as an adjuvant in SC fluid administration to achieve hydration, to increase the dispersion and absorption of other injected drugs, and to improve the reabsorption of radiopaque agents in SC urography.

[0177] rHuPH20 is a recombinant human hyaluronidase produced by Chinese hamster ovary (CHO) cells that have been genetically engineered to contain a DNA plasmid encoding a soluble fragment of human hyaluronidase (posterior head protein 20 [PH20]).

[0178] HZ202 rHuPH20 DS is currently and other biopharmaceuticals co-formulated with rHuPH20 DS. Thus, in certain embodiments, HZ202 rHuPH20 DS is used in an agamod / rHuPH20 co-formulated product for SC administration (ie, agamod PH20 SC).

[0179] Co-formulations, compositions, purposes and methods provided herein are soluble hyaluronidases.Soluble hyaluronidases include any enzymes secreted from cells and present in soluble form when expressed.Such soluble hyaluronidases include but are not limited to bacterial soluble hyaluronidases, non-human soluble hyaluronidases, such as cattle PH20 and sheep PH20, human soluble PH20 and variants thereof.Because glycosylation is important for the catalytic activity and stability of hyaluronidase, the soluble form of PH20 is usually produced using a protein expression system that promotes correct N-glycosylation to ensure that the polypeptide remains active.Such cells include, for example, Chinese hamster ovary (CHO) cells (e.g., DG44 CHO cells).

[0180] rHuPH20 refers to a composition produced when a nucleic acid encoding residues 36 - 482 of SEQ ID NO:32 is expressed in cells such as CHO cells, typically linked to a native or heterologous signal sequence (residues 1 - 35 of SEQ ID NO:32). rHuPH20 is produced by expressing a nucleic acid molecule, such as encoding amino acids 1 - 482 (listed in SEQ ID NO:32) in mammalian cells. The translation process removes the 35 - amino - acid signal sequence. As produced in culture medium, there is heterogeneity at the C - terminus such that the product called rHuPH20 includes a mixture of species that can include any one or more of the polypeptides 36 - 480, 36 - 481, and 36 - 482 of SEQ ID NO:32, as well as some shorter polypeptides of varying abundances. Typically, rHuPH20 is produced in cells (such as CHO cells (e.g., DG44 CHO cells)) that promote proper N - glycosylation to maintain 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 when expressed in mammalian cells and 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.

[0181] In some embodiments, the pharmaceutical formulation comprises an amount of FcRn antagonist from about 20 mg to about 20,000 mg. In some embodiments, the pharmaceutical formulation comprises an amount of FcRn antagonist from about 200 mg to about 20,000 mg. In some embodiments, the pharmaceutical formulation comprises an amount of FcRn antagonist from about 300 mg to about 6000 mg. In some embodiments, the pharmaceutical formulation comprises an amount of FcRn antagonist from about 750 mg to about 3000 mg. In some embodiments, the pharmaceutical formulation comprises an amount of FcRn antagonist from about 1000 mg to about 2500 mg. In some embodiments, the pharmaceutical formulation comprises an amount of FcRn antagonist from about 1000 mg to about 2000 mg.

[0182] In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of from 20 mg to 20,000 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of from 200 mg to 20,000 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of from 300 mg to 6000 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of from 750 mg to 3000 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of from 1000 mg to 2500 mg. In some embodiments, the pharmaceutical formulation comprises an FcRn antagonist in an amount of from 1000 mg to 2000 mg.

[0183] In some embodiments, the pharmaceutical formulation comprises about 1000 mg or about 2000 mg of an FcRn antagonist. In some embodiments, the pharmaceutical formulation comprises 1000 mg or 2000 mg of an FcRn antagonist. In some embodiments, the FcRn antagonist is efgartigimod.

[0184] In some embodiments, the pharmaceutical formulation comprises an amount of efgartigimod of from 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.

[0185] In some embodiments, the pharmaceutical formulation comprises efgartigimod at from about 10 mg / mL to about 200 mg / mL. In some embodiments, the pharmaceutical formulation comprises efgartigimod at 10 mg / mL to 200 mg / mL.

[0186] 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.

[0187] 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.

[0188] In some embodiments, the pharmaceutical formulation further comprises hyaluronidase. In some embodiments, the hyaluronidase is recombinant human hyaluronidase PH20 (rHuPH20).

[0189] Hyaluronidase can be present in the pharmaceutical formulation in any suitable amount. In one embodiment, the amount of hyaluronidase is from about 1000 U / ml to about 3000 U / ml. In one embodiment, the amount of hyaluronidase 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 is 2000 U / mL.

[0190] 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.

[0191] In some embodiments, the pharmaceutical formulation comprises at least about 5 U to at least about 100,000 U of endoglycoside hydrolase. In certain 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 endoglycoside hydrolase.

[0192] In some embodiments, the pharmaceutical formulation comprises about 20,000 U of endoglycoside hydrolase. In some embodiments, the pharmaceutical formulation comprises at least about 500 U / mL to at least about 5000 U / mL of endoglycoside hydrolase. In certain 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 endoglycoside hydrolase. In some embodiments, the pharmaceutical formulation comprises about 2000 U / mL of endoglycoside hydrolase.

[0193] In some embodiments, the endoglycosidase cleaves hyaluronic acid at the hexosaminide β(1–4) or (1–3) bond. In some embodiments, the endoglycosidase comprises the catalytic domain of hyaluronidase PH-20 (HuPH20), HYAL1, HYAL2, HYAL3, HYAL4, or HYALPS1. In some embodiments, the endoglycosidase 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 at least 100% sequence identity to amino acids 36-490 of SEQ ID NO:32. In some embodiments, the endoglycosidase comprises hyaluronidase. In some embodiments, the endoglycosidase comprises a hyaluronidase selected from the group consisting of HuPH20, HYAL1, HYAL2, HYAL3, HYAL4, any variant thereof, and any isoform thereof. In some embodiments, the endoglycosidase comprises rHuPH20 or a fragment thereof.

[0194] In some embodiments, the endoglycosidase 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 fragments thereof. In some embodiments, the endoglycosidase comprises a modified hyaluronidase that comprises one or more amino acid substitutions in the α-helical region relative to a wild-type hyaluronidase selected from the group consisting of HuPH20, HYAL1, HYAL2, HYAL3, HYAL4, HYALPS1, or fragments thereof. In some embodiments, the endoglycosidase 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 fragments thereof. In some embodiments, the endoglycosidase comprises a modified hyaluronidase wherein 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 fragments thereof. In some embodiments, the endoglycosidase comprises a modified rHuPH20, wherein the modified rHuPH20 comprises: i. one or more amino acid substitutions in the α-helical region, the linker region, or both the α-helical region and the linker region relative to wild-type rHuPH20; ii. deletion of one or more N-terminal amino acids, one or more C-terminal amino acids, or one or more N-terminal amino acids and one or more C-terminal amino acids relative to wild-type rHuPH20; or iii. both (i) and (ii).

[0195] As used herein, "hyaluronidase" refers to an enzyme capable of catalyzing the cleavage of hyaluronic acid. Hyaluronic acid is a repeating polymer of N-acetylglucosamine and glucuronic acid that is present in the subcutaneous space, contributes to the soluble gel-like component of the skin extracellular matrix, and is restored by rapid turnover (resynthesis). In some embodiments, the hyaluronidase comprises rHuPH20, which is a glycosylated 447-amino acid single-chain polypeptide that can locally depolymerize hyaluronic acid in the subcutaneous space at the site of injection on the skin. The depolymerization of hyaluronic acid by hyaluronidase is accomplished by hydrolysis of the polysaccharide polymer. The depolymerization of hyaluronic acid results in an instantaneous decrease in the viscosity of the gel-like phase of the extracellular matrix and an increase in hydraulic conductance, thereby facilitating the dispersion and absorption of adjunctive therapeutic agents. Thus, hyaluronidase (e.g., rHuPH20) can enhance the rate and convenience of subcutaneous delivery of injectable biologics and drugs by acting as a permeation enhancer. In certain embodiments, the hyaluronidase comprises ENHANZE TM .

[0196] In any of the above embodiments, the pharmaceutical formulation can be a unit dosage form.

[0197] In one embodiment, the unit dosage form comprises an FcRn antagonist in the form of a dry formulation for dissolution, such as a lyophilized powder, a freeze-dried powder, or an anhydrous concentrate. In one embodiment, the dry formulation is contained in an airtight sealed container, such as a vial, an ampoule, or a sachet.

[0198] In one embodiment, the unit dosage form comprises an FcRn antagonist in the form of a liquid formulation (e.g., in the form of an injection or infusion solution). In one embodiment, the liquid formulation is contained in an airtight 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.

[0199] In one embodiment, the unit dose per vial can 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 an FcRn antagonist in the range of about 500 mg to about 2500 mg or about 1000 mg to about 2000 mg. In one embodiment, these formulations can be adjusted to the desired concentration by adding a sterile diluent to each vial.

[0200] The formulations disclosed herein include bulk pharmaceutical compositions that can be used to manufacture pharmaceutical compositions (e.g., compositions suitable for administration to a subject or patient), and these pharmaceutical compositions can be used to prepare unit dosage forms. In one embodiment, the compositions of the present invention are pharmaceutical compositions. Such compositions contain a prophylactically or therapeutically effective amount of one or more prophylactic or therapeutic agents (e.g., the FcRn antagonist of the present invention or other prophylactic or therapeutic agents) and a pharmaceutically acceptable carrier. In one embodiment, these pharmaceutical compositions are formulated for subcutaneous administration to a subject.

[0201] Method

[0202] In one aspect, methods for treating LN using an FcRn antagonist are provided. In certain embodiments, the FcRn antagonist is efgartigimod. An important goal and feature of the methods disclosed herein is to prevent the progression of end-stage renal disease (ESRD) in LN patients. Other goals and features of the methods disclosed herein include, but are not limited to, patient survival, long-term preservation of kidney function, prevention of disease exacerbation, prevention of organ damage, management of comorbidities, and improvement of disease-related quality of life. Effective treatment of LN with an FcRn antagonist can include at least one of the elements of the group consisting of: early reduction of UPCR, improvement of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K score, and / or improvement of the 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 point-of-care urine test. SLEDAI-2K is a questionnaire that determines lupus disease activity. In some embodiments, a subject treated according to the methods provided herein experiences a complete renal response (CRR). In some embodiments, a subject treated according to the methods provided herein experiences a modified complete renal response (mCRR). In some embodiments, a subject treated according to the methods provided herein experiences a partial renal response (PRR). In some embodiments, a subject treated according to 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-binding circulating immune complexes.

[0203] As described herein, a complete renal response (CRR) in a subject is defined as an eGFR ≥ 60 mL / min / 1.73m 2 or no confirmed reduction in eGFR from baseline values > 20%, and UPCR ≤ 0.5 mg / mg.

