Methods of improving anti-fcRn therapy

Abstract

This disclosure describes a method for improving anti-FcRn therapy (e.g., anti-FcRn antibody dosing regimen) for treating autoimmune diseases (e.g., Graves' disease (GD), thyroid ophthalmopathy (TED), rheumatoid arthritis (RA), myasthenia gravis (MG), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), etc.).

Description

[0001] Related applications

[0002] This application claims priority to U.S. Provisional Application No. 63 / 594,708, filed October 31, 2023, and U.S. Provisional Application No. 63 / 603,009, filed November 27, 2023, the entire contents of which are incorporated herein by reference.

[0003] Reference to electronic sequence listing

[0004] The contents of the electronic serial number (I062870008WO00-SEQ-LJG.xml; size: 22,486 bytes; and creation date: October 29, 2024) are incorporated herein by reference in full. Technical Field

[0005] This disclosure relates to methods for improving anti-FcRn therapy. Background Technology

[0006] The neonatal Fc receptor (FcRn) is a non-covalent heterodimer normally found in endosomes of endothelial and epithelial cells. FcRn is a membrane-bound receptor with three heavy chain α regions (α1, α2, and α3) and a single soluble light chain β2-microglobulin (β2m) region. Structurally, it belongs to the major histocompatibility complex (MHC) family of molecules with β2m as a common light chain. The FcRn chain has a molecular weight of approximately 46 kDa and consists of an extracellular region containing α1, α2, and α3 heavy chain regions and a β2m light chain region with a single sugar chain, a single transmembrane region, and a relatively short cytoplasmic tail region.

[0007] Antibodies and other therapies targeting FcRn are being developed for the treatment of autoimmune diseases. Summary of the Invention

[0008] The neonatal Fc receptor (FcRn) regulates the half-life of IgG antibodies by binding to the Fc region and albumin in the body. FcRn prolongs the half-life of IgG by protecting it from lysosomal degradation during Fc binding and immunoglobulin internalization. FcRn-Fc interactions are beneficial in promoting long-term protection against pathogens or in response to vaccination; however, in antibody-mediated diseases such as autoimmune diseases, FcRn function may exacerbate the disease state by prolonging the half-life of autoantibodies. Therefore, anti-FcRn therapy can treat or improve antibody-driven autoimmune diseases such as Graves' disease, thyroid ophthalmopathy (TED), rheumatoid arthritis (RA), myasthenia gravis (MG), immune thrombocytopenic purpura, pemphigus vulgaris, chronic inflammatory demyelinating polyneuropathy (CIDP), systemic lupus erythematosus (SLE), and other diseases. However, due to the chronic and periodic nature of many autoimmune symptoms (e.g., with remission and flare-up phases) and the pharmacokinetics of different anti-FcRn therapies, determining the appropriate amount, frequency, and duration of administration for adequate treatment is challenging.

[0009] In one aspect, this document provides a method for treating an autoimmune disease in a subject of need, the method comprising administering to the subject a loading dose, an induction dose, and a maintenance dose of an anti-FcRn therapy. In some embodiments, the method comprises administering the induction dose for 12 weeks. In some embodiments, the method comprises administering the maintenance dose for 12 weeks. In some embodiments, the method comprises administering the maintenance dose for 12 months. In some embodiments, the method comprises administering the loading dose on day 4 of the first week of the induction dose. In some embodiments, the method comprises administering the loading dose on days 4 and 11 of the first two weeks of administration of the induction dose.

[0010] In some embodiments, the induction dose comprises 680 mg of batoclimab administered subcutaneously once weekly. In some embodiments, the maintenance dose comprises 340 mg of batoclimab administered subcutaneously once weekly. In some embodiments, the maintenance dose comprises 340 mg of batoclimab administered subcutaneously every other week. In some embodiments, the loading dose comprises a subcutaneous dose of 680 mg of batoclimab.

[0011] In some embodiments, the autoimmune disease is rheumatoid arthritis. In other embodiments, the autoimmune disease is Graves' disease.

[0012] In some embodiments, the induction dose comprises 600 mg of IMVT-1402 administered subcutaneously once weekly. In some embodiments, the maintenance dose comprises 300 mg of IMVT-1402 administered subcutaneously once weekly. In some embodiments, the maintenance dose comprises 300 mg of IMVT-1402 administered subcutaneously every other week. In some embodiments, the loading dose comprises a subcutaneous dose of 600 mg of IMVT-1402.

[0013] In some embodiments, the autoimmune disease is a progressive autoimmune disease. In some embodiments, the autoimmune disease is CIDP. In some embodiments, the autoimmune disease is myasthenia gravis.

[0014] In some respects, this article provides a method for treating an autoimmune disease in a subject of need, comprising: (a) administering 680 mg of battolimab to the subject on day 1; (b) administering 680 mg of battolimab to the subject on day 4; (c) administering 680 mg of battolimab to the subject on day 8; (d) administering 680 mg of battolimab to the subject on day 11; and (e) administering 680 mg of battolimab to the subject once weekly starting from day 15, for a total treatment duration of 12 weeks.

[0015] In some embodiments, the method further includes step (f): administering 340 mg of battolimab to the subject once weekly, starting on day 85, for a total treatment duration of 24 weeks. In some embodiments, the method includes step (g): administering 680 mg of battolimab to the subject once weekly, starting on day 168, for a total treatment duration of 36 weeks. In some embodiments, the method includes subcutaneous administration of battolimab.

[0016] In some embodiments, the method results in a reduction of at least 50% in the level of at least one autoantibody in the subject compared to baseline by 7 days after initial administration. In some embodiments, the method results in a reduction of at least 75% in the level of at least one autoantibody in the subject compared to baseline by 7 days after initial administration. In some embodiments, such methods result in a reduction of at least 85% in the level of at least one autoantibody in the subject compared to baseline by 7 days after initial administration. In some embodiments, the autoantibody is an antibody against AChR, MuSK, LRP4, agrin, Kv1.4 potassium channel, receptor-linked synaptic protein (rapsyn), cortactin, acetylcholinesterase, collagen Q, or collagen XIII.

[0017] In some embodiments, the method results in a reduction of at least 50% in the subject's total IgG level compared to baseline by 7 days after initial administration. In some embodiments, the method results in a reduction of at least 75% in the subject's total IgG level compared to baseline by 7 days after initial administration. In some embodiments, the method results in a reduction of at least 85% in the subject's total IgG level compared to baseline by 7 days after initial administration. In some embodiments, the autoimmune disease is a progressive autoimmune disease. In some embodiments, the autoimmune disease is CIDP. In some embodiments, the autoimmune disease is myasthenia gravis.

[0018] In some aspects, this article provides a method for treating an autoimmune disease in a subject of need, comprising: (a) administering 600 mg IMVT-1402 to the subject on day 1; (b) administering 600 mg IMVT-1402 to the subject on day 4; (c) administering 600 mg IMVT-1402 to the subject on day 8; (d) administering 600 mg IMVT-1402 to the subject on day 11; and administering 600 mg IMVT-1402 to the subject once weekly starting from day 15, for a total treatment duration of 12 weeks.

[0019] In some embodiments, the method further includes step (f): administering 300 mg of IMVT-1402 to the subject once weekly, starting on day 85, for a total treatment duration of 24 weeks. In some embodiments, the method further includes step (g): administering 600 mg of IMVT-1402 to the subject once weekly, starting on day 169, for a total treatment duration of 36 weeks. In some embodiments, the method includes subcutaneous administration of IMVT-1402.

[0020] In some embodiments, the method results in a reduction of at least 50% in the level of at least one autoantibody in the subject compared to baseline by 7 days after initial administration. In some embodiments, the method results in a reduction of at least 75% in the level of at least one autoantibody in the subject compared to baseline by 7 days after initial administration. In some embodiments, the method results in a reduction of at least 85% in the level of at least one autoantibody in the subject compared to baseline by 7 days after initial administration. In some embodiments, the autoantibody is an antibody against AChR, MuSK, LRP4, agglutinin, Kv1.4 potassium channel, receptor-linked synaptic protein, cortical actin, acetylcholinesterase, collagen Q, or collagen XIII.

[0021] In some embodiments, the method results in a reduction of at least 50% in the subject's total IgG level compared to baseline by 7 days after initial administration. In some embodiments, the method results in a reduction of at least 75% in the subject's total IgG level compared to baseline by 7 days after initial administration. In some embodiments, the method results in a reduction of at least 85% in the subject's total IgG level compared to baseline by 7 days after initial administration.

[0022] In some embodiments, the autoimmune disease is a progressive autoimmune disease. In some embodiments, the autoimmune disease is CIDP. In some embodiments, the autoimmune disease is myasthenia gravis.

[0023] In another respect, this article provides a method for controlling the onset of autoimmune disease in a subject being treated with anti-FcRn therapy, the method comprising administering at least four doses of anti-FcRn antibody to the subject.

[0024] In some embodiments, the method includes administering anti-FcRn antibodies on days 1, 8, 15, and 22. In some embodiments, the method includes administering anti-FcRn antibodies on days 1, 4, 8, 15, and 22. In some embodiments, the anti-FcRn antibody is battolimab. In some embodiments, battolimab is administered subcutaneously. In some embodiments, the method includes administering 680 mg of battolimab. In some embodiments, the anti-FcRn antibody is IMVT-1402. In some embodiments, IMVT-1402 is administered subcutaneously. In some embodiments, the method includes administering 600 mg of IMVT-1402. In some embodiments, the autoimmune disease is a progressive autoimmune disease. In some embodiments, intravenous immunoglobulin (IVIg) has been administered to the subject. In some embodiments, IVIg is further administered to the subject. In some embodiments, the autoimmune disease is being treated with PLEX. In some embodiments, the autoimmune disease is CIDP. In some implementations, the autoimmune disease is myasthenia gravis.

[0025] In some aspects, this disclosure provides a method for treating a subject with Graves' disease (GD), the method comprising administering 550 to 700 mg of an anti-FcRn antibody to the subject once weekly. In some embodiments, this disclosure provides a method for treating a subject with Graves' disease (GD), the method comprising administering 200 to 300 mg of an anti-FcRn antibody (e.g., 300 mg IMVT-1402) to the subject once weekly. In some embodiments, this disclosure provides a method for treating a subject with Graves' disease (GD), the method comprising administering 550 to 700 mg of an anti-FcRn antibody to the subject once weekly for 20 to 60 weeks.

[0026] In some aspects, this disclosure provides a method for treating or preventing thyroid eye disease (TED) in a subject with Graves' disease (GD), the method comprising administering 550 to 700 mg of an anti-FcRn antibody (e.g., 600 mg IMVT-1402) to the subject once weekly.

[0027] In some aspects, this disclosure provides a method for treating or preventing thyroid eye disease (TED) in a subject with Graves' disease (GD), the method comprising administering 200 to 400 mg of an anti-FcRn antibody (e.g., 300 mg IMVT-1402) to the subject once weekly. In some aspects, this disclosure provides a method for treating or preventing thyroid eye disease (TED) in a subject with Graves' disease (GD), the method comprising administering 200 to 400 mg or 550 to 700 mg of an anti-FcRn antibody to the subject once weekly for 20 to 60 weeks or for 20 to 30 weeks. In some embodiments, the administration results in a reduction of the subject's TED symptoms relative to before the administration. In some embodiments, the application reduces the protrusion of the subject's eyes compared to before the application. In some embodiments, the application reduces the eyelid aperture of the subject compared to before the application. In some embodiments, the application reduces the thyroid volume of the subject compared to before the application.

[0028] In some aspects, this disclosure provides a method for inducing remission in a subject suffering from Graves' disease (GD), the method comprising administering 550 to 700 mg of an anti-FcRn antibody to the subject once weekly.

[0029] In some embodiments, the antibody is administered to the subject for a period of 20 to 60 weeks. In some embodiments, the antibody is administered to the subject for 52 weeks. In some embodiments, the antibody is administered to the subject for 26 weeks. In some embodiments, the antibody is administered to the subject at a reduced dose after 26 weeks. In some embodiments, a reduced dose of 300 mg of the antibody is administered to the subject once weekly. In some embodiments, a reduced dose of 300 mg of the antibody is administered to the subject once weekly for 26 weeks.

[0030] In some embodiments, the subject is administered 600 mg of anti-FcRn antibody once weekly for 20 to 60 weeks. In some embodiments, the subject is administered 600 mg of anti-FcRn antibody once weekly for 52 weeks. In some embodiments, the subject is administered 600 mg of anti-FcRn antibody once weekly for 26 weeks.

[0031] In some embodiments, the anti-FcRn antibody is IMVT-1402. In some embodiments, the antibody comprises: a heavy chain variable region (VH) containing a heavy chain complementarity-determining region (HCDR) 1 containing the amino acid sequence of SEQ ID NO: 7, an HCDR2 containing the amino acid sequence of SEQ ID NO: 8, and an HCDR3 containing the amino acid sequence of SEQ ID NO: 9; and a light chain variable region containing a light chain complementarity-determining region (LCDR) 1 containing the amino acid sequence of SEQ ID NO: 10, an LCDR2 containing the amino acid sequence of SEQ ID NO: 11, and an LCDR3 containing the amino acid sequence of SEQ ID NO: 12. In some embodiments, the antibody comprises: a VH containing the amino acid sequence of SEQ ID NO: 15 and a VL containing the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises: a heavy chain containing the amino acid sequence of SEQ ID NO: 19 and a light chain containing the amino acid sequence of SEQ ID NO: 20. In some embodiments, the antibody comprises: a heavy chain comprising the amino acid sequence of SEQ ID NO: 21 and a light chain comprising the amino acid sequence of SEQ ID NO: 22.

[0032] In some implementations, the subject had significant hyperthyroidism prior to administration. In some implementations, the subject's baseline triiodothyronine (T3) level was above the upper limit of normal (ULN). In some implementations, the subject's baseline free thyroxine (FT4) level was above the ULN. In some implementations, the subject's baseline TSH level did not exceed the lower limit of normal (LLN).

[0033] In some embodiments, the subject had subclinical hyperthyroidism prior to administration. In some embodiments, the subject's T3 level was within the clinically normal T3 range. In some embodiments, the subject's FT4 level was within the clinically normal FT4 range. In some embodiments, the subject's thyroid-stimulating hormone (TSH) level was below 0.1 mU / L.

[0034] In some embodiments, the subject is receiving an antithyroid drug (ATD) at the time of administration. In some embodiments, the subject has previously received an antithyroid drug (ATD) for at least 3 months prior to administration. In some embodiments, the ATD is methimazole, carbimazole, or propylthiouracil. In some embodiments, the subject is receiving an ATD dose of at least 20 mg / day of methimazole prior to administration. In some embodiments, the subject is receiving an ATD dose of at least 30 mg / day of carbimazole prior to administration. In some embodiments, the subject is receiving an ATD dose of at least 200 mg / day of propylthiouracil prior to administration.

[0035] In some embodiments, the subject has been continuously receiving an antithyroid drug (ATD) for four weeks prior to baseline assessment. In some embodiments, the subject has been receiving an antithyroid drug (ATD) for at least six months prior to baseline assessment. In some embodiments, the ATD is methimazole, carbimazole, or propylthiouracil. In some embodiments, the subject is receiving an ATD dose of at least 15 mg / day of methimazole prior to administration. In some embodiments, the subject is receiving an ATD dose of at least 20 mg / day of carbimazole prior to administration. In some embodiments, the subject is receiving an ATD dose of at least 150 mg / day of propylthiouracil prior to administration.

[0036] In some embodiments, the subject receives an ATD concurrently. In some embodiments, the subject receives an ATD at a dose of at least 10 mg / day of methimazole. In some embodiments, the subject receives an ATD at a dose of at least 15 mg / day of carbimazole. In some embodiments, the subject receives an ATD at a dose of at least 100 mg / day of propylthiouracil.

[0037] In some implementations, the subject does not have or has not previously had hyperthyroidism that is not caused by GD.

[0038] In some implementations, the subject does not have toxic adenoma or toxic multinodular goiter.

[0039] In some implementations, the subject does not have a history of thyroid storm within six months prior to administration of an anti-FcRn antibody (such as IMVT-1402 or batolizumab).

[0040] In some implementations, the subject does not suffer from active autoimmune disease.

[0041] In some implementations, the subject does not have TED. In some implementations, the subject does not have moderate to severe active TED requiring immediate surgical intervention, corrective surgery, irradiation, and / or medical treatment.

[0042] In some implementations, the subject does not have a history of non-compliance with ATD therapy.

[0043] In some implementations, the anti-FcRn antibody is administered subcutaneously.

[0044] In some implementations, administration at or before week 25 induces euthyroidism in the subject.

[0045] In some implementations, administration of an anti-FcRn antibody (such as IMVT-1402 or batolizumab) reduces the subject's T3 level to the normal range.

[0046] In some embodiments, administration of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) reduces the subject's FT4 level to within the normal range. In some embodiments, administration of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) increases the subject's TSH level to within the normal range. In some embodiments, the subject discontinues ATD at or before week 26 of administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab).

[0047] In some embodiments, administration induces normalization of thyroid function in the subject at or before week 52. In some embodiments, administration lowers the subject's T3 level to the normal range. In some embodiments, administration lowers the subject's FT4 level to the normal range. In some embodiments, administration raises the subject's TSH level to the normal range. In some embodiments, the subject discontinues ATD at or before week 52.

[0048] In some implementations, the application prevents or improves one or more of the following ocular symptoms in the subject: bulging eyes; gritty feeling in the eyes; eye pressure or pain; eyelid retraction; red or inflamed eyes; light sensitivity; blurred or diplopia, or vision loss.

[0049] In some implementations, administration induces remission in the subject (i.e., achieving normal thyroid function for at least 6 months or longer after discontinuation of anti-FcRn and / or ATD therapy).

[0050] In some aspects, this disclosure provides a method for treating a subject with rheumatoid arthritis (RA), the method comprising administering 550 to 700 mg of an anti-FcRn antibody to the subject once weekly.

[0051] In some embodiments, a subject with RA is given 600 mg of anti-FcRn antibody once weekly. In some embodiments, the subject is given 300 mg of anti-FcRn antibody once weekly. In some embodiments, a subject with RA is given 600 mg of anti-FcRn antibody once weekly for at least 16 weeks, followed by (i) a weekly dose of 600 mg of anti-FcRn antibody; or (ii) a weekly dose of 300 mg of anti-FcRn antibody.

[0052] In some implementations, anti-FcRn antibodies are administered subcutaneously to subjects with RA.

[0053] In some implementations, the subject suffers from active RA.

[0054] In some embodiments, the subject has refractory RA. In some embodiments, the subject has moderate disease activity. In some embodiments, the subject's DAS28-ESR score is greater than 3.2. In some embodiments, the subject's CDAI score is greater than 10. In some embodiments, the subject has one or more symptoms suggestive of active RA. In some embodiments, the subject is unable to gradually reduce glucocorticoid therapy to less than 7.5 mg / day. In some embodiments, the subject shows rapid radiographic progression of RA, indicated by a change of ≥5 points in the van der Heijde-modified Sharp score over 1 year.

[0055] In some embodiments, subjects with RA are positive for rheumatoid factor (RF). In some embodiments, the synovial fluid of subjects with RA is positive for IgG or IgA RF. In some embodiments, the RF level of subjects with RA is higher than 25 U / ml. In some embodiments, the RF level of subjects with RA is higher than 100 U / ml.

[0056] In some implementations, subjects with RA test positive for anti-citrullinated protein autoantibodies (ACPA).

[0057] In some embodiments, subjects with RA have at least 6 / 68 tender and / or painful joints (TJCs) at baseline. In some embodiments, subjects with RA have at least 6 / 66 swollen joints (SJCs) at baseline.

[0058] In some implementations, the baseline circulating C-reactive protein (CRP) level of subjects with RA is at least 1.5 × ULN.

[0059] In some implementations, subjects with RA have a baseline disease activity score 28 (DAS28-CRP) greater than 4.1 as determined by C-reactive protein.

[0060] In some implementations, subjects with RA do not respond to two or three classes of biological (b) or targeted synthetic (ts) disease-modified antirheumatic drugs (b / tsDMARDs).

[0061] In some implementations, subjects with RA have been treated with biological TNF-α inhibitors (e.g., infliximab, certolizumab, golimumab, etanercept, adalimumab).

[0062] In some implementations, the subjects with RA have been treated with JAK inhibitors.

[0063] In some implementations, subjects with RA have been treated with bDMARDs other than TNF-α inhibitors.

[0064] In some implementations, subjects with RA respond to rituximab.

[0065] In some implementations, subjects with RA do not receive glucocorticoids at doses >10 mg / day.

[0066] In some implementations, subjects with RA did not receive three or more joint injections within six weeks prior to baseline assessment.

[0067] In some implementations, subjects with RA did not receive systemic glucocorticoids administered via intramuscular or intravenous (IV) injection within six weeks prior to baseline assessment.

[0068] In some implementations, the RF level of the object is reduced.

[0069] In some implementations, an ACAP that reduces the object is applied.

[0070] In some implementations, subjects with RA achieved an ACR20 response at week 14, week 16, or week 32 after administration of the anti-FcRn antibody.

[0071] In some implementations, subjects with RA showed at least a 20% improvement in TJC68 relative to baseline. In some implementations, subjects with RA showed at least a 20% improvement in SJC66 relative to baseline.

[0072] In some implementations, subjects with RA show at least a 20% improvement relative to baseline in at least three of the following parameters: (i) Physician Overall Disease Activity Assessment (PhGA); (ii) Patient Overall Disease Activity Assessment (PtGA); (iii) Patient Pain Assessment (100 mm VAS); (iv) Health Assessment Questionnaire-Disability Index (HAQ-DI); and (v) High Sensitivity C-Reactive Protein (hsCRP).