[0204] As described herein, a modified complete renal response (mCRR) in a subject is defined as an eGFR ≥ 90 mL / min / 1.73m 2 or no confirmed reduction in eGFR from baseline values > 10%, and UPCR ≤ 0.5 mg / mg.

[0205] As described herein, a partial renal response (PRR) in a subject is defined as an eGFR ≥ 60 mL / min / 1.73m 2 or no confirmed reduction in eGFR from baseline values > 20%; and a ≥ 50% reduction in UPCR from baseline, and meeting one of the following conditions: if baseline UPCR is ≤ 3.0 mg / mg, then post-treatment UPCR is < 1.0 mg / mg, or if baseline UPCR is > 3.0 mg / mg, then post-treatment UPCR is < 3.0 mg / mg.

[0206] In some embodiments, LN may be characterized by a positive antinuclear antibody (ANA) test result in a subject (e.g., ANA titer ≥ 1:80). In some embodiments, LN may be characterized by anti-dsDNA (e.g., ≥ 30 IU / mL) or low complement levels (e.g., C3 < 0.9 g / L or C4 < 0.1 g / L) in a subject. In some embodiments, LN may be characterized by a UPCR ≥ 1.0 mg / mg in a subject. In some embodiments, LN may be characterized by an eGFR ≥ 60 mL / min / 1.73 m 2 In some embodiments, LN may be characterized by total serum IgG ≥ 6 g / L in a subject. In some embodiments, LN may be characterized by total serum IgG ≥ 4 g / L in a subject.

[0207] In some embodiments, the subject suffers from Class III or Class IV LN. In some embodiments, the subject does not suffer from Class III (C), IV-S (C) and IV-G (C) LN. In some embodiments, the subject suffers from Class I LN. In some embodiments, the subject suffers from Class II LN. In some embodiments, the subject suffers from Class III LN. In some embodiments, the subject suffers from Class IV LN. In some embodiments, the subject suffers from Class V LN. In some embodiments, the subject suffers from Class VI LN. In some embodiments, the subject suffers from Class III and Class V LN. In some embodiments, the subject suffers from Class IV and Class V LN.

[0208] 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 agamod.

[0209] 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.

[0210] 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.

[0211] 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.

[0212] In some embodiments, the FcRn antagonist is administered at a dose of from about 0.2 mg / kg to about 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of from about 2 mg / kg to about 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of from about 2 mg / kg to about 120 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of from about 3 mg / kg to about 60 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of from about 10 mg / kg to about 25 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod.

[0213] In some embodiments, the FcRn antagonist is administered at a dose of from 0.2 mg / kg to 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of from about 2 mg / kg to about 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of from 2 mg / kg to 120 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of from 3 mg / kg to 60 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of from 10 mg / kg to 25 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod.

[0214] 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 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. In some embodiments, the FcRn antagonist is efgartigimod.

[0215] 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, 50 mg / kg, 55 mg / kg, 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. In some embodiments, the FcRn antagonist is efgartigimod.

[0216] 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.

[0217] In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of about 0.2 mg / kg to about 200 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of about 2 mg / kg to about 200 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of about 2 mg / kg to about 120 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of about 3 mg / kg to about 60 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of about 10 mg / kg to about 25 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod.

[0218] In some embodiments, the FcRn antagonist is administered at 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. In some embodiments, the FcRn antagonist is agamod, for example, 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 is administered intravenously once a week or once every two weeks. In some embodiments, the FcRn antagonist is agamod.

[0219] 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, A dose of 55 mg / kg, 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 is administered intravenously once a week or once every two weeks. In some embodiments, the FcRn antagonist is igamod.

[0220] In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of about 10 mg / kg to about 30 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of about 10 mg / kg to about 25 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of about 10 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of about 15 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of about 20 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of about 25 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of about 30 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of 10 mg / kg to 30 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of 10 mg / kg to 25 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of 10 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of 15 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of 20 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of 25 mg / kg. In some embodiments, the FcRn antagonist is administered intravenously once a week or once every two weeks at a dose of 30 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod.

[0221] In some embodiments, the FcRn antagonist is administered intravenously once every two weeks for 52 weeks. In some embodiments, the FcRn antagonist is efgartigimod.

[0222] 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.

[0223] 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 3000 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.

[0224] In some embodiments, the FcRn antagonist is administered subcutaneously at a fixed dose 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, 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. In some embodiments, the FcRn antagonist is efgartigimod.

[0225] 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.

[0226] In some embodiments, the FcRn antagonist is administered subcutaneously once a week or once every two weeks at a fixed dose of about 750 mg to about 3000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week or once every two weeks at a fixed dose of about 1000 mg to about 2000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week or once every two weeks at a fixed dose of about 1000 mg or about 2000 mg. In some embodiments, the FcRn antagonist is efgartigimod.

[0227] In some embodiments, the FcRn antagonist is administered subcutaneously once a week or once every two weeks at a fixed dose of 750 mg to 3000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 750 mg to 3000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once every two weeks at a fixed dose of 750 mg to 3000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once every three weeks at a fixed dose of 750 mg to 3000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a month at a fixed dose of 750 mg to 3000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week or once every two weeks at a fixed dose of 1000 mg to 2000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week or once every two weeks at a fixed dose of 1000 mg or 2000 mg. In some embodiments, the FcRn antagonist is efgartigimod.

[0228] In some embodiments, the FcRn antagonist is first administered subcutaneously twice on the same day at a fixed dose of about 1000 mg. In some embodiments, the FcRn antagonist is first administered subcutaneously twice on the same day at a fixed dose of 1000 mg. In some embodiments, the FcRn antagonist is efgartigimod.

[0229] 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 once a week at a fixed dose of about 1250 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of about 1500 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of about 1750 mg. In some embodiments, the FcRn antagonist is efgartigimod.

[0230] In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 750 mg to 1750 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 800 mg to 1200 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 750 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 800 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 1000 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 1200 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 1250 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 1500 mg. In some embodiments, the FcRn antagonist is administered subcutaneously once a week at a fixed dose of 1750 mg. In some embodiments, the FcRn antagonist is efgartigimod.

[0231] 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.

[0232] 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.

[0233] In some embodiments, the FcRn antagonist is administered intravenously first and then subcutaneously. In some embodiments, the FcRn antagonist is administered intravenously first and then subcutaneously at a fixed dose of 100 mg to 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 intravenously first and then 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.

[0234] In some embodiments, one or more doses of the FcRn antagonist are administered intravenously and subsequent doses of the FcRn antagonist are administered subcutaneously. In some embodiments, one or more doses of the FcRn antagonist are administered intravenously and subsequent doses of the FcRn antagonist are administered subcutaneously at a fixed dose of 100 mg to 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, one or more doses of the FcRn antagonist are administered intravenously and subsequent doses of the FcRn antagonist are 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.

[0235] 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.

[0236] In some embodiments, the FcRn antagonist is rozanolixizumab. In some embodiments, rozanolixizumab is administered subcutaneously or intravenously. In some embodiments, rozanolixizumab is administered once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks 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.

[0237] In some embodiments, rozanolixizumab is administered once weekly 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 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 63 mg / 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 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.

[0238] In some embodiments, rozanolixizumab is administered once every two weeks 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 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 63 mg / 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 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.

[0239] In some embodiments, rozanolixizumab is administered once every three weeks 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 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 63 mg / 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 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.

[0240] In some embodiments, rozanolixizumab is administered once every four weeks 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 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 63 mg / 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 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.

[0241] In some embodiments, rozanolixizumab is administered once monthly 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 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 63 mg / 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 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.

[0242] In some embodiments, the FcRn antagonist is nicalizumab. In some embodiments, nicalizumab is administered subcutaneously or intravenously. In some embodiments, nicalizumab is administered once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks 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.

[0243] In some embodiments, nikalimab is administered once a week 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 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 63 mg / 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 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.

[0244] In some embodiments, nikalimab is administered once every two weeks 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 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 63 mg / 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 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.

[0245] In some embodiments, nikalimab is administered once every three weeks 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 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 63 mg / 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 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.

[0246] In some embodiments, nikalimab is administered once every four weeks 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 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 63 mg / 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 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.

[0247] In some embodiments, nikalimab is administered once a month 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 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 63 mg / 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 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.

[0248] In some embodiments, the FcRn antagonist is onorlimab. In some embodiments, onorlimab is administered subcutaneously or intravenously. In some embodiments, onorlimab is administered once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks 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.

[0249] In some embodiments, oncolizumab is administered once weekly 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 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 63 mg / 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 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.

[0250] In some embodiments, oncolizumab is administered once every two weeks 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 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 63 mg / 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 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.

[0251] In some embodiments, oncolizumab is administered once every three weeks 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 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 63 mg / 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 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.

[0252] In some embodiments, oncolizumab is administered once every four weeks 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 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 63 mg / 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 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.

[0253] In some embodiments, oncolizumab is administered once monthly 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 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 63 mg / 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 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.

[0254] In some embodiments, onurelizumab is administered intravenously at a dose of about 30 mg / kg once a week for three weeks, and then intravenously at a dose of 10 mg / kg every other week.

[0255] In some embodiments, the FcRn antagonist is batoclimab. In some embodiments, batoclimab is administered subcutaneously or intravenously. In some embodiments, batoclimab is administered once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks 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.

[0256] In some embodiments, bartolimab is administered once a week 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 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 63 mg / 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 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.

[0257] In some embodiments, bartolimab is administered once every two weeks 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 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 63 mg / 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 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.

[0258] In some embodiments, bartolimab is administered once every three weeks 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 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 63 mg / 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 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.

[0259] In some embodiments, bartolimab is administered once every four weeks 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 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 63 mg / 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 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.

[0260] In some embodiments, bartolizumab is administered once monthly 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 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 63 mg / 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 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.

[0261] In some embodiments, the method further comprises administering to the subject a compound represented as the LN standard. In some embodiments, the method further comprises administering to the subject an effective amount of one or more of the following compounds: glucocorticoids, mycophenolate mofetil (MMF), mycophenolic acid (MPA), angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and / or hydroxychloroquine.

[0262] In one embodiment, the method further comprises administering to the subject an effective amount of corticosteroids and / or immunosuppressants. In one embodiment, the method further comprises administering to the subject an effective amount of corticosteroids. In one embodiment, the method further comprises administering to the subject an effective amount of glucocorticoids. In one embodiment, the method further comprises administering to the subject an effective amount of glucocorticoids intravenously and / or administering to the subject an effective amount of glucocorticoids orally. In one embodiment, the method further comprises administering glucocorticoids intravenously to the subject and administering an effective amount of glucocorticoids orally to the subject.

[0263] In one embodiment, the method further comprises administering to the subject an effective amount of prednisone. In one embodiment, the method further comprises administering prednisone to the subject 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 prednisone to the subject 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 prednisone to the subject 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 prednisone to the subject 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 prednisone to the subject at a dose of 0.5 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. 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, prednisone is administered orally.

[0264] In one embodiment, the method further comprises administering to the subject an effective amount of methylprednisolone. In one embodiment, the method further comprises administering methylprednisolone to the subject at a dose of 100 mg to 1250 mg for up to three days. In one embodiment, the method further comprises administering methylprednisolone to the subject at a dose of 150 mg to 1200 mg for up to three days. In one embodiment, the method further comprises administering methylprednisolone to the subject at a dose of 200 mg to 1100 mg for up to three days. In one embodiment, the method further comprises administering methylprednisolone to the subject at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the method further comprises administering methylprednisolone to the subject at a dose of 0.25 g / day to 0.5 g / day. In one embodiment, the method further comprises administering methylprednisolone to the subject at a dose of 0.25 g / day to 0.5 g / day for one to three days. In one embodiment, methylprednisolone is administered intravenously.

[0265] In one embodiment, the method further comprises orally administering to the subject an effective amount of prednisone and intravenously administering to the subject an effective amount of methylprednisolone. In one embodiment, the method further comprises orally administering prednisone to the subject at a dose of 10 mg / day to 60 mg / day, up to 1 mg / kg / day, and intravenously administering methylprednisolone to the subject at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the method further comprises orally administering prednisone to the subject at a dose of 0.5 mg / kg / day to 1 mg / kg / day, and intravenously administering methylprednisolone to the subject at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the method further comprises orally administering prednisone to the subject at a dose of 0.6 mg / kg / day to 1 mg / kg / day, up to 80 mg / day, and intravenously administering methylprednisolone to the subject at a dose of 0.25 g / day to 0.5 g / day for one to three days.

[0266] 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 intravenously administering cyclophosphamide to the subject at a dose of 500 mg every two weeks. In one embodiment, the method further comprises intravenously administering cyclophosphamide to the subject at a dose of 500 mg every two weeks for six months. In one embodiment, the method further comprises orally administering cyclophosphamide to the subject at a dose of 0.5 g / m 2 to 1 g / m 2 once a month. In one embodiment, the method further comprises orally administering cyclophosphamide to the subject at a dose of 0.5 g / m 2 to 1 g / m 2 once a month for six months.

[0267] 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, wherein the trough level is about 5.5 ng / mL (6.8 nmol / L). In one embodiment, the method further comprises administering to the subject tacrolimus and a mycophenolic acid analogue, wherein the trough level is about 5.5 ng / mL (6.8 nmol / L). In one embodiment, the method further comprises administering to the subject tacrolimus and a mycophenolic acid analogue for 24 months, wherein the trough level is about 5.5 ng / mL (6.8 nmol / L). In one embodiment, in subjects with a serum creatinine (SCr) level below 3 mg / dL (265 μmol / L), the method further comprises administering to the subject tacrolimus and a mycophenolic acid analogue for 24 months, wherein the trough level is about 5.5 ng / mL (6.8 nmol / L). In one embodiment, the method further comprises administering to the subject an effective amount of voriconazole. In one embodiment, the method further comprises administering voriconazole to the subject at a dose of 23.7 mg twice a day. In one embodiment, the method further comprises administering voriconazole and a mycophenolic acid analogue to the subject at a dose of 23.7 mg twice a day. In one embodiment, the method further comprises administering voriconazole and a mycophenolic acid analogue to the subject at a dose of 23.7 mg twice a day for 52 weeks. In one embodiment, in subjects with an eGFR greater than 45 mL / min per 1.73 m 2 of body surface area, the method further comprises administering voriconazole and a mycophenolic acid analogue to the subject at a dose of 23.7 mg twice a day for 52 weeks.

[0268] In one embodiment, when the subject is administered an FcRn antagonist, the dose of prednisone is reduced to a dose of 7.5 mg / day within 12 weeks.

[0269] In one embodiment, the method further comprises administering to the subject an effective amount of mycophenolate mofetil (MMF), mycophenolic acid (MPA) or an analogue thereof. In one embodiment, the method further comprises administering to the subject a daily dose of MMF, MPA or an analogue thereof. In one embodiment, the dose of MMF or MPA is increased to a maximum of 1.5 g or 2 g / day or an equivalent dose in divided doses over four weeks. In one embodiment, the method further comprises orally administering MMF to the subject at a dose of 1 g to 1.5 g twice a day. In one embodiment, the method further comprises orally administering mycophenolic acid to the subject at a dose of 0.72 g to 1.08 g twice a day.

[0270] In one embodiment, the method further comprises administering to the subject an effective amount of a B-lymphocyte targeting biologic. Examples of B-lymphocyte targeting 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 belimumab to the subject at a dose of 10 mg / kg, once every two weeks for a total of three administrations, followed by subsequent doses once every four weeks. In one embodiment, the method further comprises intravenously administering belimumab and a mycophenolic acid analogue to the subject at a dose of 10 mg / kg, once every two weeks for a total of three administrations, followed by subsequent doses once every four weeks. In one embodiment, the method further comprises intravenously administering belimumab and cyclophosphamide to the subject at a dose of 10 mg / kg, once every two weeks for a total of three administrations, followed by subsequent doses once every four weeks, cyclophosphamide. In one embodiment, the method further comprises intravenously administering belimumab to the subject at a dose of 10 mg / kg, once every two weeks for a total of three administrations, followed by subsequent doses once every four weeks, 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 rituximab to the subject at a dose of 1 g on day 1 and day 15 as additional treatment for refractory cases or corticosteroid minimization. In one embodiment, the method further comprises administering to the subject an effective amount of obinutuzumab.

[0271] In some embodiments, the FcRn antagonist is intravenously administered once every two weeks for 52 weeks, in combination with MMF or MPA and glucocorticoid therapy. In some embodiments, the FcRn antagonist is efgartigimod.

[0272] In one embodiment, the method further comprises administering to the subject an effective amount of an ACEi or ARB.

[0273] 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, hydroxychloroquine is administered for 24 weeks. In one embodiment, hydroxychloroquine is administered for at least 24 weeks.

[0274] In one embodiment, the subject was previously treated with an induction therapy for LN. In one embodiment, the subject has received an induction therapy for LN. In one embodiment, the induction therapy began within 60 days prior to administering the FcRn antagonist to the subject. In one embodiment, the induction therapy began less than 60 days prior to administering the FcRn antagonist to the subject. In one embodiment, the induction therapy began at least three days, but no more than 60 days (e.g., three days, four days, five days, ten days, fifteen days, twenty days, twenty-five days, thirty days, thirty-five days, forty days, forty-five days, fifty days, fifty-five days, sixty days) prior to administering the FcRn antagonist to the subject. In one embodiment, the subject received an induction therapy within 60 days prior to administering the FcRn antagonist to the subject. In one embodiment, the method comprises administering to the subject an effective amount of a human FcRn antagonist, after the subject has received an 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 after the subject has received an induction therapy for LN.

[0275] In one embodiment, the subject was previously treated with an effective amount of a corticosteroid and / or an immunosuppressant. In one embodiment, the subject was 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 a glucocorticoid orally to the subject. In one embodiment, the induction therapy comprises administering to the subject an effective amount of a glucocorticoid intravenously and administering a glucocorticoid orally to the subject.

[0276] In one embodiment, the subject was previously treated with prednisone in an effective amount. In one embodiment, the subject was 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 was 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 was 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 was 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 was 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 an effective amount of prednisone to the subject. In one embodiment, the induction therapy comprises administering prednisone to the subject at a dose of 7.5 mg / day to 75 mg / day, up to 1 mg / kg / day. In one embodiment, the induction therapy comprises administering prednisone to the subject at a dose of 8 mg / day to 72 mg / day, up to 1 mg / kg / day. In one embodiment, the induction therapy comprises administering prednisone to the subject at a dose of 9 mg / day to 66 mg / day, up to 1 mg / kg / day. In one embodiment, the induction therapy comprises administering prednisone to the subject at a dose of 10 mg / day to 60 mg / day, up to 1 mg / kg / day. In one embodiment, the induction therapy comprises administering prednisone to the subject at a dose of 0.5 mg / kg / day to 1 mg / kg / day. In one embodiment, the induction therapy comprises administering prednisone to the subject 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, prednisone is administered orally.

[0277] In one embodiment, the subject was previously treated with an effective amount of methylprednisolone. In one embodiment, the subject was previously treated with methylprednisolone at a dose of 100 mg to 1250 mg for up to three days. In one embodiment, the subject was previously treated with methylprednisolone at a dose of 150 mg to 1200 mg for up to three days. In one embodiment, the subject was previously treated with methylprednisolone at a dose of 200 mg to 1100 mg for up to three days. In one embodiment, the subject was previously treated with methylprednisolone at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the subject was 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 methylprednisolone to the subject 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 an effective amount of methylprednisolone to the subject. In one embodiment, the induction therapy comprises administering methylprednisolone to the subject at a dose of 100 mg to 1250 mg for up to three days. In one embodiment, the induction therapy comprises administering methylprednisolone to the subject at a dose of 150 mg to 1200 mg for up to three days. In one embodiment, the induction therapy comprises administering methylprednisolone to the subject at a dose of 200 mg to 1100 mg for up to three days. In one embodiment, the induction therapy comprises administering methylprednisolone to the subject at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the induction therapy comprises administering methylprednisolone to the subject at a dose of 0.25 g / day to 0.5 g / day. In one embodiment, the method further comprises administering methylprednisolone to the subject at a dose of 0.25 g / day to 0.5 g / day for one to three days. In one embodiment, methylprednisolone is administered intravenously.

[0278] In one embodiment, the subject was previously treated orally with an effective amount of prednisone and intravenously with methylprednisolone. In one embodiment, the subject was previously treated orally with prednisone at a dose of 10 mg / day to 60 mg / day, up to 1 mg / kg / day, and methylprednisolone was administered intravenously at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the induction therapy includes orally administering prednisone and intravenously administering methylprednisolone to the subject. In one embodiment, the subject was previously treated orally with prednisone at a dose of 0.6 mg / kg / day to 1 mg / kg / day, up to 80 mg / day, and methylprednisolone was administered intravenously at a dose of 0.25 g / day to 0.5 g / day for one to three days. In one embodiment, the induction therapy includes orally administering an effective amount of prednisone to the subject at a dose of 10 mg / day to 60 mg / day, up to 1 mg / kg / day, and methylprednisolone was administered intravenously at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the induction therapy includes orally administering prednisone to the subject at a dose of 0.5 mg / kg / day to 1 mg / kg / day, and methylprednisolone was administered intravenously at a dose of 500 mg to 1000 mg for up to three days. In one embodiment, the induction therapy includes orally administering prednisone to the subject at a dose of 0.6 mg / kg / day to 1 mg / kg / day, up to 80 mg / day, and methylprednisolone was administered intravenously at a dose of 0.25 g / day to 0.5 g / day for one to three days.