[0073] In some implementations, subjects with RA achieved an ACR20 response at week 14 or 16 of administration of the anti-FcRn antibody and showed changes in CDAI scores from week 16 to week 32 of administration.

[0074] In some implementations, subjects with RA achieved an ACR20 response at week 14 or week 16 of administration of the anti-FcRn antibody and exhibited changes in SDAI scores from week 16 to week 32 of administration.

[0075] In some embodiments, the anti-FcRn antibody is IMVT-1402. In some embodiments, the anti-FcRn antibody comprises: a heavy chain variable region (VH) containing a heavy chain complementarity-determining region (HCDR) 1 containing the amino acid sequence of SEQ ID NO: 7, an HCDR2 containing the amino acid sequence of SEQ ID NO: 8, and an HCDR3 containing the amino acid sequence of SEQ ID NO: 9; and a light chain variable region containing a light chain complementarity-determining region (LCDR) 1 containing the amino acid sequence of SEQ ID NO: 10, an LCDR2 containing the amino acid sequence of SEQ ID NO: 11, and an LCDR3 containing the amino acid sequence of SEQ ID NO: 12. In some embodiments, the antibody comprises: a VH containing the amino acid sequence of SEQ ID NO: 15 and a VL containing the amino acid sequence of SEQ ID NO: 16. In some embodiments, the antibody comprises: a heavy chain containing the amino acid sequence of SEQ ID NO: 19 and a light chain containing the amino acid sequence of SEQ ID NO: 20.

[0076] In some embodiments, the anti-FcRn antibody comprises: a heavy chain comprising the amino acid sequence of SEQ ID NO: 21 and a light chain comprising the amino acid sequence of SEQ ID NO: 22.

[0077] In some aspects, this disclosure provides a method for treating Graves' disease (GD) in a subject receiving an antithyroid drug (ATD) at a dose, the method comprising: (i) administering an anti-FcRn antibody to the subject at a dose in the range of 580 to 700 mg; (ii) measuring the subject's T3 and T4 levels; (iii) if the T3 and / or T4 levels are below the ULN, reducing the dose of the ATD or discontinuing the ATD; (iii) reducing the dose of the anti-FcRn antibody to a dose in the range of 280 to 400 mg / dose; and (iv) increasing the dose of the ATD or restarting the subject's ATD to maintain T3 and T4 levels below the ULN.

[0078] In some aspects, this disclosure provides a method for treating Graves' disease (GD) in a subject receiving an antithyroid drug (ATD) at a dose, the method comprising: (i) administering an anti-FcRn antibody to the subject; (ii) measuring the subject's T3 and T4 levels; (iii) if the T3 and / or T4 levels are below the ULN, reducing the dose of the ATD or discontinuing the ATD; (iii) reducing the dose of the anti-FcRn antibody to a dose in the range of 280 to 400 mg / dose; and (iv) increasing the dose of the ATD or restarting the subject's ATD to maintain T3 and T4 levels below the ULN.

[0079] In some aspects, this disclosure provides a method for treating Graves' disease (GD) in a subject receiving an antithyroid drug (ATD) at a dose, the method comprising: (i) administering an anti-FcRn antibody to the subject at a dose in the range of 580 to 700 mg; (ii) measuring the subject's T3 and T4 levels; (iii) if the T3 and / or T4 levels are below the ULN, reducing the dose of the ATD or discontinuing the ATD; and (iii) maintaining the dose of the anti-FcRn antibody while administering a low dose of the ATD or not administering the ATD to the subject to maintain the T3 and T4 levels below the ULN.

[0080] In some aspects, this disclosure provides a method for treating Graves' disease (GD) in a subject receiving an antithyroid drug (ATD) at a dose, the method comprising: (i) administering an anti-FcRn antibody to the subject; (ii) measuring the subject's T3 and T4 levels; (iii) if the T3 and / or T4 levels are below the ULN, reducing the dose of the ATD or discontinuing the ATD; and (iii) maintaining the dose of the anti-FcRn antibody while administering a low dose of the ATD or not administering the ATD to the subject to maintain the T3 and T4 levels below the ULN.

[0081] In some aspects, this disclosure provides a method for treating a subject with myasthenia gravis (MG) comprising administering 550 to 700 mg of an anti-FcRn antibody (e.g., IMVT-1402 or bartolimab) to the subject once weekly.

[0082] In some aspects, this disclosure provides a method for inducing remission in a subject suffering from myasthenia gravis (MG), the method comprising administering 550 to 700 mg of an anti-FcRn antibody to the subject once a week.

[0083] In some implementations, 600 mg of anti-FcRn antibody is administered to subjects with MG once a week.

[0084] In some embodiments, antibodies are administered to subjects with MG for a period of 20 to 60 weeks. In some embodiments, antibodies are administered to subjects with MG for 52 weeks. In some embodiments, antibodies are administered to subjects with MG for 26 weeks.

[0085] In some embodiments, the antibody is administered to subjects with MG at a reduced dose after 26 weeks. In some embodiments, a reduced dose of 300 mg of the antibody is administered to subjects with MG once weekly. In some embodiments, a reduced dose of 300 mg of the antibody is administered to subjects with MG once weekly for 26 weeks. In some embodiments, a reduced dose of 300 mg of the antibody is administered to subjects with MG once weekly indefinitely.

[0086] In some embodiments, subjects with myocardial infarction (MG) are positive for anti-acetylcholine receptor (AChR) autoantibodies (anti-AChR+). In some embodiments, subjects with MG are positive for anti-muscle-specific kinase (MuSK) autoantibodies (anti-MuSK+). In some embodiments, subjects with MG are positive for anti-lipoprotein receptor-associated protein 4 (LRP4) autoantibodies (anti-LRP4+).

[0087] In some implementations, administration of an anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) reduces the level of anti-AChR autoantibodies in the subject's serum relative to the level of anti-AChR autoantibodies in the serum prior to administration.

[0088] In some implementations, administration of anti-FcRn antibodies (such as IMVT-1402 or batolizumab) reduces the level of anti-MuSK autoantibodies in the serum of subjects with MG compared to the level of anti-MuSK autoantibodies in the serum before administration.

[0089] In some embodiments, administration of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) reduces the level of anti-LRP4 autoantibodies in the serum of a subject with MG relative to the level of anti-LRP4 autoantibodies in the serum prior to administration. In some embodiments, administration of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) prevents or improves one or more of the following symptoms in a subject with MG: weakness of some or all muscles of the body, dilated vision, slurred speech, weakness of the arms, falls, unsteady gait, dysphagia, chronic fatigue, and / or dyspnea.

[0090] In some aspects, this disclosure provides a method for treating a subject with chronic inflammatory demyelinating polyneuropathy (CIDP), the method comprising administering 200 to 400 mg of an anti-FcRn antibody (e.g., IMVT-1402 or bartolimab) to the subject once weekly.

[0091] In some aspects, this disclosure provides a method for treating a subject with chronic inflammatory demyelinating polyneuropathy (CIDP), the method comprising administering 550 to 700 mg of an anti-FcRn antibody (e.g., IMVT-1402 or bartolimab) to the subject once weekly.

[0092] In some embodiments, anti-FcRn antibodies are administered to subjects with CIDP for 20 to 60 weeks. In some embodiments, anti-FcRn antibodies are administered to subjects with CIDP for 24 weeks.

[0093] In some embodiments, the method further includes administering a loading dose of anti-FcRn antibody to subjects with CIDP on days 3 through 5 of the first week of administration.

[0094] In some embodiments, the loading dose of anti-FcRn antibody is administered to subjects with CIDP on day 4 of the first week of administration. In some embodiments, the loading dose of anti-FcRn antibody is the same as the weekly dose of anti-FcRn antibody. In some embodiments, the loading dose of anti-FcRn antibody is 600 mg.

[0095] In some embodiments, the anti-FcRn antibody is administered to subjects with CIDP for an additional 52 weeks. In some embodiments, 600 mg of anti-FcRn antibody is administered to subjects with CIDP once weekly. In some embodiments, 300 mg of anti-FcRn antibody is administered to subjects with CIDP once weekly.

[0096] In some embodiments, the method further includes administering a loading dose of anti-FcRn antibody to the subject with CIDP on days 3 through 5 of the first week of an additional 52 weeks. In some embodiments, the loading dose of anti-FcRn antibody is administered to the subject on day 4 of the first week of the additional 52 weeks. In some embodiments, the loading dose of anti-FcRn antibody is the same as the weekly dose of anti-FcRn antibody. In some embodiments, the loading dose of anti-FcRn antibody is 600 mg.

[0097] In some implementations, the subject has typical CIDP. In some implementations, the subject has a CIDP variant. In some implementations, the CIDP variant is multifocal CIDP. In some implementations, the CIDP variant is motor CIDP. In some implementations, the subject does not have sensory CIDP. In some implementations, the subject does not have remote CIDP.

[0098] In some embodiments, the subject with CIDP is receiving or has received first-line therapy for CIDP. In some embodiments, the first-line therapy for CIDP is corticosteroids. In some embodiments, the subject with CIDP is receiving oral corticosteroids daily or every other day. In some embodiments, the subject with CIDP is receiving corticosteroids via a pulsed regimen. In some embodiments, the subject with CIDP gradually reduces corticosteroids while receiving anti-FcRn antibodies. In some embodiments, the subject with CIDP discontinues corticosteroids before receiving anti-FcRn antibodies.

[0099] In some embodiments, the first-line treatment for CIDP is immunoglobulin (Ig) therapy. In some embodiments, Ig therapy is intravenous Ig infusion (IVIg). In some embodiments, Ig therapy is sucrose infusion (SCIg). In some embodiments, subjects with CIDP discontinue Ig therapy before receiving anti-FcRn antibodies.

[0100] In some implementations, the first-line treatment for CIDP is plasma exchange (PLEX).

[0101] In some embodiments, subjects with CIDP, as measured by the Adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT) score, experienced a relapse during a 24-week period of anti-FcRn antibody (e.g., IMVT-1402 or battolimab). In some embodiments, subjects with CIDP, as measured by the aINCAT score, did not experience a relapse during a 24-week period of anti-FcRn antibody (e.g., IMVT-1402 or battolimab).

[0102] In some implementations, the application of anti-FcRn antibodies (such as IMVT-1402 or battolimab) increases the average grip strength relative to before the application.

[0103] In some implementations, administration of anti-FcRn antibodies (such as IMVT-1402 or batolizumab) resulted in an improvement in the Inflammatory Rasch-built Overall Disability Scale (I-RODS) score compared to before administration.

[0104] In some implementations, administration of anti-FcRn antibodies (such as IMVT-1402 or batolizumab) resulted in an improvement in the MCR-SS score relative to the initial score.

[0105] In some implementations, administration of anti-FcRn antibodies (such as IMVT-1402 or battolimab) resulted in a decrease in the timed stand-up walk (TUG) test score relative to before administration.

[0106] In some implementations, administration of anti-FcRn antibodies (such as IMVT-1402 or batolizumab) reduces total IgG relative to the level before administration.

[0107] In some implementations, the administration of anti-FcRn antibodies (such as IMVT-1402 or batolizumab) reduces the IgG subclass relative to the level before administration.

[0108] In some implementations, the administration of anti-FcRn antibodies (such as IMVT-1402 or battolimab) reduces the number of autoantibodies targeting myelin compared to before administration.

[0109] In some implementations, the administration of an anti-FcRn antibody (such as IMVT-1402 or bartolimab) reduces the amount of immune complexes (IC) relative to before administration.

[0110] In some implementations, administration of an anti-FcRn antibody (such as IMVT-1402 or battolimab) reduces the number of neurocilia light chains (NfL) relative to before administration. Attached Figure Description

[0111] Figure 1 This shows a representative clinical study protocol for healthy subjects. IV = intravenous; MAD = multiple escalation doses; PK = pharmacokinetics; QW = once a week; SAD = single escalation dose; SC = subcutaneous.

[0112] Figure 2 Showing the relationship between mean (SD) albumin concentration (SAD) and nominal time (linear scale) (safety analysis set). SAD = single escalation dose; SC = subcutaneous; SD = standard deviation. Note: Baseline is defined as the last non-missing value before the first treatment. Results including "<" or ">" are estimated as numerical portions.

[0113] Figure 3 The mean (SD) albumin concentration (MAD) is shown as a linear scale over nominal time (safety analysis set). MAD = multiple dose escalations; QW = once a week; SC = subcutaneous; SD = standard deviation. Note: Baseline is defined as the last non-missing value before the first treatment. Results including "<" or ">" are estimated as numerical portions.

[0114] Figure 4 This shows the relationship between mean (SD) albumin concentration of alternative dosing regimens and nominal time (linear scale) (safety analysis set). SC = subcutaneous; SD = standard deviation.

[0115] Figure 5 Showing the relationship between mean (SD) total cholesterol concentration (SAD) and nominal time (linear scale) (safety analysis set). IV = intravenous; N = number of participants; SAD = single escalation dose; SC = subcutaneous; SD = standard deviation. Note: Baseline is defined as the last non-missing value before the first treatment. Results including "<" or ">" are estimated as numerical portions.

[0116] Figure 6 Showing the relationship between mean (SD) LDL cholesterol concentration and nominal time (linear scale) for SAD (safety analysis set). IV = intravenous; LDL = low-density lipoprotein; N = number of participants; SAD = single escalation dose; SC = subcutaneous; SD = standard deviation. Note: Baseline is defined as the last non-missing value before the first treatment. Results including "<" or ">" are estimated as numerical portions.

[0117] Figure 7The relationship between mean (SD) total cholesterol concentration (MAD) and nominal time (linear scale) is shown (safety analysis set). MAD = multiple dose escalations; N = number of participants; SC = subcutaneous; SD = standard deviation; QW = once a week. Note: Baseline is defined as the last non-missing value before the first treatment. Results including "<" or ">" are estimated as numerical portions.

[0118] Figure 8 The relationship between mean (SD) LDL cholesterol concentration and nominal time (linear scale) is shown for the safety analysis set. LDL = low-density lipoprotein; MAD = multiple escalation doses; N = number of participants; QW = once a week; SC = subcutaneous; SD = standard deviation. Note: Baseline is defined as the last non-missing value before the first treatment. Results including "<" or ">" are estimated as numerical portions.

[0119] Figure 9 This shows the relationship between mean (SD) total cholesterol concentration of the alternative dose regimen and nominal time (linear scale) (safety analysis set). N = number of participants; SC = subcutaneous; SD = standard deviation; QW = once per week. Note: Baseline is defined as the last non-missing value before the first treatment. Results including "<" or ">" are estimated as numerical portions.

[0120] Figure 10 Showing the relationship between mean (SD) LDL cholesterol concentration and nominal time (linear scale) of alternative dosing regimens (safety analysis set). LDL = low-density lipoprotein; MAD = multiple escalation doses; N = number of participants; QW = once a week; SC = subcutaneous; SD = standard deviation. Note: Baseline is defined as the last non-missing value before the first treatment. Results including "<" or ">" are estimated as numerical portions.

[0121] Figure 11 This chart shows the mean (SD) serum concentration of IMVT-1402 in healthy participants after SAD IV administration over time (semi-logarithmic scale) (pharmacokinetic analysis set). BLQ = below the limit of quantitation; IV = intravenous; LLOQ = lower limit of quantitation; N = number of participants in the cohort; SAD = single escalation dose; SD = standard deviation. The LLOQ value for IMVT-1402 is 0.01 mg / L (dashed line). Note: All BLQ values ​​are presented as half of the LLOQ. Bars with negative mean ± SD values ​​are not presented at time points where the SD value is greater than the mean.

[0122] Figure 12This chart shows the mean (SD) concentration of serum IMVT-1402 in healthy participants after administration of SAD and SC, versus time (semi-logarithmic scale) (pharmacokinetic analysis set). BLQ = below the limit of quantitation; LLOQ = lower limit of quantitation; single escalation dose = SAD; SC = subcutaneous. Note: The LLOQ value for IMVT-1402 is 0.01 mg / L (dashed line). All BLQ values ​​are presented as half of the LLOQ. No negative mean ± SD bars are shown at time points where the SD value is greater than the mean.

[0123] Figure 13 This chart shows the mean (SD) concentration of serum IMVT-1402 as a function of time (semi-logarithmic scale) after MAD SC administration on days 1 and 22 in healthy participants (pharmacokinetic analysis set). BLQ = below the limit of quantitation; LLOQ = lower limit of quantitation; MAD = multiple escalation doses; SC = subcutaneous; SD = standard deviation. The LLOQ value for IMVT-1402 is 0.01 mg / L (dashed line). All BLQ values ​​are presented as half of the LLOQ. No negative mean ± SD bars are shown at time points where the SD value is greater than the mean. Note: In the 300 mg MAD cohort, one participant prematurely terminated the cohort after a visit on day 15.

[0124] Figure 14 This chart shows the mean (SD) concentration of serum IMVT-1402 as a function of time (semi-logarithmic scale) after SC administration in healthy participants with alternative dosing regimens (pharmacokinetic analysis set). BLQ = below the limit of quantitation; LLOQ = lower limit of quantitation; SC = subcutaneous; SD = standard deviation. The LLOQ value for IMVT-1402 is 0.01 mg / L (dashed line). All BLQ values ​​are presented as half of the LLOQ. No negative mean ± SD bars are shown at time points where the SD value is greater than the mean.

[0125] Figure 15 This shows the relationship between the mean (SD) percentage change in total immunoglobulin G (IgG) subclass concentrations relative to baseline and nominal time (linear scale) in the SAD IV cohort (pharmacodynamic analysis set). Abbreviations: IgG = Immunoglobulin G; IV = Intravenous; N = Number of participants; SAD = Single escalation dose; SD = Standard deviation. Note: Baseline is defined as the last non-missing value prior to the first dose of the study treatment.

[0126] Figure 16This shows the relationship between the mean (SD) percentage change in total immunoglobulin G (IgG) subclass concentrations relative to baseline and nominal time (linear scale) in the SAD SC cohort (pharmacodynamic analysis set). Abbreviations: IgG = Immunoglobulin G; IV = Intravenous; N = Number of participants; SAD = Single escalation dose; SC = Subcutaneous; SD = Standard deviation. Note: Baseline is defined as the last non-missing value prior to the first dose of the study treatment.

[0127] Figure 17 This pharmacodynamic analysis set shows the percentage change in total immunoglobulin G (IgG) concentration relative to baseline over nominal time (linear scale) in the MAD cohort. IgG = Immunoglobulin G; MAD = Multiple escalation doses; SC = Subcutaneous; SD = Standard deviation. Note: Baseline is defined as the last non-missing value prior to the first dose of the study treatment.

[0128] Figure 18 This shows the relationship (linear scale) between the mean (SD) percentage change in total immunoglobulin G (IgG) and IgG subclass concentrations relative to baseline and nominal time for alternative dosing regimens (pharmacodynamic analysis set). IgG = Immunoglobulin G; SC = Subcutaneous; SD = Standard deviation; Note: Baseline is the last non-missing value before the first treatment.

[0129] Figure 19 This shows the percentage change in total immunoglobulin G (IgG) concentration in SAD relative to baseline over actual time, based on ADA status (pharmacodynamic analysis set). ADA = anti-drug antibody; IgG = immunoglobulin G; IV = intravenous; N = number of participants; SAD = single escalation dose; SC = subcutaneous. Note: Baseline is defined as the last non-missing value before the first treatment. Results including "<" or ">" are estimated as numerical portions.

[0130] Figure 20 This shows the percentage change in total immunoglobulin G (IgG) concentration in MAD according to ADA status relative to baseline over actual time (pharmacodynamic analysis set). ADA = anti-drug antibody; IgG = immunoglobulin G; MAD = multiple escalation doses; N = number of participants; QW = once a week; SC = subcutaneous. Note: Baseline is defined as the last non-missing value before the first treatment. Results including "<" or ">" are estimated as numerical portions.

[0131] Figure 21This shows the percentage change in total immunoglobulin G (IgG) concentration relative to baseline by ADA status over actual time (linear scale) (pharmacodynamic analysis set). ADA = anti-drug antibody; IgG = immunoglobulin G; MAD = multiple escalation doses; N = number of participants; SC = subcutaneous. Note: Baseline is defined as the last non-missing value before the first treatment. Results including "<" or ">" are estimated as numerical portions.

[0132] Figure 22 This shows the relationship between the mean (SD) percentage change in circulating immune complex concentration (MAD) relative to baseline and nominal time (linear scale) (safety analysis set). MAD = multiple dose escalations; pchg = percentage change; SC = subcutaneous; SD = standard deviation; QW = once weekly. Note: Baseline is defined as the last non-missing value before the first treatment. Results including "<" or ">" are estimated as numerical portions. pchg calculations are based on estimates.

[0133] Figure 23 This shows the relationship between the mean (SD) percentage change in circulating immune complex concentration relative to baseline and nominal time for alternative dosing regimens (linear scale) (safety analysis set). pchg = percentage change; SC = subcutaneous; SD = standard deviation. Note: Baseline is defined as the last non-missing value before the first treatment. Results including "<" or ">" are estimated as numerical portions. pchg calculations are based on estimates.

[0134] Figure 24 A plot showing the effects of rheumatoid arthritis (RA): the interactions between cells, cytokines, and therapies used in the RA quantitative systems pharmacology (QSP) model and their impact on inflammation.