[0279] In one embodiment, the subject was previously treated with an effective amount of cyclophosphamide. In one embodiment, the subject was previously treated with an effective amount of cyclophosphamide for up to six months. In one embodiment, the subject was previously treated with cyclophosphamide at a dose of 500 mg intravenously every two weeks. In one embodiment, the subject was previously treated with cyclophosphamide at a dose of 500 mg intravenously every two weeks for six months. In one embodiment, the subject was previously treated orally with cyclophosphamide at a dose of 0.5 g / m 2 to 1 g / m 2 of cyclophosphamide. In one embodiment, the subject was previously treated orally with cyclophosphamide at a dose of 0.5 g / m 2 to 1 g / m 2 of cyclophosphamide for six months. In one embodiment, the induction therapy includes administering an effective amount of cyclophosphamide to the subject. In one embodiment, the induction therapy includes administering an effective amount of cyclophosphamide to the subject for up to six months. In one embodiment, the induction therapy includes administering cyclophosphamide intravenously to the subject at a dose of 500 mg every two weeks. In one embodiment, the induction therapy includes administering cyclophosphamide intravenously to the subject at a dose of 500 mg every two weeks for six months. In one embodiment, the induction therapy includes administering cyclophosphamide at a dose of 0.5 g / m 2 to 1 g / m 2Cyclophosphamide is orally administered to the subject once a month at a dose of. In one embodiment, the induction therapy comprises administering cyclophosphamide orally to the subject once a month for six months at a dose of 0.5 g / m 2 to 1 g / m 2 at a dose of.

[0280] In one embodiment, the subject has been 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 has been previously treated with tacrolimus, wherein the trough level is approximately 5.5 ng / mL (6.8 nmol / L). In one embodiment, the subject has been previously treated with tacrolimus and a mycophenolic acid analogue, wherein the trough level is approximately 5.5 ng / mL (6.8 nmol / L). In one embodiment, the subject has been previously treated with tacrolimus and a mycophenolic acid analogue for 24 months, wherein the trough level is approximately 5.5 ng / mL (6.8 nmol / L). In one embodiment, among subjects with an SCr level below 3 mg / dL (265 μmol / L), the subject has been previously treated with tacrolimus and a mycophenolic acid analogue for 24 months, wherein the trough level is approximately 5.5 ng / mL (6.8 nmol / L). In one embodiment, the subject has been previously treated with an effective amount of voriconazole. In one embodiment, the subject has been previously treated with voriconazole at a dose of 23.7 mg twice a day. In one embodiment, the subject has been previously treated with voriconazole at a dose of 23.7 mg and a mycophenolic acid analogue twice a day. In one embodiment, the subject has been previously treated with voriconazole at a dose of 23.7 mg and a mycophenolic acid analogue twice a day for 52 weeks. In one embodiment, among subjects with an eGFR greater than 45 mL / min per 1.73 m 2Among the subjects, the subjects were previously treated with voriconazole and mycophenolic acid analog at a dose of 23.7 mg twice a day for 52 weeks. In one embodiment, the induction therapy includes administering to the subject an effective amount of a calcineurin inhibitor. In one embodiment, the method further includes administering to the subject an effective amount of tacrolimus. In one embodiment, the induction therapy includes administering tacrolimus to the subject, wherein the trough level is approximately 5.5 ng / mL (6.8 nmol / L). In one embodiment, the induction therapy includes administering tacrolimus and mycophenolic acid analog to the subject, wherein the trough level is approximately 5.5 ng / mL (6.8 nmol / L). In one embodiment, the induction therapy includes administering tacrolimus and mycophenolic acid analog to the subject for 24 months, wherein the trough level is approximately 5.5 ng / mL (6.8 nmol / L). In one embodiment, among subjects with an SCr level below 3 mg / dL (265 μmol / L), the induction therapy includes administering tacrolimus and mycophenolic acid analog to the subject for 24 months, wherein the trough level is approximately 5.5 ng / mL (6.8 nmol / L). In one embodiment, the induction therapy includes administering to the subject an effective amount of voriconazole. In one embodiment, the induction therapy includes administering voriconazole to the subject at a dose of 23.7 mg twice a day. In one embodiment, the induction therapy includes administering voriconazole and mycophenolic acid analog to the subject at a dose of 23.7 mg twice a day. In one embodiment, the induction therapy includes administering voriconazole and mycophenolic acid analog to the subject at a dose of 23.7 mg twice a day for 52 weeks. In one embodiment, among subjects with an eGFR greater than 45 mL / min per 1.73 m 2 the induction therapy includes administering voriconazole and mycophenolic acid analog to the subject at a dose of 23.7 mg twice a day for 52 weeks.

[0281] In one embodiment, when the subject is administered an FcRn antagonist, the prednisone dose is gradually reduced to a dose of 7.5 mg / day over 12 weeks. In one embodiment, the initial oral prednisone dose is from 0.5 mg / kg / day to 1 mg / kg / day, not exceeding 60 mg / day. In one embodiment, the initial oral prednisone dose in Table S2 is rounded to the nearest 10 mg increment, and prednisone tapering is initiated 2 weeks after the start of oral prednisone according to the schedule set forth in Table S2. In some embodiments, for a subject administered an FcRn antagonist who experiences LN exacerbation, the subject may be administered prednisone for 2 weeks after LN exacerbation at a dose of from 0.5 mg / kg / day to 1 mg / kg / day, not exceeding 60 mg / day. In one embodiment, prednisone after LN exacerbation is gradually reduced to a dose of 10 mg / day or less over 6 weeks. In one embodiment, prednisone after LN exacerbation is gradually reduced to a dose of 10 mg / day or less over 6 weeks according to the schedule set forth in Table S3. In some embodiments, for a subject administered an FcRn antagonist who experiences extra-renal exacerbation, the subject may be administered prednisone after extra-renal exacerbation at a dose of up to 1 mg / kg / day, not exceeding 60 mg / day. In one embodiment, prednisone after extra-renal exacerbation is gradually reduced to a dose of 7.5 mg / day over approximately 12 weeks. In one embodiment, prednisone after extra-renal exacerbation is gradually reduced to a dose of 7.5 mg / day over approximately 12 weeks according to the schedule set forth in Table S4.

[0282] In one embodiment, the subject was previously treated with an effective amount of MMF, MPA or an analogue thereof. In one embodiment, induction therapy comprises administering to the subject an effective amount of MMF, MPA or an analogue thereof. In one embodiment, the dose of MMF or MPA is increased in divided doses over four weeks to a maximum of 1.5 g or 2 g / day or an equivalent dose. In one embodiment, the subject was previously treated orally with MMF at a dose of 1 g to 1.5 g twice a day. In one embodiment, the subject was previously treated orally with mycophenolic acid at a dose of 0.72 g to 1.08 g twice a day. In one embodiment, induction therapy comprises orally administering MMF to the subject at a dose of 1 g to 1.5 g twice a day. In one embodiment, induction therapy comprises orally administering mycophenolic acid to the subject at a dose of 0.72 g to 1.08 g twice a day. In one embodiment, the method further comprises administering to the subject a daily dose of an effective amount of MMF, MPA or an analogue thereof. In one embodiment, the dose of MMF, MPA or an analogue thereof is increased in divided doses over four weeks to a maximum of 1.5 g or 2 g / day or an equivalent dose.

[0283] In one embodiment, the subject was previously treated with an effective amount of a B-lymphocyte targeting biologic. Examples of B-lymphocyte targeting biologics include, but are not limited to, belimumab, rituximab, and obinutuzumab. In one embodiment, the subject was previously treated with an effective amount of belimumab. In one embodiment, the subject was previously treated with belimumab intravenously at a dose of 10 mg / kg, three times every two weeks, followed by subsequent doses every four weeks. In one embodiment, the subject was previously treated with belimumab intravenously at a dose of 10 mg / kg and a mycophenolic acid analogue, three times every two weeks, followed by subsequent doses every four weeks. In one embodiment, the subject was previously treated with belimumab intravenously at a dose of 10 mg / kg and cyclophosphamide, three times every two weeks, followed by subsequent doses every four weeks. In one embodiment, the subject was previously treated with belimumab intravenously at a dose of 10 mg / kg, three times every two weeks, followed by subsequent doses every four weeks, and cyclophosphamide at a dose of 500 mg 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 day 1 and day 15 as additional treatment for refractory cases or corticosteroid minimization. In one embodiment, the subject was previously treated with an effective amount of obinutuzumab.

[0284] In one embodiment, the induction therapy comprises administering to a subject an effective amount of a B-lymphocyte targeting biologic. Examples of B-lymphocyte targeting biologics include, but are not limited to, belimumab, rituximab, and obinutuzumab. In one embodiment, the induction therapy comprises administering to a subject an effective amount of belimumab. In one embodiment, the induction therapy comprises intravenously administering belimumab to a subject at a dose of 10 mg / kg every two weeks for a total of three administrations, followed by subsequent doses every four weeks. In one embodiment, the induction therapy comprises intravenously administering belimumab and a mycophenolic acid analogue to a subject at a dose of 10 mg / kg every two weeks for a total of three administrations, followed by subsequent doses every four weeks. In one embodiment, the induction therapy comprises intravenously administering belimumab and cyclophosphamide to a subject at a dose of 10 mg / kg every two weeks for a total of three administrations, followed by subsequent doses every four weeks, cyclophosphamide. In one embodiment, the induction therapy comprises intravenously administering belimumab to a subject at a dose of 10 mg / kg every two weeks for a total of three administrations, followed by subsequent doses every four weeks, and administering cyclophosphamide at a dose of 500 mg every two weeks for six months. In one embodiment, the induction therapy comprises administering to a subject an effective amount of rituximab. In one embodiment, the induction therapy comprises administering rituximab to a subject at a dose of 1 g on day 1 and day 15 as additional therapy for refractory cases or corticosteroid minimization. In one embodiment, the induction therapy comprises administering to a subject an effective amount of obinutuzumab.

[0285] In one embodiment, the subject was previously treated with an ACEi or an ARB. In one embodiment, the method further comprises administering an ACEi or an ARB to the subject.

[0286] In one embodiment, the subject was previously treated with hydroxychloroquine at a maximum dose of 5 mg / kg / day. In one embodiment, the method further comprises administering hydroxychloroquine to the subject at a maximum dose of 5 mg / kg / day. In one embodiment, hydroxychloroquine is administered for 24 weeks. In one embodiment, hydroxychloroquine is administered for at least 24 weeks.

[0287] In some embodiments, the treatment of LN is characterized in that the subject exhibits an eGFR of 25 mL / min / 1.73m 2 In some embodiments, the subject exhibits at least 30 mL / min / 1.73m 2 at least 35 mL / min / 1.73m 2 at least 40 mL / min / 1.73m 2 at least 45 mL / min / 1.73m 2 at least 50 mL / min / 1.73m 2, at least 55 mL / min / 1.73m 2 , at least 60 mL / min / 1.73m 2 , at least 65 mL / min / 1.73m 2 , at least 70 mL / min / 1.73m 2 , at least 75 mL / min / 1.73m 2 , at least 80 mL / min / 1.73m 2 , at least 85 mL / min / 1.73m 2 , at least 90 mL / min / 1.73m 2 , at least 95 mL / min / 1.73m 2 , at least 100 mL / min / 1.73m 2 , at least 105 mL / min / 1.73m 2 , at least 110 mL / min / 1.73m 2 , at least 115 mL / min / 1.73m 2 , at least 120 mL / min / 1.73m 2 of eGFR. In some embodiments, the subject exhibits at least 60 mL / min / 1.73m 2 of eGFR. In some embodiments, treatment of LN is characterized in that the subject exhibits an eGFR that is less than 20% lower compared to the baseline eGFR obtained from the subject prior to administration of the FcRn antagonist. In some embodiments, compared to the baseline eGFR obtained from the subject prior to administration of the FcRn antagonist, the subject exhibits a reduction in eGFR of less than 15%, less than 10%, less than 5%, less than 1%.

[0288] In some embodiments, after administration of the FcRn antagonist to the subject, the subject exhibits at least 60 mL / min / 1.73m 2 of post - administration eGFR. In some embodiments, after administration of the FcRn antagonist to the subject, the subject exhibits a post - administration eGFR that is less than 20% lower compared to the 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 administration of the FcRn antagonist to the subject. In some embodiments, the post - administration eGFR is measured 52 weeks after administration of the FcRn antagonist to the subject.

[0289] In some embodiments, after administration of the FcRn antagonist to the subject, the subject exhibits at least 90 mL / min / 1.73m 2Post - administration eGFR. In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post - administration eGFR that is less than 10% lower compared to the baseline eGFR obtained from the subject before administering 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.

[0290] In some embodiments, the treatment of LN is characterized in that the subject exhibits a UPCR of at most 0.5 mg / mg. In 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, 0.1 mg / mg.

[0291] In some embodiments, the treatment of LN is characterized in that the subject exhibits a UPCR that is at least 50% lower compared to the baseline UPCR obtained from the subject before administering the FcRn antagonist, and if the baseline UPCR is at most 3 mg / mg, then the post - administration UPCR is less than 1 mg / mg. In some embodiments, the treatment of LN is characterized in that the subject exhibits a UPCR that is at least 50% lower compared to the baseline UPCR obtained from the subject before administering the FcRn antagonist, and if the baseline UPCR is greater than 3 mg / mg, then the post - administration UPCR is less than 3 mg / mg.

[0292] 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 - binding circulating immune complexes. In some embodiments, after administering one or more of the treatments described herein, 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%. In some embodiments, after administering one or more of the treatments described herein, circulating immune complexes are undetectable in the subject. In some embodiments, the treatment is administering an effective amount of an FcRn antagonist. In some embodiments, the treatment is administering an effective amount of efgartigimod.

[0293] 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 at least 50% lower than the baseline UPCR obtained from the subject prior to administering the FcRn antagonist, and wherein 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 at least 50% lower than the baseline UPCR obtained from the subject prior to administering the FcRn antagonist, and wherein if the baseline UPCR is greater 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, the post - administration UPCR is measured 52 weeks after administering the FcRn antagonist to the subject.

[0294] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post - administration Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) - 2K score that is lower than the baseline SLEDAI - 2K score obtained from the subject prior to 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.

[0295] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post - administration level of serum autoantibodies that is lower than the baseline level of serum autoantibodies obtained from the subject prior to administering the FcRn antagonist. In some embodiments, the post - administration level of serum autoantibodies is 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% lower than the baseline level of serum autoantibodies obtained from the subject prior to 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.

[0296] 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 prior to administering the FcRn antagonist. In some embodiments, 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 prior to 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 - binding circulating immune complexes.

[0297] In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post - administration level of circulating immune complexes that is reduced compared to the baseline level of circulating immune complexes obtained from the subject prior to administering the FcRn antagonist. In some embodiments, the circulating immune complexes are selected from the group consisting of C3, C4, CH50, and C1q - binding circulating immune complexes. In some embodiments, the post - administration level 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% compared to the baseline level of circulating immune complexes obtained from the subject prior to administering the FcRn antagonist. In some embodiments, the post - administration level of circulating immune complexes is measured 24 weeks after administering the FcRn antagonist to the subject. In some embodiments, the post - administration level of circulating immune complexes is measured 52 weeks after administering the FcRn antagonist to the subject.

[0298] 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 prior to 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 prior to 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.

[0299] In some embodiments, after administering an FcRn antagonist to a subject, the albumin of the subject does not decrease after administration of the FcRn antagonist as compared to the baseline level of albumin at baseline. In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post - administration level of albumin that does not decrease as compared to the baseline level of albumin obtained from the subject prior to administering the FcRn antagonist. In one embodiment, an albumin decrease of less than about 1%, 2%, 3%, 4%, or 5% is observed as compared to the baseline albumin level. In one embodiment, an albumin decrease of less than about 10% is observed as 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.

[0300] In some embodiments, after administering an FcRn antagonist to a subject, the serum albumin of the subject does not decrease after administration of the FcRn antagonist as compared to the baseline level of serum albumin at baseline. In some embodiments, after administering an FcRn antagonist to a subject, the subject exhibits a post - administration level of serum albumin that does not decrease as compared to the baseline level of serum albumin obtained from the subject prior to administering the FcRn antagonist. In one embodiment, a serum albumin decrease of less than about 1%, 2%, 3%, 4%, or 5% is observed as compared to the baseline serum albumin level. In one embodiment, a serum albumin decrease of less than about 10% is observed as compared to the baseline serum albumin level. In some embodiments, the post - administration level of serum albumin is measured 24 weeks after administering the FcRn antagonist to the subject. In some embodiments, the post - administration level of serum albumin is measured 52 weeks after administering the FcRn antagonist to the subject.

[0301] 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 an Asian.

[0302] Examples

[0303] The following examples are provided by way of illustration and not limitation.

[0304] Example 1: Study on the Efficacy of Efgartigimod in Reducing Circulating Immune Complexes

[0305] Immune complexes are found in healthy individuals, but their formation can be expected to be elevated in autoimmune diseases and to drive and / or exaggerate their pathology to some extent. Efgartigimod is an engineered Fc fragment that inhibits FcRn function by outcompeting endogenous IgG binding, resulting in decreased IgG circulation and increased IgG degradation. Since the half-life of immune complexes (predominantly containing IgG) may also be affected by FcRn biology, circulating immune complex (CIC) levels were investigated as part of an open-label, adaptive extension phase 2 trial of efgartigimod in the treatment of mild to moderate pemphigus vulgaris (PV) or pemphigus foliaceus (PF) (ClinicalTrials.gov: NCT03334058; Maho-Vaillant M et al. Front Immunol (2022) 13:863095). Briefly, as previously described, 7 participants (7 PV) in cohort 3 were treated for 15 weeks and 15 participants (8 PV, 7 PF) in cohort 4 were treated for 34 weeks (Goebeler M et al. Br J Dermatol (2021) 186(3):429-39). PV or PF diagnosis was confirmed by positive direct immunofluorescence and positive indirect immunofluorescence and / or Dsg-1 / 3 ELISA. Participants were newly diagnosed or relapsed, with disease severity mild to moderate (pemphigus disease area index [PDAI] < 45 at baseline). Before the treatment period, the screening period was up to 3 weeks and then followed by a 10-week treatment-free follow-up period. In cohort 3, intravenous (IV) efgartigimod was administered at 10 mg / kg weekly for 4 weeks as an induction period, followed by once every other week for 12 weeks as a maintenance period. In cohort 3, efgartigimod could be started as monotherapy or in combination with prednisone at 20 mg / day, at the discretion of the investigator, and could be tapered starting from the maintenance period. In cohort 4, IV efgartigimod was administered at 25 mg / kg of body weight weekly until end of control (EoC), defined as the time when no new lesions had appeared for at least 2 weeks and most (i.e., approximately 80% of the identified lesions had healed). Thereafter, participants were dosed once every other week. In cohort 4, efgartigimod was started with prednisone (20 mg / day) in all newly diagnosed participants and relapsed participants who had discontinued treatment, or at a tapered dose at the time of relapse. The oral prednisone dose could be tapered starting at EoC. During the study period, other systemic treatments for pemphigus were not allowed, but topical corticosteroids, analgesics, and supportive care for corticosteroid treatment (e.g., vitamin D, proton-pump inhibitors, and specific diets) were permitted.

[0306] The inhibitory effect of CIC was measured in six PV participants, and six participants in PF received extended efgartigimod treatment in cohorts 3 and 4 and achieved sustained clinical responses. These participants had IgG CIC analysis by C1q ELISA, which detects complement-fixed IgG antibodies (providing no information on CIC antigen specificity). Briefly, a CIC-C1q EIA kit (A001, Quidel) was used to detect the levels of IgG aggregates associated with C1q in serum at different time points according to the manufacturer's protocol. Calibrators provided by the kit were used to determine the expression levels. IgG CIC levels were considered clinically significant if ≥4.0 mg Eq / ml.

[0307] Four participants showed elevated baseline CIC levels, but a significant decrease in CIC was observed during efgartigimod treatment ( Figure 1 ), consistent with the observed improvement in clinical condition. This suggests that efgartigimod treatment reduces CIC in pemphigus patients.

[0308] Example 2: Study of the Efficacy and Safety of Efgartigimod in Chinese Patients with Lupus Nephritis (LN)

[0309] Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disease. LN is an inflammatory autoimmune disease of the kidneys caused by SLE and is the most common life-threatening manifestation of SLE.

[0310] Among unselected SLE patients, approximately 25% to 50% have signs or symptoms of kidney disease at the onset of SLE, and during the course of the disease, approximately 40% to 60% of SLE patients will develop kidney damage. In China, approximately half of SLE patients have kidney damage.

[0311] In active proliferative LN, current recommendations for induction therapy are mycophenolate mofetil (MMF) or mycophenolic acid (MPA) or low-dose intravenous (IV) cyclophosphamide (CYC), all used in combination with glucocorticoids. 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, in LN patients, 10% to 30% of patients will develop end-stage renal disease (ESRD), which is the ultimate manifestation of LN. In addition, up to 60% of patients are unable to achieve treatment goals with currently available treatment options.

[0312] The neonatal Fc receptor (FcRn) maintains the constant level of IgG in serum by rescuing IgG antibodies from lysosomal degradation after absorption into cells. Given the mechanism of action of efgartigimod in reducing IgG levels, efgartigimod may benefit patients with LN. In addition, efgartigimod has been shown to reduce circulating immune complexes in patients with pemphigus (Example 1; Figure 1 ). Since LN is mainly caused by the renal deposition of immune complexes, this provides further proof of concept for the treatment and / or prevention of LN attacks or progression with efgartigimod.