[0135] Figure 25 This chart shows a representative clinical study of Graves' disease. ATD = antithyroid drug; D = day; EOS = study end; ET = early termination; EuThy = euthyroid; N = no; QW = once a week; R = randomization; SC = subcutaneous; SFU = safety follow-up; TRAb = TSHR antibody; W = week; Y = yes. *Confirmed by two consecutive assessments.

[0136] Figure 26 This chart shows representative clinical studies. *ACR20 criteria were met at weeks 14 and 16. NR = ACR20 criteria were not met at weeks 14 and 16.

[0137] Figure 27This study shows the relationship between ATD dose change and nominal time after weekly SC doses of battolimumab in a safety analysis set of 21 participants with Graves' disease who either interrupted treatment early or reached week 12. ATD = antithyroid drug; Q1 = first quartile; Q3 = third quartile; SC = subcutaneous. Note: Participants with hyperthyroidism received battolimumab 680 mg SC QW for 12 weeks.

[0138] Figure 28 This study shows the relationship between ATD dose change and nominal time after weekly SC doses of battolimumab in a safety analysis set of subjects with Graves' disease (N=14) who interrupted treatment early or reached week 24. ATD = antithyroid drug; Q1 = first quartile; Q3 = third quartile; SC = subcutaneous. Note: Participants with hyperthyroidism received battolimumab 680 mg SC QW for 12 weeks, followed by battolimumab 340 mg SC QW for another 12 weeks starting on day 85.

[0139] Figure 29 A schematic overview of the design for a phase 2 Graves' disease trial of battolimab.

[0140] Figure 30 This shows the percentage change in total IgG relative to baseline at weeks 6, 12, or 24 in Graves' disease patients receiving batolizumab treatment.

[0141] Figure 31 This shows the free serum T3 levels over time in Graves' disease patients treated with batolizumab.

[0142] Figure 32 This shows the free serum T4 levels over time in Graves' disease patients treated with batolizumab.

[0143] Figure 33 The free serum T3 / free serum T4 levels (top) and TRAb / TSH levels (bottom) over time are shown in subjects with Graves' disease who received batolizumab treatment while reducing the CMZ dose to discontinue CMS treatment.

[0144] Figure 34 The figure below shows the level of bulging eye / eyelid opening and thyroid volume over time while receiving batotimab treatment and reducing the CMZ dose to stop CMS treatment (see figure below).

[0145] Figure 35 This shows the proportion of Graves' disease patients whose FT3 and FT4 were equal to or lower than ULN when receiving batolizumab treatment.

[0146] Figure 36This shows the proportion of Graves' disease patients who received batolimumab treatment concurrently with a reduced ATD dose and whose FT3 and FT4 were equal to or lower than ULN when ATD was discontinued.

[0147] Figure 37 This shows the proportion of Graves' disease patients whose FT3 and FT4 were equal to or lower than ULN when receiving battolimumab treatment while receiving a reduced dose of ATD or discontinuing ATD.

[0148] Figure 38 High-dose batolizumab showed that it drove rapid normalization of T3 and T4 and a gradual decrease in ATD in patients with Graves' disease.

[0149] Figure 39 The study showed that a significant reduction in IgG at 24 weeks was associated with a significantly higher rate of non-ATD responders.

[0150] Figure 40 This is a schematic diagram of an exemplary study related to myasthenia gravis (MG).

[0151] Figure 41 This is an illustrative diagram of an exemplary study associated with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Detailed Implementation

[0152] This document provides methods for improving anti-FcRn therapy and for treating autoimmune diseases (such as Graves' disease (GD), thyroid eye disease (TED), rheumatoid arthritis (RA), myasthenia gravis (MG), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), etc.) and for treating acute exacerbations of autoimmune diseases. In some embodiments, this disclosure provides treatment regimens for various autoimmune diseases (such as GD, RA, MG, CIDP, etc.) that impart therapeutic effects such as reduction of autoantibodies, improvement / prevention of thyroid eye disease (TED) symptoms, and restoration to normal thyroid function. In some embodiments, such methods include administering one or more doses (e.g., loading doses) of an anti-FcRn antibody (e.g., batopilimab or IMVT-1402).

[0153] Anti-FcRn antibody

[0154] In various embodiments of the treatment methods disclosed herein, anti-FcRn antibodies or antigen-binding fragments can non-competitively inhibit the binding of at least one autoantibody and / or pathogenic antibody (e.g., at least one IgG) to FcRn at physiological pH (i.e., pH 7.0 to 7.4). It is not intended to be theoretically correct, but it is believed that FcRn binds to its ligand (i.e., IgG) and does not substantially exhibit affinity for IgG at physiological pH rather than acidic pH. Therefore, in various embodiments, at physiological pH, anti-FcRn antibodies or antigen-binding fragments can act as non-competitive inhibitors of IgG binding to FcRn, and the binding of anti-FcRn antibodies or antigen-binding fragments to FcRn is unaffected by the presence of IgG. Therefore, in various embodiments, anti-FcRn antibodies or antigen-binding fragments that bind specifically to FcRn in a non-pH-dependent manner and non-competitively with IgG have the advantage over conventional competitive inhibitors (i.e., antibodies that competitively bind to FcRn with IgG) because they can provide therapeutic or preventive effects through FcRn-mediated IgG signaling even at very low concentrations.

[0155] Furthermore, in various embodiments, during the intracellular migration process in the FcRn-bound state, anti-FcRn antibodies or antigen-binding fragments can maintain their binding to FcRn with a higher affinity than IgG in the blood. Therefore, in various embodiments, anti-FcRn antibodies or antigen-binding fragments can inhibit the binding of IgG to FcRn even in endosomes with an acidic pH environment where IgG can bind to FcRn, thereby promoting IgG clearance.

[0156] In some embodiments, the anti-FcRn antibody or antigen-binding fragment is bartolimab (also referred to herein as HL161BKN and RVT-1401). RVT-1401 / bartolimab is also described, for example, in International Patent Application Publication WO2015 / 167293 (where it is referred to as HL161BKN), which is incorporated herein by reference in its entirety.

[0157] In some embodiments, the anti-FcRn antibody or its antigen-binding fragment is IMVT-1402. IMVT-1402 is also described in International Patent Application No. PCT / US2023 / 067539 (which is also referred to as HL161ANS), which is incorporated herein by reference in its entirety.

[0158] The CDR sequences of batolizumab and IMVT-1402 are shown in Table 1.

[0159] Table 1: CDR sequences of the heavy and light chain variable regions of selected human FcRn antibodies

[0160]

[0161] In some embodiments, the antibody or antigen-binding fragment comprises: three heavy chain CDR amino acid sequences of SEQ ID No: 1 (HCDR1), SEQ ID No: 2 (HCDR2), and SEQ ID No: 3 (HCDR3); and three light chain CDR amino acid sequences of SEQ ID No: 4 (LCDR1), SEQ ID No: 5 (LCDR2), and SEQ ID No: 6 (LCDR3). In some embodiments, the antibody or antigen-binding fragment comprises: three heavy chain CDR amino acid sequences of SEQ ID No: 7 (HCDR1), SEQ ID No: 8 (HCDR2), and SEQ ID No: 9 (HCDR3); and three light chain CDR amino acid sequences of SEQ ID No: 10 (LCDR1), SEQ ID No: 11 (LCDR2), and SEQ ID No: 12 (LCDR3).

[0162] Exemplary heavy and light chain variable regions of anti-FcRn antibodies are shown in Table 2.

[0163] Table 2: Amino acid sequences of the heavy and light chain variable regions of the selected human FcRn antibodies

[0164]

[0165] In some embodiments, the antibody or antigen-binding fragment comprises: a heavy chain variable region comprising an amino acid sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence shown in SEQ ID No: 13; and a light chain variable region comprising an amino acid sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence shown in SEQ ID No: 14. In some embodiments, the antibody or antigen-binding fragment comprises: heavy chain amino acids comprising an amino acid sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence shown in SEQ ID No: 15; and light chain amino acids comprising an amino acid sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence shown in SEQ ID No: 16.

[0166] In some embodiments, the antibody or antigen-binding fragment comprises the heavy chain variable region amino acid sequence of SEQ ID No: 13 and the light chain variable region amino acid sequence of SEQ ID No: 14. In some embodiments, the antibody or antigen-binding fragment comprises the heavy chain amino acid sequence of SEQ ID No: 15 and the light chain amino acid sequence of SEQ ID No: 16.

[0167] Exemplary heavy and light chains of anti-FcRn antibodies are shown in Table 3.

[0168] Table 3: Amino acid sequences of the full-length heavy and light chains of the selected human FcRn antibodies.

[0169]

[0170]

[0171] In some embodiments, the antibody or antigen-binding fragment comprises: a heavy chain comprising an amino acid sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence shown in SEQ ID No: 17, 19, or 21; and a light chain comprising an amino acid sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence shown in SEQ ID No: 18, 20, or 22. In some embodiments, the antibody or antigen-binding fragment comprises: a heavy chain comprising the sequence shown in SEQ ID No: 17, 19, or 21; and a light chain comprising the sequence shown in SEQ ID No: 18, 20, or 22.

[0172] "Affinity" refers to the strength of the interaction between an antibody and an antigen at a single antigenic site. Within each antigenic site, the variable region of the antibody "arm" interacts with the antigen at multiple sites through weak non-covalent forces. Generally speaking, the stronger the interaction, the higher the affinity.

[0173] As used herein, the terms "specificity," "specifically binds," and "binds specifically" refer to the binding reaction between an antibody or its antigen-binding fragment (e.g., an anti-FcRn antibody or its antigen-binding fragment) and a target antigen (e.g., FcRn) in a heterogeneous population of proteins and other biological agents. The binding specificity of an antibody can be tested by comparing binding to an appropriate antigen with binding to a substitute antigen or a mixture of antigens under a given set of conditions. An antibody is considered specific if it binds to an appropriate antigen with an affinity at least 2, 5, or 10 times (or higher) greater than that of the substitute antigen or a mixture of antigens.

[0174] "Specific antibody" or "target-specific antibody" is an antibody that binds only to a target antigen (e.g., FcRn) but does not bind to (or exhibits minimal binding to) other antigens. In some embodiments, the K-cell structure of the antibody that specifically binds to the target antigen (e.g., FcRn) or its antigen-binding fragment is... D Less than 1×10 at pH 6.0 or pH 7.4 -6 M, below 1×10-7 M, below 1×10 -8 M, below 1×10 -9 M, below 1×10 -10 M, below 1×10 -11 M, below 1×10 -12 M or less than 1×10 -13 M. In some implementations, K D At pH 6.0 or pH 7.4, it is approximately 0.01 nM to approximately 2 nM. In some embodiments, K D At pH 7.4, it is approximately 300 pM or less to approximately 2 nM or less. In some embodiments, K D At pH 6.0, it is approximately 2 nM or lower up to 900 pM or lower.

[0175] As used in this article, the term "K" D "" refers to the equilibrium dissociation constant of antibody-antigen binding, which is determined by k d With k a The ratio (i.e., k) d / k a It is obtained and is generally expressed as molar concentration (M). The term "k" is used to describe the concentration of molar concentration. assoc "or "k a "" refers to the association rate of a specific antibody-antigen interaction, while the term "k" refers to the rate of association of a specific antibody-antigen interaction. dis "or "k d "k" refers to the dissociation rate of a specific antibody-antigen interaction. d and / or k a Measurements can be performed at 25°C or 37°C. Kc of antibody and antigen-binding fragments. D The value can be determined using methods recognized in the art (see, for example, Pollard, Mol. Biol. Cell 21(23):4061-7, 2010). In some embodiments, K D Measurements are taken via direct binding and / or competitive binding analyses (e.g., surface plasmon resonance and / or competitive ELISA). In some implementations, K... D Measured via surface plasmon resonance (e.g., human FcRn immobilized surface plasmon resonance). In some embodiments, the Kc of the anti-FcRn antibody or antigen-binding fragment disclosed herein is measured. D Measurements were performed using human FcRn-immobilized surface plasmon resonance.

[0176] In some embodiments of the treatments, uses, and compositions disclosed herein, the K-band of anti-FcRn antibodies or antigen-binding fragments is determined, for example, by surface plasmon resonance. DThe dissociation constant is approximately 0.01 nM to 2 nM at pH 6.0 or pH 7.4. In some embodiments, the Kc of the anti-FcRn antibody or antigen-binding fragment is determined, for example, by surface plasmon resonance. D At pH 7.4, it is approximately 300 pM or less to approximately 2 nM or less, and / or its K+ D At pH 6.0, the concentration is approximately 2 nM or less to approximately 900 pM or less. In some embodiments, the anti-FcRn antibody or antigen-binding fragment binds to the extracellular space and maintains its binding to endosomes when bound. In some embodiments, the anti-FcRn antibody or antigen-binding fragment effectively blocks the binding of one or more autoantibodies to FcRn (e.g., human FcRn), as determined by blocking assays, for example, using cells expressing human FcRn and FACS.

[0177] As used herein, the terms "anti-FcRn antibody" or "antibody specifically bound to FcRn" refer to any form of antibody or antigen-binding fragment specifically bound to FcRn, determined, for example, by surface plasmon resonance (e.g., human FcRn immobilized surface plasmon resonance), at pH 6.0 or pH 7.4 with a K+ concentration below 2 nM. D The bound antibody or its antigen-binding fragment. The term encompasses monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, and biologically functional fragments, as long as they specifically bind to FcRn.

[0178] In some embodiments of the treatments, uses, and compositions disclosed herein, the anti-FcRn antibody or antigen-binding fragment comprises:

[0179] ● A CDR1 containing an amino acid sequence that is identical to 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 amino acid sequence shown in SEQ ID No. 1, 4, 7, or 10;

[0180] ● A CDR2 comprising an amino acid sequence that is identical to 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 amino acid sequence shown in SEQ ID 2, 5, 8, or 11; and

[0181] ● A CDR3 comprising an amino acid sequence that is identical to 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 amino acid sequence shown in SEQ ID No. 3, 6, 9, or 12.

[0182] In some embodiments of the treatments, uses, and compositions disclosed herein, the anti-FcRn antibody or antigen-binding fragment may comprise one or more amino acid deletions, additions, or substitutions from the amino acid sequence described herein.

[0183] In some embodiments of the treatments, uses, and compositions disclosed herein, anti-FcRn antibodies or antigen-binding fragments may comprise amino acid sequences that are identical to or homologous to the amino acid sequences described herein. The terms "identity" or "homology" refer to the relationship between sequences of two or more polypeptides, determined by comparing such sequences. The term "identity" also refers to the degree of sequence correlation between polypeptides, determined by the number of matches between two or more amino acid residue strings. The percentage of "identity" between two sequences is a function of the number of identical positions shared by the sequences (i.e., percentage of identity equals number of identical positions / total number of positions × 100), taking into account the number of gaps introduced to achieve optimal alignment of the two sequences and the length of each gap. Mathematical algorithms can be used to perform sequence comparisons and determine the percentage of identity between two sequences. For sequence comparisons, typically one sequence serves as a reference sequence, to which the test sequence is compared. When using a sequence comparison algorithm, the test sequence and reference sequence are input into the computer, subsequence coordinates are specified if necessary, and sequence algorithm program parameters are specified. Default program parameters can be used, or alternative parameters can be specified. Next, the sequence comparison algorithm calculates the percentage of sequence similarity between the test sequence and the reference sequence based on program parameters. Alternatively, the amino acid sequences disclosed herein can be further used as "query sequences" to search public databases, for example, to identify related sequences. For instance, such searches can be performed using the BLAST program of Altschul et al. (J. Mol. Biol. 215:403-10, 1990).

[0184] When comparing and aligning against the maximum correspondence within a comparison window and designated region, two sequences are considered "substantially identical" if they have a specified percentage of identical amino acid residues (i.e., 60% identical in a designated region, or, if not specified, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical across the entire sequence), measured by using one of the following sequence comparison algorithms or by manual alignment and visual inspection. Optionally, the identical sequence is present in a region of at least about 10 amino acids, or in a region of about 20, 50, 200, or more amino acids. In some embodiments, the anti-FcRn antibody and antigen-binding fragment described herein comprise at least one amino acid sequence that is 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% identical to the sequence shown in any of SEQ ID NOs: 1-22.

[0185] In some embodiments, the antibody or antigen-binding fragment includes a heavy chain variable region, which comprises:

[0186] ● CDR1 containing the amino acid sequence of SEQ ID No: 1, CDR2 containing the amino acid sequence of SEQ ID No: 2, and CDR3 containing the amino acid sequence of SEQ ID No: 3; or

[0187] ●CDR1 containing the amino acid sequence of SEQ ID No: 7, CDR2 containing the amino acid sequence of SEQ ID No: 8, and CDR3 containing the amino acid sequence of SEQ ID No: 9.

[0188] In some embodiments, the antibody or antigen-binding fragment includes a light chain variable region comprising:

[0189] ● CDR1 containing the amino acid sequence of SEQ ID No: 4, CDR2 containing the amino acid sequence of SEQ ID No: 5, and CDR3 containing the amino acid sequence of SEQ ID No: 6; or

[0190] ●CDR1 containing the amino acid sequence of SEQ ID No: 10, CDR2 containing the amino acid sequence of SEQ ID No: 11, and CDR3 containing the amino acid sequence of SEQ ID No: 12.

[0191] In some implementations, the antibody or antigen-binding fragment includes one or more heavy chain variable regions and one or more light chain variable regions selected from the group consisting of:

[0192] ●The heavy chain variable region comprises CDR1 (HCDR1) containing the amino acid sequence of SEQ ID No: 1, CDR2 (HCDR2) containing the amino acid sequence of SEQ ID No: 2, and CDR3 (HCDR3) containing the amino acid sequence of SEQ ID No: 3; and the light chain variable region comprises CDR1 (LCDR1) containing the amino acid sequence of SEQ ID No: 4, CDR2 (LCDR2) containing the amino acid sequence of SEQ ID No: 5, and CDR3 (LCDR3) containing the amino acid sequence of SEQ ID No: 6; or

[0193] ●The heavy chain variable region comprises CDR1 (HCDR1) containing the amino acid sequence of SEQ ID No: 7, CDR2 (HCDR2) containing the amino acid sequence of SEQ ID No: 8, and CDR3 (HCDR3) containing the amino acid sequence of SEQ ID No: 9; and the light chain variable region comprises CDR1 (LCDR1) containing the amino acid sequence of SEQ ID No: 10, CDR2 (LCDR2) containing the amino acid sequence of SEQ ID No: 11, and CDR3 (LCDR3) containing the amino acid sequence of SEQ ID No: 12.

[0194] In some embodiments, the antibody or antigen-binding fragment includes one or more heavy chain variable regions and / or one or more light chain variable regions, the one or more variable regions comprising one or more amino acid sequences selected from the group consisting of amino acid sequences of SEQ ID No: 13-16.

[0195] In some embodiments, the antibody or antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence of SEQ ID No: 13 or 15 and / or a light chain variable region comprising the amino acid sequence of SEQ ID No: 14 or 16.

[0196] In some implementations, the antibody or antigen-binding fragment includes one or more heavy chain variable regions and one or more light chain variable regions selected from the group consisting of:

[0197] ●The heavy chain variable region containing the amino acid sequence of SEQ ID No: 13 and the light chain variable region containing the amino acid sequence of SEQ ID No: 14; and

[0198] ●The heavy chain variable region containing the amino acid sequence of SEQ ID No: 15 and the light chain variable region containing the amino acid sequence of SEQ ID No: 16.

[0199] As used herein with respect to antibodies, the terms “fragment,” “antibody fragment,” and “antigen-binding fragment” refer to one or more fragments of a full-length antibody that retain the ability to specifically bind to a target antigen (e.g., FcRn) and / or provide the functionality of a full-length antibody (e.g., non-competitively interfering with IgG binding to FcRn). Antigen-binding fragments can also be found in larger macromolecules, such as bispecific, trispecific, and multispecific antibodies, such as biantibodies, triantibodies, and tetraantibodies. Examples of antigen-binding fragments include, but are not limited to, single-chain antibodies, Fab fragments, F(ab′)2 fragments, Fd, scFv, regional antibodies, bispecific antibodies, microantibodies, sterol-regulated binding protein cleavage activation protein (SCAP), chelated recombinant antibodies, triantibodies or biantibodies, intracellular antibodies, nanobodies, and small modular immunopharmaceuticals (SMIPs).

[0200] In some embodiments, the antibody or antigen-binding fragment is a binding region immunoglobulin fusion protein, a camelified antibody, an antibody containing VHH, an IgD antibody, an IgE antibody, an IgM antibody, an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody. In some embodiments, the antibody or antigen-binding fragment comprises a derivative in the antibody constant region. In some embodiments, the antibody or antigen-binding fragment is based on a synthetic antibody having a protein scaffold capable of binding to FcRn.

[0201] In some embodiments, the antigen-binding fragment exhibits properties identical or similar to those of the full-length antibody. Without limitation, the antigen-binding fragment can be generated by any suitable method known in the art. For example, the various antigen-binding fragments described herein can be generated by enzymatic or chemical modification of the full-length antibody, de novo synthesis using recombinant DNA methods (e.g., scFv), or identification using a phage presentation library (see, for example, Pini and Bracci, Curr. Protein Pept. Sci. 1(2):155-69, 2000). The utility (e.g., specificity, binding affinity, activity) of the antigen-binding fragment can be screened in the same manner as for the full-length antibody.