[0313] A. Study design

[0314] Overall Design

[0315] This was a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of efgartigimod IV in Chinese patients with active LN.

[0316] The study included a screening period of up to 4 weeks, a treatment period of 24 weeks, and a follow-up period of 8 weeks.

[0317] Approximately 60 participants who met the eligibility criteria during the screening period were randomly assigned in a 1:1 ratio to receive weekly infusions of efgartigimod IV or placebo, both administered in combination with standard of care (SoC; i.e., glucocorticoids and MMF / MPA) for 24 weeks. Randomization was stratified according to the LN renal biopsy class (class III / IV with V or class III / IV without V).

[0318] The primary endpoint was week 24 of change from baseline to UPCR. Secondary endpoints included additional efficacy endpoints, PK, PD, immunogenicity, biomarkers, safety, and quality of life (see Table S6).

[0319] One week after receiving the last infusion of the investigational medicinal product (IMP) (week 24), eligible participants could choose to enter an optional open-label follow-up study aimed at evaluating the long-term safety of efgartigimod in this patient population. Participants who did not participate in the open-label follow-up study remained in the main study for 8 weeks of safety follow-up.

[0320] The Data Safety Monitoring Board (DSMB) will review all unblinded safety data, including IgG levels during the study.

[0321] Selection of Primary Endpoints

[0322] A large body of evidence indicates that early reduction of proteinuria, especially within 6 to 12 months from the start of treatment, is the best predictor of improved long-term outcomes, including reduced risk of disease exacerbation, ESRD, and death. Therefore, proteinuria or UPCR is a useful parameter for assessing treatment efficacy and is a preferred prognostic indicator for regulatory agencies.

[0323] Early reduction of UPCR indicates long-term benefits of LN treatment, which supports its use as the primary endpoint of this study.

[0324] Rationale for Placebo Control

[0325] The design of this placebo-controlled study is acceptable for this patient population because SoC (immunosuppression with glucocorticoids and MMF / MPA) was administered in addition to placebo. A placebo-controlled study that does not include SoC for LN patients would represent under-treatment of a population at risk of severe kidney damage and potential ESRD.

[0326] Dose Adjustment

[0327] Based on the results of previous clinical studies, including a phase 3 study in patients with generalized myasthenia gravis (gMG), administration of efgartigimod IV 10 mg / kg q7d as 4 infusions achieved near-maximal total IgG reduction, which led to a reduction in pathogenic autoantibodies and was associated with clinical efficacy in gMG patients. In addition, this dose was well tolerated, and there were no safety concerns in all populations tested to date.

[0328] LN patients may have a certain degree of renal impairment and / or nephrotic proteinuria. The molecular weight of efgartigimod is approximately 54 kDa and is thus at the boundary of molecules filtered by the kidney. After a single dose of efgartigimod IV 10 mg / kg in healthy subjects, less than 0.1% of the administered dose was recovered in urine. A population covariate analysis approach was used to evaluate the potential impact of eGFR as a marker of renal function on the PK profile of efgartigimod. A statistically significant decrease in clearance was identified with decreasing eGFR, resulting in increased exposure. However, healthy volunteers tolerated multiple IV doses up to 25 mg / kg well. Therefore, a weekly dose of 10 mg / kg IV was selected for this study to achieve the maximum pharmacodynamic (IgG reduction) effect in this population.

[0329] B. Study Population

[0330] Prospective approval of protocol deviations to the recruitment and inclusion criteria, also known as protocol waivers or exemptions, is not permitted.

[0331] Inclusion Criteria

[0332] Participants are eligible for inclusion in the study only if all of the following criteria are met:

[0333] - At least 18 years old at the time of signing the informed consent form;

[0334] - Able to sign the informed consent form, which includes complying with the requirements and restrictions listed in the informed consent form and this agreement;

[0335] - Diagnosed with SLE according to the Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria;

[0336] - Active, proliferative class III or IV LN [excluding classes III(C), IV-S(C) and IV-G(C)], with or without class V, as demonstrated by renal biopsy within 6 months before randomization and confirmed by the central biopsy reading group, using the 2003 International Society of Nephrology (ISN) / Renal Pathology Society (RPS) criteria;

[0337] - Requiring LN induction therapy (glucocorticoids and MMF / MPA) according to the investigator's clinical judgment. Induction therapy may be started before screening but should be started within 60 days before randomization;

[0338] - At screening, positive anti-nuclear antibody (ANA) test result defined by ANA titer ≥ 1:80 (equivalence based on Hep-2 immunofluorescence assay or enzyme immunoassay)

[0339] ;

[0340] - At screening, at least one of the following criteria is met:

[0341] a. Elevated anti-dsDNA (≥ 30 IU / mL),

[0342] b. Low complement levels (C3 < 0.9 g / L or C4 < 0.1 g / L);

[0343] - At screening, urine protein creatinine ratio (UPCR) ≥ 1.0 mg / mg;

[0344] - At screening, estimated glomerular filtration rate (eGFR) ≥ 60 mL / min / 1.73m 2 ;

[0345] - Serum total IgG ≥ 6 g / L at screening. The eligibility of participants with total IgG between 4 and 6 g / L at screening needs to be discussed on a case-by-case basis with the sponsor's medical monitor;

[0346] - Contraceptive measures for non - sterilized male participants and women of child - bearing potential (WOCBP) comply with local regulations (if any) for individuals participating in clinical research. WOCBP must have a negative serum pregnancy test during screening and a negative urine pregnancy test at baseline to confirm non - pregnancy status prior to receiving the investigational medicinal product (IMP).

[0347] Exclusion Criteria

[0348] Participants are excluded from the study if they meet any of the following criteria:

[0349] - Active or chronic infections requiring treatment:

[0350] a. Currently receiving any therapy for chronic infections, including but not limited to tuberculosis, pneumovirus, cytomegalovirus, herpes simplex virus, herpes zoster or atypical mycobacteria,

[0351] b. Any type of active infection (excluding onychomycosis) within 60 days prior to randomization or any major infection episode requiring hospitalization or parenteral (IV or intramuscular) antibiotic treatment (e.g., antibacterial, antiviral, antifungal or antiparasitic medications) or oral antibiotics within 2 weeks prior to randomization;

[0352] - Any evidence of central nervous system (CNS) lupus (including but not limited to seizures, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis or CNS vasculitis);

[0353] - Currently receiving renal dialysis or expected to require dialysis during the study;

[0354] - Previous kidney transplantation or planned transplantation during the study;

[0355] - History of malignancy, unless considered cured by adequate treatment and without signs of recurrence for ≥ 3 years prior to randomization. The following cancers are not exclusive:

[0356] a. Basal cell or squamous cell skin cancer that has been adequately treated,

[0357] b. Carcinoma in situ of the cervix,

[0358] c. Carcinoma in situ of the breast,

[0359] d. Incidental histological finding of prostate cancer (TNM stage T1a or T1b);

[0360] - Heart failure (New York Heart Association [NYHA] class III or IV) due to SLE or any other severe cardiovascular involvement, as judged by the investigator and posing a safety concern;

[0361] - Any other known autoimmune disease that the investigator believes would interfere with the accurate assessment of the clinical symptoms of SLE / LN or place the participant at undue risk;

[0362] - Clinical evidence of other major or uncontrolled serious diseases (i.e., cardiovascular, pulmonary, hematological, gastrointestinal, hepatic, renal, or neurological), recent major surgery, or any other condition that the investigator believes may confound the study results or place the participant at inappropriate risk;

[0363] - Previous treatment failure with MMF or any form of mycophenolate mofetil-based induction therapy, based on the investigator's opinion;

[0364] - Systemic use of glucocorticoid therapy for chronic diseases other than SLE (e.g., asthma, Crohn's disease) within 12 months prior to randomization;

[0365] - Use of any monoclonal antibody within 3 months prior to randomization;

[0366] - Previous treatment with plasma exchange within 3 months prior to randomization;

[0367] - Receipt of CYC and / or CNI within 2 months prior to randomization;

[0368] - Receipt of intravenous immunoglobulin (IVIg) within 4 weeks prior to randomization;

[0369] - Use of complementary therapies, including traditional Chinese medicine, herbal medicine, or procedures (e.g., acupuncture), within 4 weeks prior to randomization that may interfere with the efficacy and safety of the participant as evaluated by the investigator;

[0370] - Receipt of live / attenuated vaccines within 28 days prior to randomization. Receipt of any inactivated, subunit, polysaccharide, or conjugate vaccine at any time prior to screening is not considered excludable. Participants are advised to be up-to-date on vaccinations prior to the first dose of IMP;

[0371] - Previous participation in a clinical study of efgartigimod;

[0372] - Use of any investigational therapy within 3 months or 5 half-lives (whichever is longer) prior to randomization;

[0373] - Screening positive for serum tests for active viral infections under any of the following conditions:

[0374] a. Hepatitis B virus (HBV) indicating acute or chronic infection, unless associated with a negative HBV DNA test according to the recommendations of the Centers for Disease Control and Prevention,

[0375] b. Hepatitis C virus (HCV) based on HCV antibody assay, unless associated with an HCV-negative RNA test,

[0376] c. HIV based on association with any of the following test results:

[0377] (1) AIDS-defining illness or CD4 count < 200 cells / mm 3 ,

[0378] (2) Inadequate antiretroviral therapy;

[0379] - Positive SARS-CoV-2 antigen-based test at screening. Testing is required regardless of whether the participant has been vaccinated;

[0380] - Serum total IgG < 4 g / L at screening;

[0381] - Evidence of unstable kidney function defined as a > 20% decrease in eGFR within 3 months prior to randomization;

[0382] - Having any of the following laboratory test values at screening:

[0383] a. Alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST) > 3 times the upper limit of normal (ULN),

[0384] b. Total bilirubin > 1.5 × ULN,

[0385] c. Platelets < 75 × 10 9 / L,

[0386] d. Neutrophils < 1.5 × 10 9 / L,

[0387] e. Hemoglobin < 8 g / dL;

[0388] - Known allergy or contraindication to any excipient of efgartigimod, IMP, or the SoC used in the study;

[0389] - Current or historical (i.e., within 12 months of randomization) alcohol, drug, or substance abuse in the opinion of the investigator;

[0390] - Pregnant or lactating women and women intending to become pregnant during the study participation;

[0391] - Any condition or circumstance that, in the opinion of the investigator, renders the participant ineligible for the study.

[0392] C. IMP and concomitant therapies

[0393] An Investigational Medicinal Product (IMP) is defined as any investigational intervention, marketed product, placebo, or medical device intended to be administered to study participants according to a study protocol.

[0394] IMP Administered

[0395] The IMPs in this study included efgartigimod IV and a matched placebo (with the same formulation but without the active ingredient of efgartigimod), as described in Table S1:

[0396] Table S1. IMPs Administered

[0397]

[0398] Any medications or vaccines (including over-the-counter or prescription drugs, vitamins, and / or herbal supplements) received by participants within 30 days after signing the Informed Consent Form (ICF) or during their participation in the study must be recorded.