[0202] Additionally, antibodies or antigen-binding fragments with mutations in the variable and / or constant regions can be used in the therapeutic methods, uses, and compositions described herein. Examples of such antibodies or antigen-binding fragments include antibodies with conserved substitutions of amino acid residues in the variable and / or constant regions. As used herein, the term "conservative substitution" refers to substitution with another amino acid residue having properties similar to those of the original amino acid residue. For example, lysine, arginine, and histidine have similar properties due to their basic side chains, and aspartic acid and glutamic acid have similar properties due to their acidic side chains. Furthermore, glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, and tryptophan have similar properties due to their nonpolar side chains, and alanine, valine, leucine, threonine, isoleucine, proline, phenylalanine, and methionine have similar properties due to their nonpolar side chains. Moreover, tyrosine, phenylalanine, tryptophan, and histidine have similar properties due to their aromatic side chains. Therefore, it will be apparent to those skilled in the art that even when amino acid residues are substituted in the group exhibiting similar properties as described above, the properties of the antibody or antigen-binding fragment may not show significant changes.

[0203] Additionally, in some embodiments, the antibody or antigen-binding fragment may be conjugated to another substance (e.g., a therapeutic agent or a detectable marker). Substances that can be conjugated to or combined with the antibody or antigen-binding fragments described herein include, but are not limited to, therapeutic agents generally used to treat autoimmune diseases (e.g., standard care agents, such as any one or more standard care agents described herein and / or incorporated herein by reference); substances capable of inhibiting the activity of FcRn; and portions that can physically associate with the antibody or antigen-binding fragment, for example, to improve its stability and / or retention in circulation, such as in blood, serum, lymph, or other tissues. For example, the antibody or antigen-binding fragment may be associated with a polymer, such as a non-antigenic polymer, such as polyoxyethylene or polyethylene oxide. The weight of suitable polymers will vary significantly. Polymers with a number-average molecular weight in the range of about 200 to about 35,000 (or about 1,000 to about 15,000 and 2,000 to about 12,500) can be used. For example, antibody or antigen-binding fragments can be conjugated to water-soluble polymers, such as hydrophilic polyethylene polymers, such as polyvinyl alcohol and polyvinylpyrrolidone. Non-limiting examples of such polymers include, but are not limited to, polyoxyethylene homopolymers, such as polyethylene glycol (PEG) or polypropylene glycol, polyoxyethylene polyols, copolymers thereof, and block copolymers thereof, provided that the water solubility of the block copolymers is maintained.

[0204] In various embodiments, the antibody or antigen-binding fragment is measured, for example by surface plasmon resonance, at pH 6.0 or pH 7.4 with a K+ of 0.01 nM to 2 nM.D (Dissociation constant) is bound to FcRn.

[0205] Pharmaceutical Composition

[0206] This document also provides pharmaceutical compositions comprising an anti-FcRn antibody or its antigen-binding fragment formulated with at least one pharmaceutically acceptable carrier. The compositions may also contain one or more additional therapeutic agents suitable for treating autoimmune diseases. Methods for formulating pharmaceutical compositions and suitable formulations are known in the art (see, for example, "Remington's Pharmaceutical Sciences", Mack Publishing Co., Easton, PA). Suitable formulations may be determined depending on the route of administration.

[0207] As used herein, a “pharmaceutical composition” means a formulation of an anti-FcRn antibody or its antigen-binding fragment, along with other components suitable for administration to a patient, such as pharmaceutically acceptable carriers and / or excipients. The pharmaceutical compositions provided herein are suitable for in vitro and / or in vivo administration. In some embodiments, the pharmaceutical compositions provided herein are in a form permissible for administration and subsequently providing the intended biological activity and / or therapeutic effect of one or more active ingredients. Preferably, the pharmaceutical compositions provided herein do not contain any additional components that would have unacceptable toxicity to the subject to which the formulation will be administered.

[0208] As used herein, the interchangeable terms "pharmaceutically acceptable carrier" and "physiologically acceptable carrier" refer to a carrier, diluent, or excipient that does not cause significant irritation to the subject and does not eliminate the biological activity and properties of the applied antibody or antigen-binding fragment. Therefore, a pharmaceutically acceptable carrier should be compatible with the active ingredient, such as an antibody or its antigen-binding fragment, and may include physiological saline, sterile water, Ringer's solution, buffered saline, dextran solution, maltodextrin solution, glycerol, ethanol, or mixtures of two or more of these. A pharmaceutically acceptable carrier may also enhance or stabilize the composition, or may be used to facilitate the preparation of the composition. A pharmaceutically acceptable carrier may include other physiologically compatible, known additives, such as antioxidants, buffers, solvents, antibacterial agents, dispersion media, coatings, antibacterial and antifungal agents, isotonics, and absorption delay agents and the like. The carrier may be selected to minimize adverse side effects on the subject and / or to minimize degradation of one or more active ingredients.

[0209] As used herein, the term "excipient" refers to an inert substance added to a pharmaceutical composition to further facilitate the administration of the active ingredient. Formulations intended for parenteral administration may contain, for example, excipients such as sterile water or saline, polyalkylene glycols such as polyethylene glycol, vegetable oils, or hydrogenated naphthalene. Other excipients include, but are not limited to, calcium bicarbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, ethylene-vinyl acetate copolymer particles, and surfactants, including, for example, polysorbate 20.

[0210] In various embodiments of the treatment methods, uses, and compositions disclosed herein, anti-FcRn antibodies, antigen-binding fragments, or pharmaceutical compositions may be administered by a variety of methods known in the art. The route and / or mode of administration may vary depending on the desired outcome. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered orally, intravenously, intramuscularly, intraarterially, intramedullaryly, intradurally, intracardiacly, percutaneously, subcutaneously, intraperitoneally, gastrointestinally, sublingually, or locally. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered orally or parenterally. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered parenterally, such as intravenously or subcutaneously (e.g., by injection or infusion). In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered subcutaneously (e.g., by injection or infusion). In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered as a single or multiple subcutaneous injection. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered as a single (i.e., once) subcutaneous injection. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered via two or more consecutive subcutaneous injections. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered without intravenous administration (e.g., intravenous induction) prior to one or more subcutaneous injections. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is delivered via a syringe, catheter, pump delivery system, or endovascular stent. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is delivered via a syringe (e.g., a pre-filled syringe). Depending on the route of administration, one or more active compounds, i.e., anti-FcRn antibodies or antigen-binding fragments, may be encapsulated in a material to protect the one or more compounds from acids and other natural conditions that may inactivate them.

[0211] Antibodies, antigen-binding fragments, or pharmaceutical compositions can be formulated into various forms, such as powders, tablets, capsules, liquids, injections, ointments, or syrups, and / or contained in single- or multi-dose containers, such as sealed ampoules, vials, or syringes. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated into an injectable form. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated with one or more excipients, diluents, dispersants, surfactants, binders, and / or lubricants to form an aqueous solution, suspension, or emulsion. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is contained in a syringe (e.g., a pre-filled syringe). In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is contained in a syringe having a small-gauge needle (e.g., needles larger than about 25, about 26, about 27, about 28, about 29, and / or about 30 gauge) and / or a syringe compatible with small-gauge needles.

[0212] In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated to achieve stability and / or prevent or minimize physical and / or chemical degradation prior to administration. Physical instability may involve processes such as denaturation and aggregation, while common chemical degradation pathways include, but are not limited to, cross-linking, deamidation, isomerization, oxidation, and fragmentation (see, for example, Wang et al., J. Pharm. Sci. 91(1):1-26, 2007). As used herein, when used to describe an antibody or its antigen-binding fragment, the term “stable” or “well-defined” means that the antibody or antigen-binding fragment remains intact in a manner that preserves its activity (e.g., binding to FcRn) and / or achieves a therapeutic effect. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated with one or more pharmaceutically acceptable carriers (e.g., one or more excipients) to make it stable under standard storage conditions. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated with one or more pharmaceutically acceptable carriers (e.g., one or more excipients) to make it stable at high concentrations. In some embodiments, the antibody or antigen-binding fragment may be stably concentrated in a formulation of up to about 150 mg / mL or more. In some embodiments, the antibody or antigen-binding fragment may be stably concentrated in a formulation of up to about 170 mg / mL or more. In some embodiments, the antibody or antigen-binding fragment may be stably concentrated in a formulation of a concentration higher than about 170 mg / mL (e.g., about 180 mg / mL, about 200 mg / mL, about 220 mg / mL or more). In some embodiments, the stably concentrated formulation (e.g., a formulation containing up to about 170 mg / mL or more of antibody or antigen-binding fragment) maintains an acceptable viscosity for administration via a small-gauge needle. In some embodiments, the small-gauge needle is larger than about 25, about 26, about 27, about 28, about 29, or about 30 gauge.

[0213] Anti-FcRn antibodies or antigen-binding fragments can be formulated into pharmaceutically acceptable dosage forms using methods known to those skilled in the art. For example, parenteral compositions can be formulated into unit dosage forms for ease of administration and uniform dosage. As used herein, a “unit dosage form” refers to a physically discrete unit suitable as a unit dose for use on a subject to be treated; each unit contains a predetermined amount of active compound bound to a pharmaceutically acceptable carrier, calculated to produce the desired therapeutic effect. In some embodiments, antibodies, antigen-binding fragments, or pharmaceutical compositions are formulated into unit dosage forms. In some embodiments, antibodies, antigen-binding fragments, or pharmaceutical compositions are formulated into unit dosage forms for subcutaneous administration. In some embodiments, antibodies, antigen-binding fragments, or pharmaceutical compositions are formulated into unit dosage forms for administration in the form of one or more subcutaneous injections (e.g., a single subcutaneous injection or two or more consecutive subcutaneous injections). In some embodiments, antibodies, antigen-binding fragments, or pharmaceutical compositions are formulated into unit dosage forms (e.g., in the form of one or more subcutaneous injections) for self-administration by a patient and / or administration by a treating clinician.

[0214] How to use

[0215] This document provides methods for improving anti-FcRn therapy, comprising administering the antibodies or antigen-binding fragments thereof provided herein. In some embodiments, this document provides methods for treating autoimmune diseases (e.g., GD, RA, TED, MG, CIDP, etc.) in subjects via a dosing regimen of anti-FcRn therapy (e.g., batolizumab or IMVT-1402). Autoimmune diseases treatable with the anti-FcRn therapy described herein include, but are not limited to, Graves' disease (GD), thyroid ophthalmopathy (TED), rheumatoid arthritis (RA), myasthenia gravis (MG), immune thrombocytopenic purpura, pemphigus vulgaris, chronic inflammatory demyelinating polyneuropathy (CIDP), and systemic lupus erythematosus (SLE). In some embodiments, the autoimmune disease is a progressive autoimmune disease. Autoimmune diseases are characterized by progressiveness, where symptoms worsen or exacerbate over time, with or without treatment.

[0216] Dosage regimen for Graves' disease (GD)

[0217] In some aspects, this disclosure provides compositions and methods for treating Graves' disease. In some embodiments, the method includes a dosing regimen for GD (e.g., dosage, dosing frequency, etc.) that improves therapeutic efficacy (e.g., relative to using a different dosing regimen).

[0218] Graves' disease (GD) is an autoimmune condition in which autoantibodies bind to thyroid cells, mimicking thyroid-stimulating hormone (TSH). In some embodiments, the autoantibodies binding to thyroid cells (e.g., thyroid-stimulating hormone receptor (THSR; also known as thyroid-stimulating hormone) autoantibodies (TRAb)) induce excessive production of thyroid hormone, leading to inflammation and goiter, and can cause systemic symptoms, including irregular heart rate, pretibial myxedema, weight loss, muscle weakness, temperature sensitivity, and other symptoms. In some embodiments, the TRAb contains thyroid-stimulating immunoglobulin (TSI) and can be measured using a suitable TSI assay. GD is chronic and can negatively impact life expectancy if left untreated. Assays used to determine the onset and severity of GD are known in the art (see, for example, Ehlers et al. Graves, disease in clinical perspective. Front Biosci, 2019. 24(1): 33-45).

[0219] Hyperthyroidism is often initially suspected when a subject presents with low baseline serum TSH levels. The normal range for TSH is 0.5 to 5.0 mU / L. Diagnostic accuracy is improved by assessing blood levels of thyroxine (T4) and triiodothyronine (T3), as an elevation in one or both can further confirm the diagnosis of hyperthyroidism. In some embodiments, the normal range for total T4 in adults is 5.0 to 12.0 μg / dL. In some embodiments, the normal level for free T4 (FT4) is 0.7 to 1.9 ng / dL. In some embodiments, the normal level for total T3 in adults is 79 to 165 ng / dL. Therefore, the upper limit of normal (ULN) for free T4 (FT4) is considered to be approximately 1.9 ng / dL, and the ULN for total T3 is considered to be approximately 165 ng / dL. TSH, T3, and T4 levels are typically determined by electrochemiluminescence immunoassay or enzyme-linked immunosorbent assay (ELISA), but can be measured by any suitable assay.

[0220] In some embodiments, this disclosure provides compositions (e.g., anti-FcRn antibody IMVT-1402 or battolimab) and methods (e.g., dosing regimens) for treating GD in subjects. In some embodiments, an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) in the range of 550 to 700 mg is administered to the subject once weekly. In some embodiments, an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) in the range of 550 to 700 mg is administered to the subject once weekly. In some embodiments, an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) in the range of 550 to 700 mg is administered to the subject once weekly for 20 to 60 weeks.

[0221] In some implementations, the following ranges of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) are administered to the subject once weekly: 550 to 700 mg, 550 to 690 mg, 550 to 680 mg, 550 to 670 mg, 550 to 660 mg, 550 to 650 mg, 550 to 640 mg, 550 to 630 mg, 550 to 620 mg, 550 to 610 mg, 550 to 600 mg, 550 to 590 mg, 550 to 580 mg, 550 to 570 mg, 550 to 560 mg, 580 to 700 mg, 580 to 690 mg, 580 to 680 mg, 580 to 670 mg, 580 to 660 mg, 580 to 650 mg, 580 to 640 mg, 580 to 630 mg. mg, 580 to 620 mg, 580 to 610 mg, 580 to 600 mg, 580 to 590 mg, 600 to 700 mg, 600 to 690 mg, 600 to 680 mg, 600 to 670 mg, 600 to 660 mg, 600 to 650 mg, 600 to 640 mg, 600 to 630 mg, 600 to 620 mg, 600 to 610 mg, 620 to 700 mg, 620 to 690 mg, 620 to 680 mg, 620 to 670 mg, 620 to 660 mg, 620 to 650 mg, 620 to 640 mg, 620 to 630 mg, 650 to 700 mg, 650 to 690 mg, 650 to 680 mg, 650 to 670 mg, 650 to 660 mg mg, 680 to 700 mg or 680 to 690 mg.In some implementations, IMVT-1402 is administered once weekly to subjects with or suspected of having GD in the following ranges: 550 to 700 mg, 550 to 690 mg, 550 to 680 mg, 550 to 670 mg, 550 to 660 mg, 550 to 650 mg, 550 to 640 mg, 550 to 630 mg, 550 to 620 mg, 550 to 610 mg, 550 to 600 mg, 550 to 590 mg, 550 to 580 mg, 550 to 570 mg, 550 to 560 mg, 580 to 700 mg, 580 to 690 mg, 580 to 680 mg, 580 to 670 mg, 580 to 660 mg, 580 to 650 mg, 580 to 640 mg, 580 to 630 mg, 580 to 620 mg. mg, 580 to 610 mg, 580 to 600 mg, 580 to 590 mg, 600 to 700 mg, 600 to 690 mg, 600 to 680 mg, 600 to 670 mg, 600 to 660 mg, 600 to 650 mg, 600 to 640 mg, 600 to 630 mg, 600 to 620 mg, 600 to 610 mg, 620 to 700 mg, 620 to 690 mg, 620 to 680 mg, 620 to 670 mg, 620 to 660 mg, 620 to 650 mg, 620 to 640 mg, 620 to 630 mg, 650 to 700 mg, 650 to 690 mg, 650 to 680 mg, 650 to 670 mg, 650 to 660 mg, 680 to 700 mg mg or 680 to 690 mg. In some embodiments, IMVT-1402 is administered to the subject once weekly at a dose of 600 mg.In some implementations, battolimab is administered once weekly to subjects with or suspected of having GD in the following ranges: 550 to 700 mg, 550 to 690 mg, 550 to 680 mg, 550 to 670 mg, 550 to 660 mg, 550 to 650 mg, 550 to 640 mg, 550 to 630 mg, 550 to 620 mg, 550 to 610 mg, 550 to 600 mg, 550 to 590 mg, 550 to 580 mg, 550 to 570 mg, 550 to 560 mg, 580 to 700 mg, 580 to 690 mg, 580 to 680 mg, 580 to 670 mg, 580 to 660 mg, 580 to 650 mg, 580 to 640 mg, 580 to 630 mg, 580 to 620 mg. mg, 580 to 610 mg, 580 to 600 mg, 580 to 590 mg, 600 to 700 mg, 600 to 690 mg, 600 to 680 mg, 600 to 670 mg, 600 to 660 mg, 600 to 650 mg, 600 to 640 mg, 600 to 630 mg, 600 to 620 mg, 600 to 610 mg, 620 to 700 mg, 620 to 690 mg, 620 to 680 mg, 620 to 670 mg, 620 to 660 mg, 620 to 650 mg, 620 to 640 mg, 620 to 630 mg, 650 to 700 mg, 650 to 690 mg, 650 to 680 mg, 650 to 670 mg, 650 to 660 mg, 680 to 700 mg mg or 680 to 690 mg. In some implementations, battolimab is administered once weekly at a dose of 680 mg to subjects with or suspected of having GD.

[0222] In some implementations, subjects with or suspected of having GD are given an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) at a dose ranging from 550 to 700 mg (e.g., any dose described herein) once weekly for 20 to 60 weeks, 20 to 58 weeks, 20 to 55 weeks, 20 to 52 weeks, 20 to 50 weeks, 20 to 45 weeks, 20 to 42 weeks, 20 to 40 weeks, 20 to 35 weeks, 20 to 30 weeks, 20 to 25 weeks, 25 to 60 weeks, 25 to 58 weeks, 25 to 55 weeks, 25 to 52 weeks, 25 to 50 weeks, 25 to 45 weeks, 25 to 42 weeks, 25 to 40 weeks, 25 to 35 weeks, 25 to 30 weeks, 30 to 60 weeks, 30 to 58 weeks, 30 to 55 weeks, 30 to 55 weeks, 30 to 60 weeks, 30 to 58 ...8 weeks, 30 to 60 weeks, 30 to 60 weeks, 30 to 60 weeks, 30 to 60 weeks, 30 to 60 weeks, 30 to 60 52 weeks, 30 to 50 weeks, 30 to 45 weeks, 30 to 42 weeks, 30 to 40 weeks, 30 to 35 weeks, 35 to 60 weeks, 35 to 58 weeks, 35 to 55 weeks, 35 to 52 weeks, 35 to 50 weeks, 35 to 45 weeks, 35 to 42 weeks, 35 to 40 weeks, 40 to 60 weeks, 40 to 58 weeks, 40 to 55 weeks, 40 to 52 weeks, 40 to 50 weeks, 40 to 45 weeks, 40 to 42 weeks, 45 to 60 weeks, 45 to 58 weeks, 45 to 55 weeks, 45 to 52 weeks, 45 to 50 weeks, 50 to 60 weeks, 50 to 58 weeks, 50 to 55 weeks, 50 to 52 weeks, 55 to 60 weeks, or 55 to 58 weeks.

[0223] In some embodiments, IMVT-1402 is administered to the subject. In some embodiments, 600 mg of IMVT-1402 is administered to the subject once weekly for 26 weeks. In some embodiments, 600 mg of IMVT-1402 is administered to the subject once weekly for 52 weeks.

[0224] In some embodiments, battolimab is administered to the subject. In some embodiments, 680 mg of battolimab is administered to the subject once weekly for 26 weeks. In some embodiments, 680 mg of battolimab is administered to the subject once weekly for 26 weeks, followed by 340 mg of battolimab once weekly for another 26 weeks. In some embodiments, 680 mg of battolimab is administered to the subject once weekly for 52 weeks.

[0225] In some embodiments, a subject with Graves' disease (GD) is given 300 mg of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) once weekly indefinitely. In some embodiments, a subject with GD is given 600 mg or 680 mg of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) once weekly indefinitely. In some embodiments, a subject with GD is given 300 mg of IMVT-1402 once weekly indefinitely. In some embodiments, a subject with GD is given 600 mg of IMVT-1402 once weekly indefinitely. In some embodiments, a subject with GD is given 340 mg of battolimab once weekly indefinitely. In some embodiments, a subject with GD is given 680 mg of battolimab once weekly indefinitely.

[0226] In some implementations, the subject has hyperthyroidism prior to administration. Hyperthyroidism is further subdivided into two types: (i) marked hyperthyroidism, in which total T3 and / or free T4 are greater than ULN and TSH levels are lower than LLN; and (ii) subclinical hyperthyroidism, in which T3 and free T4 are within the normal range (WNL) and TSH levels are lower than LLN (see Ross et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 26(1)).