[0399] In addition, the vaccination history of participants within the 12 months prior to signing the ICF was recorded, including any vaccinations against COVID-19. The brand name of the vaccine and the vaccination date were also recorded if known.

[0400] For any questions regarding concomitant or prior treatments, the sponsor's medical monitor should be contacted.

[0401] All participants received glucocorticoids as part of the LN induction therapy (see inclusion criteria). A combination of IV and oral glucocorticoids was permitted, and the initial IV pulse / bolus of methylprednisolone was completed prior to randomization. The dose of IV methylprednisolone for each participant will be determined based on the participant's clinical condition; a specified dose (250 mg to 500 mg / day for up to 3 days, with flexible dosing according to the severity of the disease) is provided as a reference.

[0402] All participants must receive oral prednisone at an equivalent dose of ≥10 mg / day but ≤60 mg / day (or 1.0 mg / kg / day, whichever is lower) at the time of randomization. The glucocorticoid tapering regimen is specified by the protocol and is described below.

[0403] After the use of IV methylprednisolone, an initial oral prednisone dose of 0.5 to 1.0 mg / kg / day but not exceeding 60 mg / day is recommended. The calculated dose is rounded to the nearest 10-mg increment listed in Table S2. Participants are instructed to start glucocorticoid tapering 2 weeks after starting oral glucocorticoids according to the schedule listed in Table S2.

[0404] Table S2. Prednisone Dose Tapering Schedule

[0405]

[0406] For LN exacerbation, participants were optionally treated with prednisone (0.5 to 1.0 mg / kg / day, but ≤60 mg / day) for 2 weeks and then tapered to ≤10 mg / day within 6 weeks after the initial corticosteroid increase (see Table S3).

[0407] Table S3. Prednisone dose recommendations for LN exacerbation

[0408]

[0409] For extra-renal exacerbation, depending on the severity of the disease, participants could choose to be treated with prednisone up to 1.0 mg / kg / day (not exceeding 60 mg / day) and follow the tapering schedule recommended in Table S4. Intravenous equivalent doses of corticosteroids were allowed if gastrointestinal involvement temporarily precluded oral use of corticosteroids.

[0410] Table S4. Prednisone dose recommendations for extra-renal exacerbation

[0411]

[0412] All participants continued treatment with MMF (or MPA) started during screening, which was part of the LN induction therapy. Within 4 weeks, the MMF was titrated in divided doses to a maximum of 1.5 g to 2 g / day (or equivalent dose).

[0413] Participants who started LN induction therapy ≥60 days before randomization were ineligible unless the previous induction was completed or terminated ≥2 months before randomization and re-induction was deemed necessary by the investigator.

[0414] For participants taking angiotensin-converting enzyme inhibitor (ACEi) / angiotensin receptor blocker (ARB), the dose of ACEi and / or ARB should be kept stable throughout the treatment period.

[0415] All participants were strongly recommended to receive hydroxychloroquine (maximum dose 5 mg / kg / day) at screening / baseline visit and during treatment. The dose of hydroxychloroquine was kept stable unless a change was required.

[0416] Bacterial prophylaxis was initiated, at the discretion of the investigator, in selected participants considered to be at high risk of developing infection either at randomization or at any time during the study.

[0417] If renal function deteriorated (LN exacerbation) during treatment, at the discretion of the investigator, the salvage therapy was as follows:

[0418] ·A reduction in eGFR of >20% from baseline (confirmed by repeat testing), accompanied by at least 1 of the following: 24-hour and / or spot UPCR >1.0 mg / mg, red blood cell casts, or white blood cell casts; and / or

[0419] ·An increase in 24-hour UPCR:

[0420] - If baseline UPCR < 3.5 mg / mg, increase 24-hour UPCR to ≥ 3.5 mg / mg and an increase in 24-hour UPCR greater than twice the baseline value (confirmed by repeat testing or spot UPCR within 2 weeks),

[0421] - If baseline UPCR ≥ 3.5 mg / mg, an increase in 24-hour UPCR greater than twice the baseline value (confirmed by repeat testing or spot UPCR within 2 weeks).

[0422] In these cases, the investigator may increase the glucocorticoid dose. Participants receive oral glucocorticoid treatment with prednisone at a dose of 0.5 to 1.0 mg / kg / day, but ≤ 60 mg / day, for up to 2 weeks, followed by a gradual taper of prednisone to a dose of ≤ 10 mg / day within 6 weeks after starting the taper. Further tapering is at the discretion of the investigator. Participants who do not respond to the initial 2-week course of glucocorticoid increase and then start new immunosuppressive therapy (prohibited drugs as defined in this study) are considered treatment failures.

[0423] If a participant is at risk of or has an immediate risk of developing a severe lupus clinical situation (including but not limited to lupus encephalopathy, pulmonary hemorrhage, and lupus crisis), the participant will stop the IMP or withdraw from the study at any time and receive clinically appropriate individualized treatment in the best interest of the participant as determined by the investigator.

[0424] Participants who experience an exacerbation of extra-renal SLE during treatment optionally receive salvage treatment with additional oral glucocorticoids. An exacerbation of extra-renal SLE is defined as an increase in the SLEDAI-2K score that is not explained by hypocomplementemia, or an increase in anti-dsDNA antibody levels, or the initiation of new immunosuppressive therapy or an increase in corticosteroids (if the investigator determines that it is clinically appropriate). The investigator should inform the sponsor's medical monitor about the clinical interventions for the exacerbation. Based on the severity of the disease and organ system, at the discretion of the investigator, these participants are optionally treated with prednisone (up to 1.0 mg / kg / day, but ≤ 60 mg / day) for 2 weeks; and then gradually tapered to ≤ 10 mg / day following a separate tapering schedule. If a participant requires new immunosuppressive therapy (other than glucocorticoids) to treat an exacerbation of extra-renal SLE, these participants are considered treatment failures.

[0425] Before initiating salvage glucocorticoid therapy, if possible, at the time of determining increased disease activity, complete all evaluations related to the visit. If increased disease activity is determined between scheduled visits, the participant will return to the clinic, along with all evaluations for unscheduled visits listed due to increased lupus activity, including:

[0426] · A 24-hour UPCR urine collection;

[0427] · Point-of-care UPCR;

[0428] · SLEDAI-2K assessment;

[0429] · Hematology, clinical chemistry, and urinalysis;

[0430] · Vital signs and physical examination (optionally, a brief physical examination at the discretion of the investigator based on the participant's condition); Collection of blood samples for PK, PD, and immunogenicity (if applicable and possible);

[0431] · Collection of blood samples for biomarkers (if applicable and possible);

[0432] · Other evaluations at the discretion of the investigator.

[0433] Participants initiating salvage therapy continue IMP administration according to Table S5 or until the criteria for stopping IMP are met.

[0434] If clinically warranted, participants are allowed to receive corticosteroids for acute illness (e.g., trauma, severe asthma) or surgery. Corticosteroids are administered to participants at the discretion of the investigator to treat symptoms of adrenal insufficiency or steroid withdrawal. However, in these cases, other corticosteroids should not exceed 2.5 mg / day for more than 7 days. If surgery is required, instruct the participant to notify the relevant clinical staff that they are participating in a clinical study where high-dose steroids are not permitted. If possible, provide the investigator with detailed surgical and anesthesia reports for review. These reports are kept in the participant's medical record to document concomitant medications / therapies.

[0435] Prohibited Medications

[0436] The following medications / treatments are prohibited:

[0437] · Investigational therapies within 3 months or 5 half-lives (whichever is longer) before randomization and during the treatment period;

[0438] · Any monoclonal antibody treatment within 3 months before randomization and during the treatment period;

[0439] · CYC within 2 months before randomization and during treatment;

[0440] · CNI within 2 months before randomization and during treatment;

[0441] · Adjuvant therapies, including traditional Chinese medicine, herbal medicine, or procedures (e.g., acupuncture), that the investigator assesses may affect the efficacy and safety of the participants within 4 weeks before randomization and during treatment;

[0442] · Live / attenuated vaccines within 28 days before randomization and during treatment;

[0443] · Other immunosuppressants are not explicitly permitted in the study during the study period.

[0444] Restrictions on Concomitant Medications

[0445] The following are the restrictions on concomitant medications:

[0446] · MMF at a specified dose greater than 3 g / day at baseline and during treatment, or MPA at a specified dose greater than 2160 mg / day;

[0447] · Initiate ACEi / ARB treatment during treatment;

[0448] · Initiate antimalarial treatment during treatment;

[0449] · IV glucocorticoids for LN during treatment;

[0450]

[0451]

[0452] b For participants who received at least 1 dose of IMP and withdrew from the study (except for withdrawal of consent), the evaluations listed in the ED visit were completed within 1 week after receiving the final IMP dose. A safety follow-up visit (such as V29) was also conducted 9 weeks (±3 days) after receiving the final IMP dose.

[0453] c If the disease activity increases or for safety reasons, the participant can come to the study site for a UNS visit.

[0454] d A renal biopsy is required within 6 months before randomization. The diagnosis and class of LN must be confirmed by the central biopsy reading group.

[0455] e Screening tests are performed at local or central laboratories.

[0456] fThe tests are conducted at local or central laboratories. Results obtained within 28 days prior to screening are acceptable.

[0457] g At screening, a positive PCR test for SARS-CoV-2 is an exclusivity for study participation. Nasal and / or throat mucosal cell samples are collected using the on-site guidelines. Samples are tested for SARS-CoV-2 according to national and / or on-site level regulations and / or requirements.

[0458] h At screening, WOCBP undergoes a serum pregnancy test. Serum or urine pregnancy tests are used at other visits. Screening and V2 pregnancy test results must be available before randomization of the participant.

[0459] i FSH levels within the postmenopausal range are used to confirm the postmenopausal status of women; for women on hormonal therapy in the postmenopausal state, the postmenopausal status is evaluated by the investigator. The tests are conducted at local or central laboratories.

[0460] j CH50, C3, C4, anti-dsDNA, ANA, and C1q-binding circulating immune complexes are analyzed at the central laboratory and evaluated as biomarkers.

[0461] k Participants collect 1×24-hour urine samples and hand them over to on-site staff during outpatient visits. Sample collection must start within 2 days before each visit V7, V15, and ED visit (if applicable). Analysis of urine samples is conducted at the central laboratory.

[0462] l Participants collect 2 consecutive (7 to 14 days apart) 24-hour V2 and V27 urine samples and hand them over to on-site staff during outpatient visits. The second sample collection must start within 2 days before each visit. Analysis of urine samples is conducted at the central laboratory.

[0463] m Participants provide urine samples for on-site UPCR testing. Analysis of urine samples is conducted at the central laboratory.