[0227] In some embodiments, the subject had significant hyperthyroidism prior to administration. In some embodiments, prior to administration, the baseline T3 level of GD subjects with significant hyperthyroidism was higher than the T3 ULN (e.g., greater than 1×ULN, greater than 2×ULN, greater than 3×ULN, greater than 4×ULN, greater than 5×ULN, greater than 6×ULN, greater than 7×ULN, greater than 8×ULN, greater than 9×ULN, greater than 10×ULN, greater than 15×ULN, greater than 20×ULN, greater than 50×ULN, greater than 100×ULN, or higher). In some embodiments, prior to administration, the baseline T3 level of GD subjects with significant hyperthyroidism was higher than the T3 ULN. (For example, baseline T3 is in the following ranges: 1.1× to 1000×ULN, 1.1× to 900×ULN, 1.1× to 800×ULN, 1.1× to 700×ULN, 1.1× to 600×ULN, 1.1× to 500×ULN, 1.1× to 400×ULN, 1.1× to 300×ULN, 1.1× to 200×ULN, 1.1× to 100×ULN, 1.1× to 100×ULN, 1.1× to 25×ULN, 1.1× to 10×ULN, 1.1× to 5×ULN, 1.1× to 3×ULN, 1.1× to 2×ULN, 1.5× to 1000×ULN, 1.5× to 900×ULN, 1.5× to 800×ULN, 1.5× to 700×ULN, 1.5× to 600×ULN, 1.5× to 500×ULN, 1.5× to 400×ULN, 1.5× to 300×ULN, 1.5× to 200×ULN, 1.5× to 100×ULN, 1.5× to 100×ULN, 1.5× to 25×ULN, 1.5 × to 10×ULN, 1.5× to 5×ULN, 1.5× to 3×ULN, 1.5× to 2×ULN, 1.5× to 1000×ULN, 1.5× to 900×ULN, 1.5× to 800×ULN, 1.5× to 700×ULN, 1.5× to 600×ULN, 1.5× to 500×ULN, 1.5× to 400×ULN, 1.5× to 300×ULN, 1.5× to 200×ULN, 1.5× to 100×ULN, 1.5× to 100×ULN, 1 0.5× to 25×ULN, 1.5× to 10×ULN, 1.5× to 5×ULN, 1.5× to 3×ULN, 1.5× to 2×ULN, 2× to 1000×ULN, 2× to 900×ULN, 2× to 800×ULN, 2× to 700×ULN, 2× to 600×ULN, 2× to 500×ULN, 2× to 400×ULN, 2× to 300×ULN, 2× to 200×ULN, 2× to 100×ULN, 2× to 100×ULN, 2× to 25×ULN2× to 10×ULN, 2× to 5×ULN, 2× to 3×ULN, 5× to 1000×ULN, 5× to 900×ULN, 5× to 800×ULN, 5× to 700×ULN, 5× to 600×ULN, 5× to 500×ULN, 5× to 400×ULN, 5× to 300×ULN, 5× to 200×ULN, 5× to 100×ULN, 5× to 100×ULN, 5× to 25×ULN, 5× to 10×ULN, 10× to 1000×ULN, 10× to 900×ULN, 10× to 800×ULN, 10× to 700×ULN, 10× to 600×ULN, 10× to 500×ULN, 10× to 400×ULN, 10× to 300×ULN, 10× to 200×ULN, 10× to 100×ULN, 10× to 100×ULN, 10× to 20×ULN, 100× to 1000×ULN, 100× to 900×ULN, 100× to 800×ULN, 100× to 700×ULN, 100× to 60 0×ULN, 100× to 500×ULN, 100× to 400×ULN, 100× to 300×ULN, 100× to 200×ULN, 100× to 1000×ULN, 100× to 900×ULN, 100× to 800×ULN, 100× to 700×ULN, 100× to 600×ULN, 100× to 500×ULN, 100× to 400×ULN, 100× to 300×ULN, 100× to 200×ULN, 250× to 1000×ULN LN, 250× to 900×ULN, 250× to 800×ULN, 250× to 700×ULN, 250× to 600×ULN, 250× to 500×ULN, 250× to 400×ULN, 500× to 1000×ULN, 500× to 900×ULN, 500× to 800×ULN, 500× to 700×ULN, 500× to 600×ULN, 750× to 1000×ULN, 750× to 900×ULN, 750× to 800×ULN). In some embodiments, prior to administration, the baseline FT4 level of GD subjects with significant hyperthyroidism was higher than the FT4 ULN (e.g., greater than 1×ULN, greater than 2×ULN, greater than 3×ULN, greater than 4×ULN, greater than 5×ULN, greater than 6×ULN, greater than 7×ULN, greater than 8×ULN, greater than 9×ULN, greater than 10×ULN, greater than 15×ULN, greater than 20×ULN, greater than 50×ULN, greater than 100×ULN, or higher). In some embodiments, prior to administration, the baseline FT4 level of GD subjects with significant hyperthyroidism was higher than the FT4 ULN (e.g., within the range of 1.1× to 1000×ULN).1.1× to 900×ULN, 1.1× to 800×ULN, 1.1× to 700×ULN, 1.1× to 600×ULN, 1.1× to 500×ULN, 1.1× to 400×ULN, 1.1× to 300×ULN, 1.1× to 200×ULN, 1.1× to 100×ULN, 1.1× to 100×ULN, 1.1× to 25×ULN, 1.1× to 10×ULN, 1.1× to 5×ULN, 1.1× to 3×ULN, 1.1× to 2×ULN, 1.5× to 1000×ULN, 1.5× to 900×ULN, 1.5× to 800×ULN, 1.5× to 700×ULN, 1.5× to 600×ULN LN, 1.5× to 500×ULN, 1.5× to 400×ULN, 1.5× to 300×ULN, 1.5× to 200×ULN, 1.5× to 100×ULN, 1.5× to 100×ULN, 1.5× to 25×ULN, 1.5× to 10×ULN, 1.5× to 5×ULN, 1.5× to 3×ULN, 1.5× to 2×ULN, 1.5× to 1000×ULN, 1.5× to 900×ULN, 1.5× to 800×ULN, 1.5× to 700×ULN, 1.5× to 600×ULN, 1.5× to 500×ULN, 1.5× to 400×ULN, 1.5× to 300×ULN, 1.5× to 20 0×ULN, 1.5× to 100×ULN, 1.5× to 100×ULN, 1.5× to 25×ULN, 1.5× to 10×ULN, 1.5× to 5×ULN, 1.5× to 3×ULN, 1.5× to 2×ULN, 2× to 1000×ULN, 2× to 900×ULN, 2× to 800×ULN, 2× to 700×ULN, 2× to 600×ULN, 2× to 500×ULN, 2× to 400×ULN, 2× to 300×ULN, 2× to 200×ULN, 2× to 100×ULN, 2× to 100×ULN, 2× to 25×ULN, 2× to 10×ULN, 2× to 5×ULN, 2× to 3×ULN, 5 × to 1000×ULN, 5× to 900×ULN, 5× to 800×ULN, 5× to 700×ULN, 5× to 600×ULN, 5× to 500×ULN, 5× to 400×ULN, 5× to 300×ULN, 5× to 200×ULN, 5× to 100×ULN, 5× to 100×ULN, 5× to 25×ULN, 5× to 10×ULN, 10× to 1000×ULN, 10× to 900×ULN, 10× to 800×ULN, 10× to 700×ULN, 10× to 600×ULN, 10× to 500×ULN, 10× to 400×ULN, 10× to 300×ULN, 10× to 200×ULN10× to 100×ULN, 10× to 100×ULN, 10× to 20×ULN, 100× to 1000×ULN, 100× to 900×ULN, 100× to 800×ULN, 100× to 700×ULN, 100× to 600×ULN, 100× to 500×ULN, 100× to 400×ULN, 100× to 300×ULN, 100× to 200×ULN, 100× to 1000×ULN, 100× to 900×ULN, 100× to 800×ULN, 100× to 700×ULN, 100× to 600×ULN, 100× to 500×ULN, 100 × to 400×ULN, 100× to 300×ULN, 100× to 200×ULN, 250× to 1000×ULN, 250× to 900×ULN, 250× to 800×ULN, 250× to 700×ULN, 250× to 600×ULN, 250× to 500×ULN, 250× to 400×ULN, 500× to 1000×ULN, 500× to 900×ULN, 500× to 800×ULN, 500× to 700×ULN, 500× to 600×ULN, 750× to 1000×ULN, 750× to 900×ULN, 750× to 800×ULN). In some embodiments, prior to administration, the baseline TSH level of GD subjects with significant hyperthyroidism is lower than TSH LLN (e.g., less than 1×LLN, less than 0.9×LLN, less than 0.8×LLN, less than 0.7×LLN, less than 0.6×LLN, less than 0.5×LLN, less than 0.4×LLN, less than 0.3×LLN, less than 0.2×LLN, less than 0.1×LLN, less than 0.075×LLN, less than 0.05×LLN, less than 0.025×LLN, less than 0.01×LLN or lower). In some embodiments, prior to administration, the baseline TSH level of GD subjects with significant hyperthyroidism is lower than TSH LLN. (For example, within the following ranges: 0.001× to 0.99×LLN, 0.005× to 0.99×LLN, 0.0008× to 0.99×LLN, 0.01× to 0.99×LLN, 0.05× to 0.99×LLN, 0.08× to 0.99×LLN, 0.1× to 0.99×LLN, 0.2× to 0.99×LLN, 0.3× to 0. 0.99×LLN, 0.4× to 0.99×LLN, 0.5× to 0.99×LLN, 0.6× to 0.99×LLN, 0.7× to 0.99×LLN, 0.8× to 0.99×LLN, 0.9× to 0.99×LLN, 0.001× to 0.8×LLN, 0.005× to 0.8×LLN, 0.0008× to 0.8×LLN,0.01× to 0.8×LLN, 0.05× to 0.8×LLN, 0.08× to 0.8×LLN, 0.1× to 0.8×LLN, 0.2× to 0.8×LLN, 0.3× to 0.8×LLN, 0.4× to 0.8×LLN, 0.5× to 0.8×LLN, 0.6× to 0.8×LLN, 0.7× to 0.8×LLN, 0.001× to 0.5×LLN, 0.005× to 0.5×LLN, 0.0008× to 0.5×L LN, 0.01× to 0.5×LLN, 0.05× to 0.5×LLN, 0.08× to 0.5×LLN, 0.1× to 0.5×LLN, 0.2× to 0.5×LLN, 0.3× to 0.5×LLN, 0.4× to 0.5×LLN, 0.001× to 0.3×LLN, 0.005× to 0.3×LLN, 0.0008× to 0.3×LLN, 0.01× to 0.3×LLN, 0.05× to 0.3×LLN, 0.08× Up to 0.3×LLN, 0.1× to 0.3×LLN, 0.2× to 0.3×LLN, 0.001× to 0.1×LLN, 0.005× to 0.1×LLN, 0.0008× to 0.1×LLN, 0.01× to 0.1×LLN, 0.05× to 0.1×LLN, 0.08× to 0.1×LLN, 0.001× to 0.075×LLN, 0.005× to 0.075×LLN, 0.0008× to 0.075×LLN, 0 0.01× to 0.075×LLN, 0.05× to 0.075×LLN, 0.08× to 0.075×LLN, 0.001× to 0.05×LLN, 0.005× to 0.05×LLN, 0.0008× to 0.05×LLN, 0.01× to 0.05×LLN, 0.001× to 0.02×LLN, 0.005× to 0.02×LLN, 0.0008× to 0.02×LLN or 0.01× to 0.02×LLN).

[0228] In some embodiments, the subject had subclinical hyperthyroidism prior to administration. In some embodiments, the T3 and FT4 levels of the GD subject with subclinical hyperthyroidism were within the normal range prior to administration. In some embodiments, the TSH level of the GD subject with subclinical hyperthyroidism was less than 0.1 mU / L prior to administration (e.g., TSH levels less than 0.1 mU / L, less than 0.09 mU / L, less than 0.08 mU / L, less than 0.07 mU / L, less than 0.06 mU / L, less than 0.05 mU / L, less than 0.04 mU / L, less than 0.03 mU / L, less than 0.02 mU / L, less than 0.01 mU / L, less than 0.0075 mU / L, less than 0.005 mU / L, less than 0.002 mU / L, less than 0.001 mU / L or lower). In some implementations, prior to administration, the TSH level in GD subjects with subclinical hyperthyroidism was less than 0.1 mU / L (e.g., within the following ranges: 0.001 to 0.1 mU / L, 0.001 to 0.1 mU / L, 0.001 to 0.1 mU / L, 0.001 to 0.1 mU / L, 0.001 to 0.1 mU / L, 0.001 to 0.1 mU / L, 0.001 to 0.1 mU / L, 0.001 to 0.09 mU / L, 0.001 to 0.08 mU / L, 0.001 to 0.07 mU / L, 0.001 to 0.06 mU / L, 0.001 to 0.05 mU / L, 0.001 to 0.04 mU / L, 0.001 to 0.03 mU / L). mU / L, 0.001 to 0.02 mU / L, 0.001 to 0.01 mU / L, 0.001 to 0.009 mU / L, 0.001 to 0.008 mU / L, 0.001 to 0.007 mU / L, 0.001 to 0.006 mU / L, 0.001 to 0.005 mU / L, 0.001 to 0.004mU / L, 0.001 to 0.003 mU / L, 0.001 to 0.002 mU / L, 0.005 to 0.1 mU / L, 0.005 to 0.1 mU / L, 0.005 to 0.1 mU / L, 0.005 to 0.1 mU / L, 0.005 to 0.1 mU / L, 0.005 to 0.1 mU / L, 0.005 to 0.1mU / L, 0.005 to 0.09 mU / L, 0.005 to 0.08 mU / L, 0.005 to 0.07 mU / L, 0.005 to 0.06 mU / L, 0.005 to 0.05 mU / L, 0.005 to 0.04 mU / L, 0.005 to 0.03 mU / L, 0.005 to 0.02 mU / L, 0.005 to 0.01 mU / L, 0.005 to 0.009 mU / L, 0.005 to 0.008 mU / L, 0.005 to 0.007 mU / L, 0.005 to 0.006mU / L, 0.008 to 0.1 mU / L, 0.008 to 0.1 mU / L, 0.008 to 0.1 mU / L, 0.008 to 0.1 mU / L, 0.008 to 0.1 mU / L, 0.008 to 0.1 mU / L, 0.008 to 0.1 mU / L, 0.008 to 0.09 mU / L, 0.008 to 0.08 mU / L, 0.008 to 0.07 mU / L, 0.008 to 0.06 mU / L, 0.008 to 0.05 mU / L, 0.008 to 0.04 mU / L, 0.008 to 0.03 mU / L, 0.008 to 0.02 mU / L, 0.008 to 0.01 mU / L, 0.008 to 0.009 mU / L, 0.01 to 0.1 mU / L, 0.01 to 0.1 mU / L, 0.01 to 0.1 mU / L, 0.01 to 0.1 mU / L, 0.01 to 0.1 mU / L, 0.01 to 0.1 mU / L, 0.01 to 0.1 mU / L, 0.01 to 0.09 mU / L, 0.01 to 0.08 mU / L, 0.01 to 0.07 mU / L, 0.01 to 0.06 mU / L, 0.01 to 0.05 mU / L, 0.01 to 0.04 mU / L, 0.01 to 0.03 mU / L, 0.01 to 0.02 mU / L, 0.05 to 0.1mU / L, 0.05 to 0.1 mU / L, 0.05 to 0.1 mU / L, 0.05 to 0.1 mU / L, 0.05 to 0.1 mU / L, 0.05 to 0.1mU / L, 0.05 to 0.1 mU / L, 0.05 to 0.09 mU / L, 0.05 to 0.08 mU / L, 0.05 to 0.07 mU / L, 0.05 to 0.06 mU / L, 0.08 to 0.1 mU / L or 0.08 to 0.1 mU / L). .

[0229] The presence of an autoantibody against the thyroid-stimulating hormone receptor (TSHR) (TRAb) is highly specific for glomerular dysplasia (GD). In some embodiments, the TRAb levels in subjects with GD are elevated prior to administration. In some embodiments, the normal range for TRAb is 0 to 0.9 IU / L.

[0230] Approximately 20% to 25% of individuals with Graves' disease (GD) also have thyroid eye disease (TED), also known as Graves' ophthalmopathy, and 80% of GD patients with TED develop TED within 18 months of GD onset. TED affects the extraocular muscles and posterior adipose tissue. In some embodiments, individuals with GD have one or more TED symptoms, including blurred or diplopia, changes in eye appearance (e.g., bulging), difficulty moving the eyes, low tolerance to bright light, eye pain and / or redness, and eyelid swelling or fullness. The development of TED symptoms is typically progressive within the first year after onset, and severe TED may require treatment with steroids and / or orbital radiation therapy. In some embodiments, individuals with GD may have one or more ocular symptoms but are not diagnosed with TED. In some embodiments, a subject has GD but does not have any ocular symptoms. In some embodiments, a subject has GD but is not diagnosed with TED. In some embodiments, a subject has GD but does not have any ocular symptoms and is not diagnosed with TED. In some embodiments, the anti-FcRn therapies described herein (e.g., battolimab or IMVT-1402) prevent or delay the onset or development of TED relative to subjects not receiving anti-FcRn therapy. In some embodiments, improvement in TED symptoms indicates a positive response to the anti-FcRn therapies described herein (e.g., battolimab or IMVT-1402). In some embodiments, administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) prevents TED onset in subjects with GD. In some embodiments, administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) delays TED onset in subjects with GD for one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, twelve months, fifteen months, eighteen months, two years, three years, four years, five years, or longer. In some embodiments, administration of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) reduces or eliminates one or more ocular symptoms in a subject with Graves' disease (GD). In some embodiments, administration of an anti-FcRn antibody as described herein reduces bulging of the eye relative to the state before administration. In some embodiments, administration of an anti-FcRn antibody reduces the eyelid aperture of the subject relative to the state before administration. In some embodiments, administration of an anti-FcRn antibody reduces the thyroid volume of the subject relative to the state before administration.

[0231] In some embodiments, anti-FcRn therapy (e.g., batopilimab or IMVT-1402) induces GD remission in the treated subject. Subjects are generally considered to be in GD remission when they have normal thyroid function for at least 6 months or longer after discontinuing ATD therapy; for subjects receiving both anti-FcRn and ATD therapy, subjects are considered to be in remission when they have maintained normal thyroid function for at least 6 months or longer after discontinuing both therapies. In some embodiments, administration of an anti-FcRn antibody (e.g., IMVT-1402 or batopilimab) using the dosing regimen described herein induces remission in the subject, and the subject maintains remission for at least six months, at least one year, at least two years, at least three years, at least four years, at least five years, or longer.

[0232] In some embodiments, subjects with GD receiving the anti-FcRn antibody dosing regimen described herein have previously been treated with one or more antithyroid drugs (ATDs). In some embodiments, subjects with GD have received an ATD for more than 3 months prior to administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab). In some embodiments, subjects with GD are receiving an ATD at the time of receiving the anti-FcRn antibody dosing regimen described herein. Non-limiting examples of ATDs include methimazole, carbimazole, or propylthiouracil. In some embodiments, subjects with GD have received a dose of at least 20 mg / day of methimazole (e.g., at least four weeks prior to baseline assessment). In some embodiments, subjects with GD have received a dose of at least 30 mg / day of carbimazole (e.g., at least four weeks prior to baseline assessment). In some embodiments, subjects with GD have received a dose of at least 200 mg / day of propylthiouracil (e.g., at least four weeks prior to baseline assessment). In some embodiments, subjects with GD have received an anti-ATD for at least six months prior to baseline assessment and before initiating treatment with an anti-FcRn antibody (e.g., IMVT-1402 or battolimumab). In some embodiments, subjects with GD have received at least 15 mg / day of methimazole (e.g., at any point in their treatment history) prior to baseline assessment and before initiating treatment with an anti-FcRn antibody (e.g., IMVT-1402 or battolimumab). In some embodiments, subjects with GD have received at least 20 mg / day of carbimazole (e.g., at any point in their treatment history) prior to baseline assessment and before initiating treatment with an anti-FcRn antibody (e.g., IMVT-1402 or battolimumab). In some embodiments, subjects with GD have received at least 150 mg / day of propylthiouracil (e.g., at any point in their treatment history) prior to baseline assessment and before initiating treatment with an anti-FcRn antibody (e.g., IMVT-1402 or battolimumab). In some embodiments, subjects with GD are receiving at least 10 mg / day of methimazole (e.g., at baseline assessment) before initiating treatment with an anti-FcRn antibody (e.g., IMVT-1402 or battolimab). In some embodiments, subjects with GD are receiving at least 15 mg / day of carbimazole (e.g., at baseline assessment) before initiating treatment with an anti-FcRn antibody (e.g., IMVT-1402 or battolimab). In some embodiments, subjects with GD are receiving at least 100 mg / day of propylthiouracil (e.g., at baseline assessment) before initiating treatment with an anti-FcRn antibody (e.g., IMVT-1402 or battolimab).

[0233] In some embodiments, the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimens described herein are more suitable for subjects with Graves' disease (GD) but without certain symptoms or comorbidities. For example, in some embodiments, the subject with GD has not previously been treated with radioactive iodine (RAI) therapy. In some embodiments, the subject with GD has not undergone total thyroidectomy. In some embodiments, the subject with GD does not have T3 and / or FT4 below LLN prior to initiating anti-FcRn antibody (e.g., IMVT-1402 or battolimab) administration. In some embodiments, the subject with GD has not received any dose of levothyroxine, dried thyroid extract, or T3 within 6 weeks prior to baseline assessment prior to initiating treatment with anti-FcRn antibody (e.g., IMVT-1402 or battolimab). In some embodiments, the subject with GD has not received blockade-blockade and replacement therapy. In some embodiments, subjects with GD do not have a history of hyperthyroidism (e.g., toxic adenoma or toxic multinodular goiter) and / or thyroid storm within 6 months prior to baseline assessment before initiating treatment with an anti-FcRn antibody (e.g., IMVT-1402 or battolimab). In some embodiments, subjects with GD do not have a known active autoimmune disease requiring treatment that could expose them to excessive risk. In some embodiments, subjects with GD do not have moderate to severe active thyroid ophthalmopathy (TED) and are not expected to require immediate surgical intervention and / or are planned to undergo corrective surgery / irradiation or medical therapy for TED during treatment. In some embodiments, subjects with GD do not have a history of non-compliance with ATD therapy.

[0234] Subjects with Graves' disease (GD) may suffer a rare but fatal medical event known as thyroid storm. A sudden and rapid rise in thyroid hormones can induce fever, sweating, delirium, severe weakness, tremors, irregular heartbeat, and severe hypotension and coma. In some implementations, the anti-FcRn therapies described herein (e.g., batolizumab or IMVT-1402) prevent or improve GD flares and / or thyroid storm.

[0235] In some implementations, baseline levels of thyroid function (e.g., T3, T4, TSH, and / or TRAb) in the subject may be assessed and recorded before initiation of anti-FcRn antibody (e.g., IMVT-1402 or battolimab). The levels of these parameters can be measured throughout treatment to assess efficacy. T3, T4, TSH, and / or TRAb can be measured using any suitable method.

[0236] In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) described herein reduces the subject's TSI level (e.g., relative to baseline TSI level before administration) by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the subject's TSI level (e.g., relative to baseline TSI level before administration) by 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 20% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 100%, 5% to 30%, 5% to 20%, 5% to 20%, 5% to 15%, 10% to 20%, 5% to 100%, 5% to 90%, 20% to 80%, 20% to 10% to 100%, 20% to 90%, 20% to 80%, 20% to 10% to 100%, 20% to 90%, 20% to 80%, 70%, 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.

[0237] In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) described herein reduces the subject's total IgG level (e.g., relative to baseline total IgG level before administration) by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the subject's total IgG level (e.g., relative to baseline total IgG level before administration) by 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, and 20%. Up to 70%, 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.

[0238] In some embodiments, subjects receiving the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) dosing regimen described herein achieve a state of normal thyroid function (e.g., become thyroid-normal) within 25 weeks of administration (e.g., within 25 weeks, 24 weeks, 23 weeks, 22 weeks, 21 weeks, 20 weeks, 19 weeks, 18 weeks, 17 weeks, 16 weeks, 15 weeks, 14 weeks, 13 weeks, 12 weeks, 11 weeks, 10 weeks, 9 weeks, 8 weeks, 7 weeks, 6 weeks, 5 weeks, 4 weeks, 3 weeks, 2 weeks, or 1 week). As used herein, normal thyroid function means having normal thyroid function. In some embodiments, subjects with normal thyroid function have T3 (total T3 or FT3), FT4, and TSH levels within the normal range. In some implementations, subjects are maintained in a normal thyroid state by continuing administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) dosing regimen described herein, relative to subjects who discontinue treatment at 26 weeks.

[0239] In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) described herein reduces the subject's T3 level (e.g., relative to baseline T3 level before administration) by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the subject's T3 level (e.g., relative to baseline T3 level before administration) by 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 70%, etc. 0%, 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%. In some embodiments, administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) dosing regimen described herein reduces the subject's T3 level to the normal range of T3 (e.g., 79 to 165 ng / dL).

[0240] In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) dosing regimen described herein reduces the subject's FT4 level (e.g., relative to baseline FT4 level before administration) by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the subject's FT4 level (e.g., relative to baseline FT4 level before administration) by 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 20% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 100%, 5% to 30%, 5% to 20%, 5% to 20%, 5% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 1 ... 70%, 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%. In some embodiments, administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) dosing regimen described herein reduces the subject's FT4 level to the normal range for FT4 (e.g., 0.7 to 1.9 ng / dL).

[0241] In some embodiments, administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) described herein results in an increase in the subject's TSH level (e.g., relative to baseline TSH level prior to administration) of at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 100%, at least 1.5 times, at least 2 times, at least 3 times, at least 4 times, at least 5 times, at least 10 times, at least 20 times, at least 50 times, at least 100 times or more.In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein results in an increase in the subject's TSH level (e.g., relative to baseline TSH level before administration) of 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, and 10% to 40%. 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 70%, 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 90%, 50% to 10 ... 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, 90% to 100%, 1 to 100 times, 1 to 90 times, 1 to 80 times, 1 to 70 times, 1 to 60 times, 1 to 50 times, 1 to 40 times, 1 to 30 times, 1 to 20 times, 1 to 10 times, 1 to 8 times, 1 to 5 times, 1 to 3 times, 5 to 100 times, 5 to 90 times, 5 to 80 times, 5 to 70 times, 5 to 60 times, 5 to 50 times, 5 to 40 times, 5 to 30 times, 5 to 20 times, 5 to 10 times, 5 to 8 times, 10 to 100 times, 10 to 90 times, 10 to 80 times, 10 to 70 times, 10 to 60 times, 10 to 50 times, 10 to 40 times, 10 to 30 times, 10 to 20 times, 25 to 100 times, 25 to 90 times, 25 to 80 times, 25 to 70 times, 25 to 60 times, 25 to 50 times, 25 to 40 times, 25 to 30 times, 50 to 100 times, 50 to 90 times, 50 to 80 times, 50 to 70 times, 50 to 60 times, 75 to 100 times, 75 to 90 times, and 75 to 80 times. In some embodiments, administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) as described herein increases the subject's TSH level to the normal range (e.g., 0.5 to 5.0 mU / L).

[0242] In some embodiments, the dose of the ATD received by the subject may be adjusted during treatment based on T3, T4, and / or TSH levels and / or the subject's clinical response. For example, in some embodiments, administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimen described herein reduces the subject's T3 and / or T4 levels to below the ULN, thus the subject receives a reduced dose of the ATD. In some embodiments, subjects administering the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimen described herein may reduce the dose of the ATD within 60 weeks, 55 weeks, 50 weeks, 45 weeks, 40 weeks, 35 weeks, 30 weeks, 25 weeks, 20 weeks, 15 weeks, 10 weeks, or 5 weeks of administration. In some embodiments, administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimen described herein induces normal thyroid function in the subject, and the subject may discontinue the ATD. In some embodiments, subjects receiving the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) dosing regimen described herein discontinue ATD within 60, 55, 50, 45, 40, 35, 30, 25, 20, 15, 10, or 5 weeks of administration.

[0243] In some embodiments, the subject may gradually reduce the dose of the anti-FcRn antibody (e.g., 680 mg of battolimab or 600 mg of IMVT-1402) to eventually discontinue the ATD. In some embodiments, the subject may then begin receiving a lower dose of the anti-FcRn antibody (e.g., 340 mg of battolimab or 300 mg of IMVT-1402), but the dose may need to be increased or the ATD reintroduced to maintain normal T3 and / or T4 levels. In other embodiments, the subject continues to receive a high dose of the anti-FcRn antibody (e.g., 680 mg of battolimab or 600 mg of IMVT-1402) while continuing to receive a low dose of the ATD or discontinuing the ATD and maintaining normal T3 and / or T4 levels. Therefore, in some embodiments, this disclosure provides a method for treating Graves' disease (GD) in a subject receiving an antithyroid drug (ATD) at a dose, the method comprising: (i) administering an anti-FcRn antibody (e.g., 680 mg of battolimab or 600 mg of IMVT-1402) to the subject at a dose in the range of 580 to 700 mg; (ii) measuring the subject's T3 and T4 levels; (iii) if the T3 and / or T4 levels are below the ULN, reducing the dose of the ATD or discontinuing the ATD; (iii) reducing the dose of the anti-FcRn antibody to a dose in the range of 280 to 400 mg / dose (e.g., 340 mg of battolimab or 300 mg of IMVT-1402); and (iv) increasing the dose of the subject's ATD or restarting the subject's ATD to maintain T3 and T4 levels below the ULN. In some embodiments, this disclosure provides a method for treating Graves' disease (GD) in a subject receiving an antithyroid drug (ATD) at a dose, the method comprising: (i) administering an anti-FcRn antibody (e.g., 680 mg of battolimab or 600 mg of IMVT-1402) to the subject at a dose in the range of 580 to 700 mg; (ii) measuring the subject's T3 and T4 levels; (iii) if the T3 and / or T4 levels are below the ULN, reducing the dose of the ATD or discontinuing the ATD; and (iii) maintaining the dose of the anti-FcRn antibody (e.g., 680 mg of battolimab or 600 mg of IMVT-1402) while administering a low dose of the ATD or not administering the ATD to the subject to maintain T3 and T4 levels below the ULN.

[0244] In some implementations, administering anti-FcRn antibodies (such as IMVT-1402 or battolimab) to subjects with GD improves their quality of life (QOL) scores. QOL scores include a self-assessment questionnaire that measures multiple aspects related to quality of life, such as anxiety, cognitive problems, overall QOL, appearance discomfort, depression (depressive disorder), mood susceptibility, eye symptoms, goiter symptoms, hyperthyroidism symptoms, hypothyroidism symptoms, impairment of daily living, overall QOL, social impairment, and fatigue. Item response scores for QOL assessment are: 0 = "None at all"; 1 = "Somewhat"; 2 = "Somewhat"; 3 = "Quite a lot"; and 4 = "Very / Completely". An exemplary questionnaire for assessing the QOL of subjects with GD is the Thyroid-Related Patient-Reported Outcome (ThyPRO) 39 scale (see, for example, Watt et al., Development of a short version of the Thyroid-Related Patient-Reported Outcome ThyPRO. Thyroid, 2015. 25(10): 1069-1079.).

[0245] In some embodiments, administration of anti-FcRn antibodies to subjects with GD prior to administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) improved their anxiety scores within 12 and / or 24 weeks. In some embodiments, administration of anti-FcRn antibodies to subjects with GD prior to administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) improved their cognitive problem scores within 12 and / or 24 weeks. In some embodiments, administration of anti-FcRn antibodies to subjects with GD prior to administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) improved their overall QOL scores within 12 and / or 24 weeks. In some embodiments, administration of anti-FcRn antibodies to a subject with GD prior to administration of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) improves the subject's appearance discomfort score within 12 weeks and / or 24 weeks. In some embodiments, administration of anti-FcRn antibodies to a subject with GD prior to administration of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) improves the subject's depression score within 12 weeks and / or 24 weeks. In some embodiments, administration of anti-FcRn antibodies to a subject with GD prior to administration of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) improves the subject's mood susceptibility score within 12 weeks and / or 24 weeks. In some embodiments, administration of anti-FcRn antibodies to subjects with GD prior to administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) improved ocular symptom scores within 12 and / or 24 weeks. In some embodiments, administration of anti-FcRn antibodies to subjects with GD prior to administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) improved goiter symptom scores within 12 and / or 24 weeks.

[0246] In some embodiments, administration of anti-FcRn antibodies improves hyperthyroidism symptom scores in subjects with pre-existing GD (GD) within 12 and / or 24 weeks compared to their hyperthyroidism symptom scores prior to administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab). In some embodiments, administration of anti-FcRn antibodies improves hypothyroidism scores in subjects with GD within 12 and / or 24 weeks compared to their hypothyroidism scores prior to administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab). In some embodiments, administration of anti-FcRn antibodies improves anxiety scores in subjects with GD within 12 and / or 24 weeks compared to their anxiety scores prior to administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab). In some embodiments, administration of anti-FcRn antibodies improves the daily living impairment score of subjects with GD prior to administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) within 12 and / or 24 weeks. In some embodiments, administration of anti-FcRn antibodies improves the overall QOL score of subjects with GD prior to administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) within 12 and / or 24 weeks. In some embodiments, administration of anti-FcRn antibodies improves the social impairment score of subjects with GD prior to administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) within 12 and / or 24 weeks. In some implementations, administration of anti-FcRn antibodies to a subject who had GD prior to administration of anti-FcRn antibodies (such as IMVT-1402 or battolimab) improved the subject's fatigue score within 12 weeks and / or 24 weeks.

[0247] In some implementations, administration of anti-FcRn antibodies to subjects with GD improved their anxiety scores, cognitive problems scores, overall QOL scores, appearance discomfort scores, depression scores, mood susceptibility scores, ocular symptoms scores, goiter symptoms scores, hyperthyroidism symptoms scores, hypothyroidism symptoms scores, impairment in daily living scores, overall QOL scores, social impairment scores, and / or fatigue scores within 12 and / or 24 weeks, compared to the corresponding scores before administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab).

[0248] In some embodiments, subjects exhibiting the improved QQL scores described herein are thyroid-normal and no longer receive ATDs after or during administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab). In other embodiments, subjects exhibiting the improved QQL scores described herein are thyroid-normal and continue to receive ATDs after or during administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab).

[0249] Dosage regimen for rheumatoid arthritis (RA)

[0250] Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation of the joints. In some cases, RA can cause inflammation of the lungs, eyes, mouth, and skin. The global prevalence of RA is estimated to be 0.5% to 1.0% of the population. Symptoms of RA include joint pain, stiffness, and swelling of both large and small joints. The pathophysiology of RA involves chronic inflammation of the synovium, which can destroy articular cartilage and proximal joint bone. If left untreated or poorly treated, RA can lead to joint destruction, severe disability, poor quality of life, and premature death.

[0251] Autoantibodies are detected in approximately 70% to 80% of RA patients, including rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA). RF is defined as an autoantibody against the Fc portion of IgG, and despite its name, it is not unique to RA and can be found in other disease symptoms. RF is found in multiple Ig isotypes (IgM, IgG, and IgA), and all three isotypes are present in more than half of RA patients, but only in less than 5% of healthy individuals.

[0252] Serological RA is associated with severe disease and adverse outcomes, including increased mortality. Serological positivity for RF and ACPA amplifies the disease and leads to an aggressive phenotype, including severe extra-articular manifestations. Furthermore, serological positivity for RF and ACPA, along with high disease activity at baseline and lung involvement, is associated with difficult-to-treat (D2T) RA. High-affinity and high-titer IgG RF in RA synovial fluid is believed to enhance inflammation and antigen capture in the joint by forming IgG-IC complexes, activating complement, and inducing leukocyte (immune cell) infiltration. Therefore, treatment of RA patients, especially those seropositive for RA, with the anti-FcRn therapy described herein (e.g., batolizumab or IMVT-1402) can improve or prevent symptom progression by shortening the half-life of destructive autoantibodies in the patient's system.

[0253] Criteria for determining whether an individual has rheumatoid arthritis (RA) have been established according to the American College of Rheumatology (ACR) / European League Against Rheumatism Collaborative Initiative (EULAR) (Aletaha et al., Rheumatoid arthritis classification criteria: an American College of Rheumatology / European League Against Rheumatism collaborative initiative. Arthritis Rheum, 2010. 62(9):2569-2581). The criteria for identifying RA are based on: the presence of synovitis in at least one joint, the absence of an alternative diagnosis to explain the synovitis, and an overall score ≥6 across four domains, including the number and location of affected joints (0 to 5), serological abnormalities (0 to 3), elevated acute response (0 to 1), and duration of symptoms (two levels, score range 0 to 1).

[0254] In some embodiments, an anti-FcRn therapy (e.g., battolimab or IMVT-1402) is administered to a subject suffering from RA to treat or improve their symptoms. In some embodiments, this disclosure provides compositions (e.g., IMVT-1402 or battolimab) and methods (e.g., dosing regimens) for treating a subject with RA.

[0255] In some implementations, subjects with RA are given an anti-FcRn antibody (e.g., IMVT-1402 or bartolimab) in the range of 550 to 700 mg once a week.

[0256] In some implementations, subjects with RA are administered anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) in the following ranges once weekly: 550 to 700 mg, 550 to 690 mg, 550 to 680 mg, 550 to 670 mg, 550 to 660 mg, 550 to 650 mg, 550 to 640 mg, 550 to 630 mg, 550 to 620 mg, 550 to 610 mg, 550 to 600 mg, 550 to 590 mg, 550 to 580 mg, 550 to 570 mg, 550 to 560 mg, 580 to 700 mg, 580 to 690 mg, 580 to 680 mg, 580 to 670 mg, 580 to 660 mg, 580 to 650 mg, 580 to 640 mg, 580 to 630 mg. mg, 580 to 620 mg, 580 to 610 mg, 580 to 600 mg, 580 to 590 mg, 600 to 700 mg, 600 to 690 mg, 600 to 680 mg, 600 to 670 mg, 600 to 660 mg, 600 to 650 mg, 600 to 640 mg, 600 to 630 mg, 600 to 620 mg, 600 to 610 mg, 620 to 700 mg, 620 to 690 mg, 620 to 680 mg, 620 to 670 mg, 620 to 660 mg, 620 to 650 mg, 620 to 640 mg, 620 to 630 mg, 650 to 700 mg, 650 to 690 mg, 650 to 680 mg, 650 to 670 mg, 650 to 660 mg mg, 680 to 700 mg or 680 to 690 mg.

[0257] In some embodiments, subjects are administered an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) in the range of 550 to 700 mg once weekly for at least 16 weeks (e.g., at least 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 weeks or longer). In some embodiments, subjects with RA are administered an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) in the range of 550 to 700 mg once weekly indefinitely. In some embodiments, a subject with RA is given 300 mg or 340 mg of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) once weekly indefinitely. In some embodiments, a subject with RA is given 600 mg or 680 mg of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) once weekly indefinitely. In some embodiments, a subject with RA is given 300 mg of IMVT-1402 once weekly indefinitely. In some embodiments, a subject with RA is given 600 mg of IMVT-1402 once weekly indefinitely. In some embodiments, a subject with RA is given 340 mg of battolimab once weekly indefinitely. In some embodiments, a subject with RA is given 680 mg of battolimab once weekly indefinitely.

[0258] In some embodiments, IMVT-1402 is administered to subjects with RA. In some embodiments, 600 mg of IMVT-1402 is administered to subjects with RA once weekly for 16 weeks. In some embodiments, after the initial 16 weeks of administration, subjects continue to receive 600 mg of IMVT-1402 once weekly. In some embodiments, after the initial 16 weeks of administration, subjects are subsequently administered 300 mg of IMVT-1402 once weekly.

[0259] In some implementations, the subject with RA has active RA. In some implementations, the subject with RA has refractory RA. Subjects with refractory RA are those who, despite having access to advanced therapies and having been exposed to multiple disease-modifying antirheumatic drugs (DMARDs), have not benefited from such treatment. Such subjects are differently designated as having "drug-resistant (D2T) RA," "treatment-resistant RA," or "refractory RA." In some implementations, refractory RA is defined by the following criteria: (i) failure of ≥2 b / tsDMARDs (with different mechanisms of action) after one treatment according to EULAR recommendations and failure of csDMARD therapy (unless contraindicated); (ii) signs suggesting active / progressive disease, defined as at least one of the following: a. at least moderate disease activity (based on validated comprehensive measurements, including joint counts, e.g., DAS28-ESR > 3.2 or CDAI > 10); b. signs (including acute-phase reactants and imaging) and / or symptoms suggesting active disease (joint-related or otherwise); c. inability to gradually reduce glucocorticoid therapy (below 7.5). (d) Prednisone or equivalent (mg / day); (e) Rapid radiographic progression (with or without signs of active disease) indicated by a change of ≥5 points in the Van der Heyd modified Sharp score over 1 year; (iii) Good disease control according to the above criteria, but still with RA symptoms that reduce quality of life; (iv) Rheumatologists and / or subjects believe that there are problems with the management of signs and / or symptoms.

[0260] In some embodiments, subjects with RA are positive for RF. In some embodiments, the synovial fluid of subjects with RA is positive for IgG or IgA RF. In some embodiments, the baseline RF level of subjects is higher than 25 U / ml, higher than 30 U / ml, higher than 35 U / ml, higher than 40 U / ml, higher than 45 U / ml, higher than 50 U / ml, higher than 55 U / ml, higher than 60 U / ml, higher than 65 U / ml, higher than 70 U / ml, higher than 75 U / ml, higher than 80 U / ml, higher than 85 U / ml, higher than 90 U / ml, higher than 95 U / ml, higher than 100 U / ml, higher than 120 U / ml, higher than 150 U / ml, higher than 180 U / ml, higher than 200 U / ml, higher than 250 U / ml, higher than 300 U / ml, higher than 350 U / ml, higher than 400 U / ml, higher than 450 U / ml, higher than 500 U / ml, or higher.In some implementations, the baseline RF level of the object is in the following ranges: 25 to 500 U / ml, 25 to 450 U / ml, 25 to 400 U / ml, 25 to 350 U / ml, 25 to 300 U / ml, 25 to 250 U / ml, 25 to 200 U / ml, 25 to 150 U / ml, 25 to 100 U / ml, 25 to 75 U / ml, 25 to 50 U / ml, 50 to 500 U / ml, 50 to 450 U / ml, 50 to 400 U / ml, 50 to 350 U / ml, 50 to 300 U / ml, 50 to 250 U / ml, 50 to 200 U / ml, 50 to 150 U / ml, 50 to 100 U / ml, 50 to 75 U / ml, 100 to 500 U / ml, 100 to 450 U / ml. U / ml, 100 to 400 U / ml, 100 to 350 U / ml, 100 to 300 U / ml, 100 to 250 U / ml, 100 to 200 U / ml, 100 to 150 U / ml, 150 to 500 U / ml, 150 to 450 U / ml, 150 to 350 U / ml, 150 to 250 U / ml, 150 to 200 U / ml, 200 to 500 U / ml, 200 to 450 U / ml, 200 to 400 U / ml, 200 to 350 U / ml, 200 to 300 U / ml, 200 to 250 U / ml, 250 to 500 U / ml, 250 to 450 U / ml, 250 to 400 U / ml U / ml, 250 to 350 U / ml, 250 to 300 U / ml, 300 to 500 U / ml, 300 to 450 U / ml, 300 to 400 U / ml, 300 to 350 U / ml, 400 to 500 U / ml, 400 to 450 U / ml or 450 to 500 U / ml.