[0464] n Hematological parameters include RBC count, platelet count, hemoglobin, and hematocrit. RBC indices of MCV, MCH, and MCHC are obtained. Differential (%) and absolute numbers of WBC count are obtained for neutrophils, eosinophils, lymphocytes, basophils, and monocytes. The tests are conducted at local or central laboratories. For V2, results obtained within 7 days before V2 are acceptable.

[0465] o Samples are collected after fasting for at least 8 hours (no food or drink except water). Clinical chemistry parameters include ALT, AST, ALP, lactate dehydrogenase, GGT, total protein albumin, uric acid, blood urea / BUN, total cholesterol, HDL / HDL-C, LDL / LDL-C, triglycerides, total bilirubin and direct bilirubin, glucose, creatinine, creatine kinase, potassium, sodium, calcium, and chloride. Screening tests are performed in local or central laboratories; tests for other scheduled visits and ED visits (if applicable) are performed in the central laboratory. For V2, central laboratory results obtained within 7 days prior to V2 can be used.

[0466] p Urinalysis parameters include specific gravity, pH, glucose, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes, urinary casts, and microscopic examination of RBC count and WBC count. Screening tests are performed in local or central laboratories; tests for other scheduled visits and ED visits (if applicable) are performed in the central laboratory. For V2, central laboratory results obtained within 7 days prior to V2 can be used.

[0467] q Vital sign parameters include blood pressure (systolic and diastolic), pulse rate, respiratory rate, and body temperature. Participants must rest in a quiet environment for at least 5 minutes before measurement. Blood pressure and pulse rate are measured in the seated position. Vital signs are measured during the visit for administration of IMP, before and after IMP infusion.

[0468] r A complete physical examination includes the following assessments: general appearance, respiratory tract, cardiovascular, abdomen, skin, head and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid gland, musculoskeletal (including spine and limbs), and nervous system. A complete physical examination is performed for screening, V2, and V27; for other visits, the investigator performs a brief physical examination at their discretion based on the participant's condition.

[0469] s PK samples at V2 are collected at the end of the infusion, 1 hour before the pre-dose (EOI; ±5 minutes), and 4 hours after the infusion (±30 minutes); and at V7 and V15 within 1 hour of the pre-dose and at EOI (±5 minutes).

[0470] t PD parameters include total IgG level.

[0471] u Blood samples for immunogenicity assessment of ADA against efgartigimod are determined. Immunogenicity samples collected at screening are only used for verification purposes

[0472] v Biomarkers include anti-dsDNA, ANA, aCL, anti-Sm, anti-C1q, C3, C4, CH50, and C1q-binding circulating immune complexes.

[0473] w Body weight was measured in participants wearing light clothing and no shoes. Height was measured without shoes at V2. During treatment, body weight was measured before each IMP administration. Dose was calculated based on the participant's baseline (V2, Day 1) body weight, but was recalculated for significant changes in body weight (> 10% compared to baseline).

[0474] x The first dose was administered on Day 1. IMP was administered once weekly as an intravenous infusion for 1 hour. Participants were observed for at least 30 minutes after the end of the infusion for routine safety monitoring.

[0475] Urine Protein Creatinine Ratio (UPCR)

[0476] UPCR (in mg / mg) was measured on 24-hour, 2 x 24-hour, and spot urine samples. See Table S5 for the timing and instructions for urine sample collection. Instructions on the procedure for collecting 24-hour urine samples at home were provided to participants. Parameters included:

[0477] · Proteinuria;

[0478] · Urine creatinine;

[0479] · UPCR.

[0480] SLEDAI-2K Assessment

[0481] The SLEDAI-2K instrument was used to assess disease activity in SLE (see Table S5). The results of the following assessments were required for a complete SLEDAI-2K assessment:

[0482] · Proteinuria (based on 24-hour urine collection);

[0483] · Platelets and white blood cells;

[0484] · Urinary casts, microscopic examination of red blood cell count, and white blood cell count in urine;

[0485] · Body temperature;

[0486] · Anti-dsDNA, C3, C4, and CH50.

[0487] Circulating Immune Complex (CIC) Assessment

[0488] Collect blood samples according to the schedule described in Table S5, which is detailed in the laboratory manual provided at the study site. Determine the CIC level using a validated method.

[0489] Definition of Clinical Outcome

[0490] The complete renal response (CRR) is defined as:

[0491] · eGFR ≥ 60 mL / min / 1.73m 2 or no confirmed baseline eGFR value > 20%,

[0492] and

[0493] · UPCR ≤ 0.5 mg / mg,

[0494] and

[0495] · The criteria for treatment failure are not met.

[0496] The modified complete renal response (mCRR) is defined as:

[0497] · eGFR ≥ 90 mL / min / 1.73m 2 or no confirmed baseline eGFR value > 10%,

[0498] and

[0499] · UPCR ≤ 0.5 mg / mg,

[0500] and

[0501] · The criteria for treatment failure are not met.

[0502] The partial renal response (PRR) is defined as:

[0503] · eGFR ≥ 60 mL / min / 1.73m 2 or no confirmed baseline eGFR value > 20%,

[0504] and

[0505] · UPCR is reduced by ≥ 50% from baseline, meeting one of the following conditions:

[0506] - If baseline UPCR ≤ 3.0 mg / mg, then UPCR < 1.0 mg / mg,

[0507] - If baseline UPCR > 3.0 mg / mg, then UPCR < 3.0 mg / mg,

[0508] and

[0509] · The criteria for treatment failure are not met.

[0510] Treatment failure is defined as:

[0511] · By week 24, the dose of glucocorticoid > 10 mg / day of prednisone,

[0512] or

[0513] · During treatment, received any of the following prohibited drugs or restricted concomitant medications:

[0514] - The specified dose of MMF > 3 g / day, or the specified dose of MPA > 2160 mg / day,

[0515] - Initiated a new immunosuppressive therapy for LN, including but not limited to CYC, CNI, rituximab, etc.,

[0516] - IV glucocorticoids for LN.

[0517] E. Pharmacokinetics

[0518] Blood samples for PK analysis were collected at the time points described in Table S5. The serum concentration of efgartigimod was determined using a validated method.

[0519] F. Pharmacodynamics

[0520] Blood samples for PD assessment to determine the total IgG level in serum were collected at the time points described in Table S5. The total IgG level was determined using a validated method.

[0521] G. Biomarkers

[0522] Blood samples for biomarker studies were collected according to the schedule described in Table S5 and are detailed in the laboratory manual provided at the study site.

[0523] Biomarkers include:

[0524] · Autoantibodies (anti-dsDNA, ANA, aCL, anti-Sm, and anti-C1q),

[0525] · Complement (C3, C4, CH50, and C1q-binding circulating immune complexes).

[0526] H. Immunogenicity assessment

[0527] Blood samples were collected at the time points described in Table S5 to assess the serum level of ADA against efgartigimod.

[0528] Analyze the samples through a designated laboratory using a validated immunogenicity assay. Initially, screen the samples to generate a positive assay response (Tier 1). Then, test the screened positive samples in a confirmatory assay (Tier 2). Finally, titrate the ADA response in the positive Tier 2 samples to characterize the magnitude of the antibody response (Tier 3).

[0529] I. Health economics or healthcare resource utilization and health economics

[0530] Participants complete a health-related quality of life questionnaire (EQ-5D-5L) at the pre-specified time points shown in Table S5.

[0531] The EQ-5D-5L questionnaire is a standardized test recognized by many health authorities as a generic measure of health status for clinical and economic evaluation. The descriptive system includes 5 dimensions: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. The scores for each dimension include 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems.

[0532] The EQ-5D-5L includes a visual analogue scale (VAS). Participants mark their health status on a scale from 0 (the worst health you can imagine) to 100 (the best health you can imagine).

[0533] J. Objectives and endpoints

[0534] Table S6. Objectives and endpoints

[0535]

[0536]

[0537] ***

[0538] The scope of the present invention is not limited to the specific embodiments described herein. Indeed, various modifications of the present invention will become apparent to those skilled in the art in light of the foregoing description and drawings. Such modifications are intended to fall within the scope of the appended claims.

Claims

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

2. The method according to claim 1, wherein the FcRn antagonist comprises two, three or four FcRn binding domains.

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

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

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

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

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

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

9. The method according to any one of claims 6 to 8, wherein the first Fc domain and / or the second Fc domain comprises 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. The method according to any one of claims 6 to 9, wherein the first Fc domain and the second Fc domain comprises 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.

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

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

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

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

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

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

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

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

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

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

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

23. The method according to any one of claims 1 to 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. The method according to claim 23, wherein the glucocorticoid is methylprednisolone.

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

26. The method according to claim 23 or 24, wherein the methylprednisolone is administered for 1 to 3 days per day.

27. The method according to any one of claims 24 to 26, wherein the methylprednisolone is administered for 3 days.

28. The method according to claim 23, wherein the glucocorticoid is prednisone.

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

30. The method according to 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. The method according to any one of claims 28 or 30, wherein when the subject is administered the FcRn antagonist, the dose of prednisone is gradually reduced to a dose of 7.5 mg / day within 12 weeks.

32. The method according to claim 23, wherein the MMF or MPA is administered daily.

33. The method according to claim 32, wherein the MMF or MPA is administered in a daily dose, and the daily dose is gradually increased to 1.5 g / day to 2 g / day in divided doses over 4 weeks.

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

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

36. The method according to claims 34 to 35, wherein the hydroxychloroquine is administered for at least 24 weeks.

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

38. A method of treating a subject in need thereof for lupus nephritis, the method 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. The method according to claim 38, wherein the induction therapy comprises administering to the subject an effective amount of a glucocorticoid.

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

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

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

43. The method according to any one of claims 40 to 42, wherein the methylprednisolone is administered for 3 days.

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

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

46. The method according to 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. The method according to any one of claims 44 or 46, wherein when the subject is administered the FcRn antagonist, the dose of prednisone is gradually reduced to a dose of 7.5 mg / day over 12 weeks.

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

49. The method according to claim 48, wherein the daily dose of MMF or MPA is gradually increased to 1.5 g / day to 2 g / day in divided doses over 4 weeks.

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

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

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

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

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

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

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

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

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

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

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

62. The method according to any one of claims 1 to 61, wherein 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.

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

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

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

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

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

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

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

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

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

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

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

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

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

76. The method according to 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 lower compared to the baseline level of serum IgG obtained from the subject before administering the FcRn antagonist.

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

79. The method according to any one of claims 1 to 78, wherein after administration of the FcRn antagonist to the 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 prior to administration of the FcRn antagonist.

80. The method according to any one of the foregoing 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. The method according to claim 80, wherein the aqueous solution comprises about 3.2 mg / ml of the FcRn antagonist.

82. The method according to any one of claims 1 to 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. The method according to claim 82, wherein the aqueous solution comprises about 180 mg / ml of the FcRn antagonist.

84. The method according to any one of claims 1 to 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. The method according to claim 84, wherein the aqueous solution comprises about 200 mg / ml of the FcRn antagonist.

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

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

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

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

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