[0261] In some implementations, subjects with RA have at least 6 / 68 (e.g., at least 7 / 68, at least 10 / 68, at least 15 / 68, at least 20 / 68, at least 25 / 68, at least 30 / 68, at least 35 / 68, at least 40 / 68, at least 45 / 68, at least 50 / 68, at least 55 / 68, at least 60 / 68, at least 65 / 68, or 68 / 68) tender / painful joints (TJCs) at baseline.

[0262] In some implementations, subjects with RA have at least 6 / 66 (e.g., at least 6 / 66, at least 7 / 66, at least 10 / 66, at least 15 / 66, at least 20 / 66, at least 25 / 66, at least 30 / 66, at least 35 / 66, at least 40 / 66, at least 45 / 66, at least 50 / 66, at least 55 / 66, at least 60 / 66, at least 65 / 66, or 66 / 66) swollen joints (SJCs) at baseline.

[0263] In some implementations, subjects with RA have a baseline disease activity score28 (DAS28-CRP>4.1) as determined using C-reactive protein.

[0264] In some embodiments, subjects with RA have an inadequate response to 2 to 3 classes of biological and targeted synthetic DMARDs (b / tsDMARDs). In some embodiments, subjects with RA have been treated with biological TNFα inhibitors (e.g., infliximab, cetrus, golimumab, etanercept, or adalimumab) and have been intolerant or experienced inadequate efficacy (including loss of efficacy) at a given dose and duration. In some embodiments, subjects have been treated with JAK inhibitors or at least one additional bDMARD other than a TNFα inhibitor and have experienced inadequate efficacy (including loss of efficacy) at a given dose and duration. In some embodiments, subjects have not responded adequately to rituximab. In some embodiments, subjects with RA have been regularly treated with at least one cDMARD (e.g., MTX, hydroxychloroquine, and / or sulfasalazine) for ≥12 weeks at baseline. In some implementations, subjects starting the anti-FcRn therapy described herein (e.g., batolizumab or IMVT-1402) receive MTX at a stable, constant oral dose of 15 to 25 mg / week (e.g., at least 8 weeks prior to administration).

[0265] In some embodiments, the subject with RA has not received more than three DMARDs prior to administration. In some embodiments, the subject with RA is not receiving glucocorticoids at doses >10 mg / day. In some embodiments, the subject with RA has not received intra-articular glucocorticoids in three or more joints. In some embodiments, the subject with RA has not received any parenteral glucocorticoids administered via intramuscular (IM) or intravenous (IV) injection. In some embodiments, the subject with RA is not expected to require parenteral glucocorticoids while receiving the anti-FcRn therapy described herein (e.g., batolizumab or IMVT-1402). In some embodiments, the subject with RA has not received rituximab and has experienced inadequate efficacy (including loss of efficacy). In some embodiments, the subject with RA has not responded inadequately to more than three b / tsDMARDs with different mechanisms of action as RA therapeutic agents. In some embodiments, subjects with RA have not started NSAID treatment within 2 weeks prior to initiating the anti-FcRn therapy described herein (e.g., batolizumab or IMVT-1402) or within 6 weeks prior to baseline assessment, where the NSAID is intended to treat signs and symptoms of RA. In some embodiments, subjects with RA do not have Felty's syndrome.

[0266] In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the subject's RF level (e.g., relative to baseline RF level before administration) by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. The dosing regimens of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein resulted in a reduction of RF levels (e.g., relative to baseline RF levels before administration) of 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 70%, and 20% to 20% to 100%, 20% to 90%, 20% to 80%, and 20% to 70%, respectively. % to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.

[0267] In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) described herein reduces the subject's ACAP level (e.g., relative to baseline ACAP level before administration) by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. The dosing regimens of the anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) described herein resulted in a reduction of ACAP levels (e.g., relative to baseline ACAP levels before administration) of 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, and 20% to 70%. 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.

[0268] In some embodiments, subjects receiving the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimen described herein achieved an ACR20 response at week 14, week 16, or week 32 of administration. In some embodiments, the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimen described herein resulted in an improvement in TJC68 relative to baseline TJC68 of at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) described herein results in an improvement of SJC66 by at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% relative to baseline SJC66.

[0269] In some embodiments, administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) dosing regimen described herein results in at least 20% improvement (e.g., at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) of at least three of the following parameters relative to their respective baseline levels: (i) Physician Global Disease Activity Assessment (PhGA); (ii) Patient Global Disease Activity Assessment (PtGA); (iii) Patient Pain Assessment (100 mm VAS); (iv) Health Assessment Questionnaire-Disability Index (HAQ-DI); and (v) High Sensitivity C-Reactive Protein (hsCRP).

[0270] In some embodiments, subjects with RA who received the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimen described herein showed changes in achieving an ACR20 response from week 14 to week 16 of administration and changes in their CDAI score from week 16 to week 32 of administration. In some embodiments, subjects with RA who received the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimen described herein showed changes in achieving an ACR20 response from week 14 to week 16 of administration and changes in their SDAI score from week 16 to week 32 of administration.

[0271] Individuals with rheumatoid arthritis (RA) may occasionally experience RA flares, in which symptoms worsen or new symptoms appear. RA flares can involve any exacerbation of symptoms, but most commonly involve severe pain and stiffness in the joints. In addition to worsening joint-related symptoms, RA flares may cause fatigue, weight loss, fever, general aches and pains, inflammatory nodules under the skin, rash, dry eye, and / or flu-like symptoms. Less common symptoms of RA flares may include hearing problems such as tinnitus, difficulty breathing, numbness and tingling, sleep disturbances, and gastrointestinal problems. RA flares typically last about 3 days, but may last longer or subside earlier. In some implementations, the anti-FcRn therapies described herein (such as batolizumab or IMVT-1402) prevent or improve RA flares.

[0272] Dosage regimen for myasthenia gravis (MG)

[0273] In some aspects, this disclosure provides compositions and methods for treating myasthenia gravis (MG). In some embodiments, the method includes a dosing regimen for MG (e.g., dosage, dosing frequency, etc.) that improves the therapeutic efficacy of MG (e.g., relative to using a different dosing regimen).

[0274] Myasthenia gravis (MG) is a rare, potentially fatal chronic autoimmune neuromuscular disease caused by autoantibodies against the postsynaptic muscle membrane at the neuromuscular junction, leading to muscle weakness and fatigue. There are two peak incidence periods: early-onset MG occurs in people aged 20 to 30 (primarily women) and late-onset MG occurs in the elderly (primarily men). The prevalence of MG varies geographically, ranging from 2.19 to 36.71 cases per 100,000 people.

[0275] Most patients with myasthenia gravis (MG) have unilateral or bilateral involvement of the muscles that control eye and eyelid movement, as these muscles are particularly prone to weakness (i.e., ocular myasthenia gravis, oMG). Typical symptoms of oMG include intermittent ptosis (drooping eyelid) and diplopia (diplopia). In approximately 80% of patients, oMG precedes the more severe generalized myasthenia gravis (gMG), in which the bulbar muscles, axial muscles, limb muscles, and / or respiratory muscles controlling chewing, speaking, and swallowing are frequently affected. If a patient has had a localized ocular condition for 2 years without developing gMG, they are unlikely to develop gMG later.

[0276] The diagnosis of myofascitis (MG) is confirmed by a combination of relevant signs and symptoms and a positive specific autoantibody test. Autoantibody specificity and clinical presentation characterize different subgroups of MG. Approximately 80% of MG patients have detectable immunoglobulin G1 (IgG1) and immunoglobulin G3 (IgG3) subclass antibodies (“anti-AChR+”) against acetylcholine receptors (AChR) expressed on the muscle membrane. Autoantibodies binding to AChR can have various effects, including activating the complement cascade, which leads to the formation of the membrane attack complex and damage to the postsynaptic membrane.

[0277] Muscle-specific kinase (MuSK), along with lipoprotein receptor-associated protein 4 (LRP4), is responsible for the maintenance of AChR clustering and neuromuscular junctions. Autoantibodies against MuSK are detected in approximately 1% to 10% of patients, and these are immunoglobulin G4 (IgG4) subclass autoantibodies (“anti-MuSK+”). Therefore, they do not activate the complement cascade but exert their pathogenicity by blocking the interaction between MuSK and LRP4, which is required for AChR clustering. In patients with anti-MuSK+ MG, anti-MuSK concentrations often correlate with disease severity, and changes in antibody concentration over time can reflect disease activity.

[0278] Antibodies against LRP4 (“anti-LRP4+”) are detected in 1% to 5% of patients with any type of MG and in 7% to 33% of patients who do not have AChR and MuSK antibodies. Autoantibodies against LRP4 are IgG1 subclasses, and their primary pathogenic mechanism is through activation of the complement cascade. Patients who do not have detectable antibodies against any of these three antigens are called seronegative (10% to 15% of MG patients). Diagnosis of MG in seronegative patients is based on thorough clinical examination and neurophysiological testing.

[0279] The primary goal of treatment is to improve functional abilities and quality of life by minimizing the severity of MG symptoms to a minimum, while avoiding significant drug-induced adverse effects. Treatment should be tailored to the individual patient's MG subgroup. Cholinesterase inhibitors, such as pyridostigmine, prevent the degradation of acetylcholine and thus increase its availability at the neuromuscular junction, which improves neuromuscular transmission and symptoms, especially in anti-AChR+ patients. Immunosuppressive therapy can induce improvement in patients who do not respond adequately to symptom therapy. Glucocorticoids are first-line immunosuppressants; however, nonsteroidal immunosuppressants (e.g., azathioprine, cyclosporine, mycophenolate mofetil, methotrexate, rituximab, and tacrolimus) can be used. Plasma exchange (PLEX) and intravenous immunoglobulin (IVIg) are rapidly acting treatments and are often used in patients with acute, severe MG, where a rapid response is crucial. Because its effects are short-lived (4 to 12 weeks), additional immunotherapy is usually required.

[0280] The treatment paradigm for managing myoglobulin muscular sclerosis (MG) continues to evolve with the introduction of new therapies. For anti-AChR+ patients, complement inhibitors that prevent the formation of the membrane attack complex (eculizumab, ravulizumab, and zilucoplan) have demonstrated clinical efficacy and have been approved by the US Food and Drug Administration (FDA). Based on data from IVIg, rituximab, and neonatal crystallizable fragment receptor (FcRn) blockers, reducing the level of pathogenic immunoglobulin G (IgG) autoantibodies in gMG is associated with clinical benefit. For the FcRn blockers efgartigimod and rozanolixizumab, the reduction in pathogenic autoantibodies ranges from 40% to 70%, depending on the study and duration of treatment, and both are FDA-approved for the treatment of gMG. Other FcRn blockers are in clinical development; for example, nipocalimab and battolimab. The emergence of new therapies may revolutionize the treatment of MG.

[0281] Current immunomodulatory therapies have improved the prognosis of patients with myocardial infarction (MG). However, high doses of corticosteroids are often required to achieve improvement or remission, and long-term treatment with corticosteroids and other immunosuppressive therapies is usually necessary. Complement inhibitors carry a significant risk of meningococcal meningitis and require vaccination and careful monitoring before initiating therapy. Furthermore, patients not included in the approved indications (anti-AChR+ or anti-MuSK+), such as 10% to 15% of seronegative MG patients, are ineligible for this treatment.

[0282] For patients with gMG, quality of life is widely and significantly negatively impacted, including daily activities such as eating, walking, and speaking. Overall, persistent muscle weakness associated with gMG typically negatively interferes with patients' ability to participate in daily activities, including work, family, social functioning, and physical activity needs.

[0283] Despite the availability of chronic immunosuppressive therapy, patients with gMG may experience acute exacerbations. Within the first two years after MG diagnosis, approximately 15% to 20% of MG patients experience life-threatening myasthenic crisis requiring mechanical ventilation and long-term intensive care. The mean annualized hospitalization rate for acute exacerbations is 4.4%, while the mean annualized hospitalization rate for myasthenic crisis is 6.8%. The mean length of hospital stay for acute exacerbations ranges from 11.3 to 13.1 days, but the mean length of hospital stay for crisis admissions can be significantly longer. Even with established intensive care protocols, myasthenic crisis is associated with a 5% to 12% in-hospital mortality rate. The most common causes of death are multi-organ failure and respiratory failure due to sepsis. Therefore, there remains an unmet need for more effective treatments that can be administered chronically and safely, providing faster benefits and preventing the risk of rapid physical decline.

[0284] Therefore, treating subjects with MG, especially those who are MG seropositive, with the anti-FcRn therapies described in this article (such as batolizumab or IMVT-1402) can improve or prevent symptom progression by shortening the half-life of destructive autoantibodies in the subject's system.

[0285] The criteria for determining whether a subject has MG and the severity of MG have been established according to the Myasthenia Gravis Foundation of America (MGFA). MG severity is divided into grades I to V (Jaretzki et al., Myasthenia gravis: recommendations for clinical research standards. Nurology, 2000. 55(1): 16-23). ​​The grades of MG and the individual criteria are as follows:

[0286] Grade I: Weakness of any ocular muscle; may have difficulty closing the eyes. All other muscle strength is normal.

[0287] Grade II: Mild weakness affecting muscles other than the eye muscles; may also include any degree of eye muscle weakness.

[0288] IIa. Primarily affects limb muscles, axial muscles, or both. May also involve fewer oropharyngeal muscles.

[0289] IIb. Primarily affects the oropharyngeal muscles, respiratory muscles, or both. May also involve fewer or equal numbers of limb muscles, axial muscles, or both.

[0290] Grade III: Moderate weakness affecting muscles other than the eye muscles; may also include any degree of eye muscle weakness.

[0291] IIIa. Primarily affects limb muscles, axial muscles, or both. May also involve fewer oropharyngeal muscles.

[0292] IIIb. Primarily affects the oropharyngeal muscles, respiratory muscles, or both. May also involve fewer or equal numbers of limb muscles, axial muscles, or both.

[0293] Grade IV: Severe weakness affecting muscles other than the eye muscles; may also include any degree of eye muscle weakness.

[0294] IVa. Primarily affects limb muscles, axial muscles, or both. May also involve fewer oropharyngeal muscles.

[0295] IVb. Primarily affects the oropharyngeal muscles, respiratory muscles, or both. May also involve fewer or equal numbers of limb muscles, axial muscles, or both.

[0296] Grade V: Defined as intubated, with or without mechanical ventilation, except when used during routine postoperative management. Using a feeding tube without intubation places the patient in Grade IVb.

[0297] In some embodiments, an anti-FcRn therapy (e.g., battolimab or IMVT-1402) is administered to a subject suffering from MG to treat or improve their symptoms. In some embodiments, this disclosure provides compositions (e.g., IMVT-1402 or battolimab) and methods (e.g., dosing regimens) for treating a subject with MG.

[0298] In some implementations, subjects with MG are given an anti-FcRn antibody (e.g., IMVT-1402 or bartolimab) in the range of 550 to 700 mg once a week.

[0299] In some implementations, subjects with MG are administered anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) in the following ranges once weekly: 550 to 700 mg, 550 to 690 mg, 550 to 680 mg, 550 to 670 mg, 550 to 660 mg, 550 to 650 mg, 550 to 640 mg, 550 to 630 mg, 550 to 620 mg, 550 to 610 mg, 550 to 600 mg, 550 to 590 mg, 550 to 580 mg, 550 to 570 mg, 550 to 560 mg, 580 to 700 mg, 580 to 690 mg, 580 to 680 mg, 580 to 670 mg, 580 to 660 mg, 580 to 650 mg, 580 to 640 mg, 580 to 630 mg. mg, 580 to 620 mg, 580 to 610 mg, 580 to 600 mg, 580 to 590 mg, 600 to 700 mg, 600 to 690 mg, 600 to 680 mg, 600 to 670 mg, 600 to 660 mg, 600 to 650 mg, 600 to 640 mg, 600 to 630 mg, 600 to 620 mg, 600 to 610 mg, 620 to 700 mg, 620 to 690 mg, 620 to 680 mg, 620 to 670 mg, 620 to 660 mg, 620 to 650 mg, 620 to 640 mg, 620 to 630 mg, 650 to 700 mg, 650 to 690 mg, 650 to 680 mg, 650 to 670 mg, 650 to 660 mg mg, 680 to 700 mg or 680 to 690 mg.

[0300] In some embodiments, subjects are administered an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) in the range of 550 to 700 mg once weekly for at least 12 weeks (e.g., at least 12, 13, 14, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 weeks or longer). In some embodiments, subjects with MG are administered an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) in the range of 550 to 700 mg once weekly indefinitely. In some embodiments, subjects are administered 600 mg or 680 mg of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) once weekly for 12 weeks. In some embodiments, subjects with myocardial infarction (MG) are administered 300 mg or 340 mg of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) once weekly indefinitely. In some embodiments, subjects with myocardial infarction (MG) are administered 600 mg of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) once weekly indefinitely. In some embodiments, subjects with myocardial infarction (MG) are administered 300 mg of IMVT-1402 once weekly indefinitely. In some embodiments, subjects with myocardial infarction (MG) are administered 600 mg of IMVT-1402 once weekly indefinitely. In some embodiments, subjects with myocardial infarction (MG) are administered 340 mg of battolimab once weekly indefinitely. In some implementations, subjects with MG are given 680 mg of batolizumab once a week indefinitely.

[0301] In some embodiments, IMVT-1402 is administered to subjects with myasthenia gravis (MG). In some embodiments, 600 mg of IMVT-1402 is administered to subjects with MG once weekly for 12 weeks. In some embodiments, after the initial 12 weeks of administration, subjects continue to receive 600 mg of IMVT-1402 once weekly. In some embodiments, after the initial 12 weeks of administration, subjects are subsequently administered 300 mg of IMVT-1402 once weekly.

[0302] In some embodiments, subjects with MG have mild to severe MG of grade I, II, III, or IV at the initial screening visit. In some embodiments, for subjects with grade I MG, the duration of the disease is no more than 2 years (e.g., the subject has not had grade I MG for more than 2 years). In some embodiments, subjects with MG have diagnostic autoantibody confirmation of MG at the initial screening visit, wherein the autoantibodies include anti-AChR autoantibodies, anti-MuSK autoantibodies, and / or anti-LRP4 autoantibodies. In some embodiments, subjects with MG who are seronegative for known antibodies have a history of abnormal neuromuscular conduction tests demonstrated by single-fiber electromyography or repetitive nerve stimulation and one of the following: (i) a history of a positive edrophonium chloride test; and / or (ii) an improvement in MG signs as assessed by a physician upon receiving oral cholinesterase inhibitors, IVIg, or PLEX. In some embodiments, subjects with MG have an MG-ADL score of ≥5 at the initial screening visit and baseline visit (e.g., day 1 of treatment with anti-FcRn antibodies). In some embodiments, subjects with MG have a quantitative myasthenia gravis (QMG) score of ≥11 at the initial screening visit and baseline visit (e.g., day 1 of treatment with anti-FcRn antibodies). In some embodiments, subjects with grade I MG do not have a QMG score of ≥11 at the initial screening visit and baseline visit (e.g., day 1 of treatment with anti-FcRn antibodies). In some embodiments, subjects with MG have been treated or are being treated with one or more of the following:

[0303] (a) Corticosteroids and / or cholinesterase inhibitors, subject to the following conditions:

[0304] (i) Corticosteroids: A stable weekly (QD) dose of ≤30 mg prednisone or equivalent for ≥6 weeks prior to the initial screening visit, during which the following dose regimens are permitted:

[0305] (1) For participants receiving <15 mg prednisone QD or equivalent, a daily dose shift of ≤2.5 mg or equivalent is permitted once; and

[0306] (2) For participants receiving ≥15 mg to ≤30 mg prednisone QD or equivalent, a daily dose offset of ≤5 mg or equivalent is permitted once;

[0307] (ii) Cholinesterase inhibitors: a stable dose (without change) for ≥4 weeks prior to the initial screening visit; and / or

[0308] (b) Nonsteroidal immunosuppressants: Use at most one of the following medications that meet the following criteria:

[0309] (i) Use of methotrexate, azathioprine, or mycophenolate mofetil for ≤6 months or ≥18 months prior to the initial screening visit, without dose adjustment for ≥3 months; and

[0310] (ii) Use of cyclosporine, cyclophosphamide or tacrolimus for ≥5 months prior to the initial screening visit, and no dose adjustment for ≥3 months.

[0311] In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the subject's anti-AChR autoantibody level (e.g., relative to baseline anti-AChR autoantibody level before administration) by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. Administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimens described herein resulted in a reduction of the subject's anti-AChR autoantibody levels (e.g., relative to baseline anti-AChR autoantibody levels before administration) by 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, and 20% respectively. Up to 70%, 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.

[0312] In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the subject's anti-MuSK autoantibody level (e.g., relative to baseline anti-MuSK autoantibody level before administration) by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. Administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimens described herein resulted in a reduction of the subject's anti-MuSK autoantibody levels (e.g., relative to baseline anti-MuSK autoantibody levels before administration) by 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, and 20% respectively. Up to 70%, 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.

[0313] In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the subject's anti-LRP4 autoantibody level (e.g., relative to baseline anti-LRP4 autoantibody level before administration) by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. Administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimens described herein resulted in a reduction of the subject's anti-LRP4 autoantibody levels (e.g., relative to baseline anti-LRP4 autoantibody levels before administration) by 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, and 20% respectively. Up to 70%, 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.

[0314] In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the subject's anti-AChR autoantibody levels, anti-MuSK autoantibody levels, and / or anti-LRP4 autoantibody levels (e.g., relative to baseline anti-AChR autoantibody levels, anti-MuSK autoantibody levels, and / or anti-LRP4 autoantibody levels before administration) by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. Administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimens described herein resulted in a reduction of the subject's anti-AChR autoantibody levels, anti-MuSK autoantibody levels, and / or anti-LRP4 autoantibody levels (e.g., relative to baseline anti-AChR autoantibody levels, anti-MuSK autoantibody levels, and / or anti-LRP4 autoantibody levels before administration) by 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 20%. 20% to 100%, 20% to 90%, 20% to 80%, 20% to 70%, 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 8 ...100%, 40% to 90%, 40% to 100%, 40% to 100%, 40% to 90%, 40% to 100%, 40% to 100%, 40% to 100%, 40% to 100%, 40% to 100%, 40% to 100%, 40% to 100%, 40% to 100%, % to 70%, 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.

[0315] In some implementations, subjects receiving the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) dosing regimens described herein showed changes in their QMG scores compared to their baseline QMG scores at weeks 10, 12, and / or 24 of administration.

[0316] In some embodiments, subjects receiving the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimen described herein show changes in their MG-ADL (Massage of Daily Living) scores compared to baseline at weeks 10, 12, and / or 24 of administration. MG-ADL scores include assessments related to speaking, chewing, swallowing, breathing, brushing or combing hair, rising from a sitting position, diplopia, and ptosis. In some embodiments, subjects receiving the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimen described herein show a change in their MG-ADL score of ≥2 points compared to baseline at weeks 10, 12, and / or 24 of administration. In some embodiments, subjects receiving the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimen described herein show an MG-ADL score of 0 or 1 up to week 10 or 12 of administration. In some implementations, subjects receiving the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) dosing regimens described herein showed changes in their QOL15r scores compared to baseline at weeks 10, 12, and / or 24 of administration. The Myasthenia Gravis QOL15r Scale is a 15-item quality of life scale designed to assess aspects of a subject's MG experience. The QOL15r scale assesses aspects of a subject's: depression; eye problems (e.g., diplopia); difficulty eating; limited social activity; enjoyment of hobbies or recreational activities; difficulty meeting the needs of family members; planning; limitations in performing work (including working from home); difficulty speaking; personal independence (e.g., driving, shopping, running errands); depression; difficulty walking; access to public places; disorientation; and difficulty meeting personal grooming needs, all related to a subject's MG.

[0317] In some embodiments, subjects receiving the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimen described herein showed changes in their Myasthenia Gravis Impairment Index (MGII) whole-body score at weeks 10, 12, and / or 24 of administration compared to their baseline visit. In some embodiments, subjects receiving the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) dosing regimen described herein showed changes in their serum total IgG and IgG subclasses 1-4 at weeks 10, 12, and / or 24 of administration compared to their baseline visit.

[0318] Subjects with myocardial infarction (MG) may occasionally experience MG flares, in which symptoms worsen or new symptoms appear. MG flares can involve an exacerbation of any symptom, but most commonly involve weakness or increased weakness in some or all muscles of the body. MG flares can also cause diplopia or worsening diplopia, slurred speech, increased arm weakness, falls, unsteady gait, dysphagia, chronic fatigue, or difficulty breathing. MG flares last one day, with symptoms fluctuating from one day to the next, but can also last for weeks or even months. In some implementations, the anti-FcRn therapies described herein (such as batolizumab or IMVT-1402) prevent or improve MG flares.

[0319] Dosage regimen for chronic inflammatory demyelinating polyneuropathy (CIDP)

[0320] In some aspects, this disclosure provides compositions and methods for treating chronic inflammatory demyelinating polyneuropathy (CIDP). In some embodiments, the method includes a CIDP administration regimen (e.g., dosage, administration frequency, etc.) that improves the therapeutic efficacy of CIDP (e.g., relative to using a different administration regimen).

[0321] Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated neuropathy affecting peripheral nerves and nerve roots. CIDP presents with symmetrical involvement of proximal and distal limb muscle weakness. In some embodiments, CIDP is triggered by stimuli such as molecular similarity that induce autoreactive T cell activation. Activated T cells cross the blood-nerve barrier (BNB) via adhesion molecules and hemocytosis, where they secrete metalloproteinases and pro-inflammatory cytokines. These substances increase BNB permeability and stimulate plasma cells to produce autoantibodies. Damaged BNB allows soluble factors such as antibodies and complement, as well as activated macrophages, to pass through, releasing pro-inflammatory cytokines and reactive oxygen species, thereby spreading the inflammatory cycle. In some cases, upon entering the nerve, autoantibodies can bind to neuronal proteins, including myelin glycoproteins, causing complement activation and macrophage-mediated axonal degeneration and demyelination. Autoantibody-induced degeneration and demyelination cause characteristic electrophysiological changes in peripheral nerves (e.g., prolonged remote latency and decreased motor conduction velocity). In some implementations, degeneration and demyelination clinically manifest as sensorimotor deficits in CIDP.

[0322] The diagnosis of CIDP is based on the fulfillment of clinical and electrodiagnostic criteria. Typical clinical criteria for CIDP in a subject include: (a) progressive or recurrent, symmetrical, proximal and distal muscle weakness in the upper and lower extremities, and sensory involvement in at least two extremities; and (b) a clinical course that has developed over at least 8 weeks; and (c) the absence or diminished tendon reflexes in all extremities. In some embodiments, the subject has a CIDP variant that presents with typical CIDP clinical criteria, but tendon reflexes in unaffected extremities may be normal, and one or more other symptoms may be present based on the specific variant. In some embodiments, the CIDP variant is distal CIDP, presenting with distal sensory loss and muscle weakness, primarily in the lower extremities. In some embodiments, the CIDP variant is multifocal CIDP, presenting with a multifocal pattern of sensory loss and muscle weakness, usually asymmetrical, predominantly in the upper extremities. In some embodiments, the CIDP variant is focal CIDP, presenting with sensory loss and muscle weakness in only one extremity. In some embodiments, the CIDP variant is motor CIDP, presenting with motor signs and symptoms without sensory involvement. In some implementations, CIDP variants are sensory CIDP, which present with sensory signs and symptoms without motor involvement. In addition to clinical criteria, electrodiagnostic testing (e.g., neural conduction studies of sensory and motor nerves) is required for diagnosis, and established criteria support a diagnosis of CIDP or probable CIDP. In cases where only a "probable" level diagnosis is achieved, additional diagnostic testing can provide supporting evidence to confirm the diagnosis, subject to at least two of the following criteria being met:

[0323] ○ Research on empirical therapy: Objective responses to impairment and loss of energy scales, such as:

[0324] ● Causes and treatment of inflammatory neuropathy (INCAT);

[0325] ●Inflammatory Rosch's Global Loss of Energy Scale (I-RODS); or

[0326] ●Medical Research Committee Overall Score (MRC-SS) for treatment with intravenous immunoglobulin (IVIg), corticosteroids, or plasma exchange (PLEX);

[0327] Diagnostic imaging: Ultrasound to identify enlarged cross-sectional area at least two sites in the proximal median nerve and / or brachial plexus; or magnetic resonance imaging (MRI) to identify enlarged size of one or more spinal nerve roots;

[0328] Cerebrospinal fluid (CSF): Shows albumin cell dissociation (i.e., elevated CSF protein levels and normal CSF white blood cell [WBC] levels);

[0329] Nerve biopsy: reveals features such as edema, demyelination, and / or onion bulb formation; biological specimens are usually taken from the sural nerve and are generally only performed when less invasive diagnostic methods fail to confirm the diagnosis.

[0330] Given the heterogeneity of clinical presentations of CIDP, its differential diagnosis includes a large number of potential alternative diagnoses (e.g., hereditary neuropathy), which warrant consideration and may prompt additional laboratory testing (e.g., for diabetic neuropathy, multiple myeloma, inflammatory myopathy, vitamin B12 deficiency). Additionally, in some cases, the presence of certain antibodies (anti-fasciculin 155 (i.e., anti-NF155 autoantibody), anti-contactin 1 (i.e., anti-CNTN1 autoantibody), anti-contactin-associated protein 1 (i.e., anti-CASPR1 autoantibody), anti-NF140 / NF186 (i.e., anti-NF140 / NF186 autoantibody)) can indicate a diagnosis of autoimmune nodopathy. These symptoms respond poorly to typical CIDP treatments and are considered independent entities outside the framework of the currently revised European Academy of Neurology / Peripheral Nerve Society (EAN / PNS) CIDP diagnostic criteria.

[0331] First-line treatment for CIDP includes one or more of IVIg, subcutaneous immunoglobulin (SCIg), corticosteroids, and PLEX. In some implementations, patients with CIDP are treated with one of the three first-line therapies. In some implementations, for patients who do not achieve objective improvement (e.g., objective improvement in impairment and disability) after 3 months of treatment, other first-line agents may be tried. In some implementations, alternative treatment options include rituximab, cyclophosphamide, or cyclosporine. In some implementations, once objective improvement is achieved, patients may switch to maintenance therapy to reduce the dose or frequency of treatment to the lowest effective level. For maintenance therapy, patients may switch from IVIg to SCIg, and immunomodulators such as azathioprine, cyclosporine, or mycophenolate mofetil may be used to reduce the IVIg dose, decrease corticosteroids, or decrease the frequency of PLEX. In some cases, for patients who continue to experience active disease, increasing the dose or frequency of treatment or combining first-line therapies may be considered. For long-term management of clinically stable patients, therapy should be periodically reduced or discontinued to assess whether further treatment is still necessary.

[0332] Despite the availability of the therapies described above, significant unmet medical needs remain for patients with CIDP. For example, while immunoglobulin therapy (IVIg, SCIg) is effective, it can be associated with significant side effects and complications such as severe headaches, thromboembolism, and hemolysis. Additionally, IVIg therapy is time-consuming and requires visits to infusion centers, as access to home health support for home administration remains limited. IVIg availability is sometimes restricted due to supply constraints. Currently available SCIg therapies typically require frequent administration via an external pump across multiple infusion sites to deliver the required dose. Corticosteroid therapy, while effective, is associated with many well-known adverse events, such as weight gain, hypertension, diabetes, and osteoporosis, especially with chronic use. PLEX is a specialized procedure requiring central venous access and is not universally available. Immunomodulatory therapies available for CIDP are all associated with significant potential risks, including the possibility of malignancy and / or infection. Others include azathioprine – cytopenia; cyclosporine – hypertension and nephrotoxicity; mycophenolate mofetil – cachexia, including neutropenia and erythrocyte (RBC) dysplasia; rituximab – nephrotoxicity; and cyclophosphamide – cardiotoxicity, pulmonary toxicity, and nephrotoxicity, as well as bone marrow suppression and infertility.

[0333] In some aspects, this disclosure provides a method for treating CIDP, the method comprising a CIDP dosing regimen (e.g., dosage, dosing frequency, etc.) that improves the therapeutic efficacy of CIDP (e.g., relative to using a different dosing regimen). In some embodiments, the method comprises administering an effective amount of an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) to a subject suffering from CIDP at a dosing frequency intended to improve therapeutic efficacy.

[0334] Various FcRn blockers (e.g., nicarlimab) have been clinically tested, and some have been FDA-approved for the treatment of CIDP (e.g., edagatimod). Anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) block FcRn-mediated IgG recycling by competitively binding to IgG binding sites on FcRn, leading to increased lysosomal degradation and decreased serum IgG levels. Therefore, in autoimmune diseases mediated by pathogenic IgG autoantibodies, FcRn blockade reduces the concentration of these antibodies. Importantly, FcRn blockade does not reduce the concentration of immunoglobulin M (IgM) or immunoglobulin A (IgA), thus preserving this part of the humoral immune system.

[0335] In some embodiments, this disclosure provides compositions (e.g., anti-FcRn antibody IMVT-1402 or battolimab) and methods (e.g., dosing regimens) for treating CIDP in subjects. In some embodiments, the subject has typical CIDP and associated clinical manifestations. In some embodiments, the subject has CIDP variants and associated clinical manifestations described herein.

[0336] In some embodiments, this disclosure provides a method (e.g., a dosing regimen) for treating a subject with CIDP, the method comprising administering an anti-FcRn antibody to the subject at a dose that effectively inhibits FcRn-mediated IgG autoantibody recirculation, thereby reducing IgG autoantibody levels (e.g., pathogenic IgG autoantibody levels).

[0337] In some embodiments, a subject with CIDP is administered an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) in the range of 200 to 400 mg. In some embodiments, a subject with CIDP is administered an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) in the range of 200 to 400 mg once weekly. In some embodiments, a subject with CIDP is administered an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) in the range of 200 to 400 mg once weekly for 20 to 60 weeks.

[0338] In some implementations, subjects with CIDP are administered anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) in the following ranges once weekly: 200-400 mg, 220-400 mg, 250-400 mg, 280-400 mg, 300-400 mg, 320-400 mg, 350-400 mg, 380-400 mg, 200-380 mg, 220-380 mg, 250-380 mg, 280-380 mg, 300-380 mg, 320-380 mg, 350-380 mg, 200-350 mg, 220-350 mg, 250-350 mg, 280-350 mg, 300-350 mg, 320-350 mg, 200-320 mg, 220-320 mg. mg, 250-320 mg, 280-320 mg, 300-320 mg, 200-300 mg, 220-300 mg, 250-300 mg, 280-300 mg, 200-280 mg, 220-280 mg, 250-280 mg, 200-250 mg, 220-250 mg, 200-220 mg. In some embodiments, IMVT-1402 is administered to subjects with CIDP at a dose of 300 mg once weekly. In some embodiments, batolimumab is administered to subjects with CIDP at a dose of 340 mg once weekly. In some embodiments, subjects with CIDP are administered 300 mg or 340 mg of an anti-FcRn antibody (e.g., IMVT-1402 or batolimumab) indefinitely. In some implementations, whether a subject with CIDP can discontinue anti-FcRn antibody (e.g., IMVT-1402 or battolimab) treatment can be assessed by improvement in one or more symptoms and / or by whether the subject gradually reduces first-line therapy (e.g., IVIg). Symptoms in subjects with CIDP can be assessed by a physician using any suitable method.

[0339] In some embodiments, a subject with CIDP is administered an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) in the range of 550 to 700 mg. In some embodiments, a subject with CIDP is administered an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) in the range of 550 to 700 mg once weekly. In some embodiments, a subject with CIDP is administered an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) in the range of 550 to 700 mg once weekly for 20 to 60 weeks.

[0340] In some implementations, subjects with CIDP are administered anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) in the following ranges once weekly: 550 to 700 mg, 550 to 690 mg, 550 to 680 mg, 550 to 670 mg, 550 to 660 mg, 550 to 650 mg, 550 to 640 mg, 550 to 630 mg, 550 to 620 mg, 550 to 610 mg, 550 to 600 mg, 550 to 590 mg, 550 to 580 mg, 550 to 570 mg, 550 to 560 mg, 580 to 700 mg, 580 to 690 mg, 580 to 680 mg, 580 to 670 mg, 580 to 660 mg, 580 to 650 mg, 580 to 640 mg, 580 to 630 mg. mg, 580 to 620 mg, 580 to 610 mg, 580 to 600 mg, 580 to 590 mg, 600 to 700 mg, 600 to 690 mg, 600 to 680 mg, 600 to 670 mg, 600 to 660 mg, 600 to 650 mg, 600 to 640 mg, 600 to 630 mg, 600 to 620 mg, 600 to 610 mg, 620 to 700 mg, 620 to 690 mg, 620 to 680 mg, 620 to 670 mg, 620 to 660 mg, 620 to 650 mg, 620 to 640 mg, 620 to 630 mg, 650 to 700 mg, 650 to 690 mg, 650 to 680 mg, 650 to 670 mg, 650 to 660 mg mg, 680 to 700 mg or 680 to 690 mg.In some implementations, IMVT-1402 is administered once weekly to subjects with CIDP in the following ranges: 550 to 700 mg, 550 to 690 mg, 550 to 680 mg, 550 to 670 mg, 550 to 660 mg, 550 to 650 mg, 550 to 640 mg, 550 to 630 mg, 550 to 620 mg, 550 to 610 mg, 550 to 600 mg, 550 to 590 mg, 550 to 580 mg, 550 to 570 mg, 550 to 560 mg, 580 to 700 mg, 580 to 690 mg, 580 to 680 mg, 580 to 670 mg, 580 to 660 mg, 580 to 650 mg, 580 to 640 mg, 580 to 630 mg, 580 to 620 mg, 580 to 610 mg. mg, 580 to 600 mg, 580 to 590 mg, 600 to 700 mg, 600 to 690 mg, 600 to 680 mg, 600 to 670 mg, 600 to 660 mg, 600 to 650 mg, 600 to 640 mg, 600 to 630 mg, 600 to 620 mg, 600 to 610 mg, 620 to 700 mg, 620 to 690 mg, 620 to 680 mg, 620 to 670 mg, 620 to 660 mg, 620 to 650 mg, 620 to 640 mg, 620 to 630 mg, 650 to 700 mg, 650 to 690 mg, 650 to 680 mg, 650 to 670 mg, 650 to 660 mg, 680 to 700 mg, or 680 to 690 mg. In some implementations, IMVT-1402 is administered to subjects with CIDP at a dose of 600 mg once a week.In some implementations, subjects with CIDP are administered battolimab in the following ranges once weekly: 550 to 700 mg, 550 to 690 mg, 550 to 680 mg, 550 to 670 mg, 550 to 660 mg, 550 to 650 mg, 550 to 640 mg, 550 to 630 mg, 550 to 620 mg, 550 to 610 mg, 550 to 600 mg, 550 to 590 mg, 550 to 580 mg, 550 to 570 mg, 550 to 560 mg, 580 to 700 mg, 580 to 690 mg, 580 to 680 mg, 580 to 670 mg, 580 to 660 mg, 580 to 650 mg, 580 to 640 mg, 580 to 630 mg, 580 to 620 mg, 580 to 610 mg. mg, 580 to 600 mg, 580 to 590 mg, 600 to 700 mg, 600 to 690 mg, 600 to 680 mg, 600 to 670 mg, 600 to 660 mg, 600 to 650 mg, 600 to 640 mg, 600 to 630 mg, 600 to 620 mg, 600 to 610 mg, 620 to 700 mg, 620 to 690 mg, 620 to 680 mg, 620 to 670 mg, 620 to 660 mg, 620 to 650 mg, 620 to 640 mg, 620 to 630 mg, 650 to 700 mg, 650 to 690 mg, 650 to 680 mg, 650 to 670 mg, 650 to 660 mg, 680 to 700 mg, or 680 to 690 mg. In some implementations, batolizumab is administered to subjects with CIDP at a dose of 680 mg once a week.

[0341] In some implementations, subjects with CIDP are administered an anti-FcRn antibody (e.g., IMVT-1402 or battolimab) at a dose ranging from 550 to 700 mg (e.g., any dose described herein) once weekly for 20 to 60 weeks, 20 to 58 weeks, 20 to 55 weeks, 20 to 52 weeks, 20 to 50 weeks, 20 to 45 weeks, 20 to 42 weeks, 20 to 40 weeks, 20 to 35 weeks, 20 to 30 weeks, 20 to 25 weeks, 25 to 60 weeks, 25 to 58 weeks, 25 to 55 weeks, 25 to 52 weeks, 25 to 50 weeks, 25 to 45 weeks, 25 to 42 weeks, 25 to 40 weeks, 25 to 35 weeks, 25 to 30 weeks, 30 to 60 weeks, 30 to 58 weeks, 30 to 55 weeks, 30 to 55 weeks, 30 to 60 weeks, 30 to 58 ...8 weeks, 30 to 60 weeks, 30 to 60 weeks, 30 to 60 weeks, 30 to 60 weeks, 30 to 60 weeks, 30 to 60 weeks, 3 52 weeks, 30 to 50 weeks, 30 to 45 weeks, 30 to 42 weeks, 30 to 40 weeks, 30 to 35 weeks, 35 to 60 weeks, 35 to 58 weeks, 35 to 55 weeks, 35 to 52 weeks, 35 to 50 weeks, 35 to 45 weeks, 35 to 42 weeks, 35 to 40 weeks, 40 to 60 weeks, 40 to 58 weeks, 40 to 55 weeks, 40 to 52 weeks, 40 to 50 weeks, 40 to 45 weeks, 40 to 42 weeks, 45 to 60 weeks, 45 to 58 weeks, 45 to 55 weeks, 45 to 52 weeks, 45 to 50 weeks, 50 to 60 weeks, 50 to 58 weeks, 50 to 55 weeks, 50 to 52 weeks, 55 to 60 weeks, or 55 to 58 weeks. In some embodiments, subjects with CIDP are administered 600 mg of IMVT-1402 for 24 weeks. In some embodiments, subjects with CIDP are administered 600 mg of IMVT-1402 for 52 weeks. In some embodiments, subjects with CIDP are administered 680 mg of battolimab for 24 weeks. In some embodiments, subjects with CIDP are administered 680 mg of battolimab for 52 weeks.

[0342] In some embodiments, after the first administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) on day 1, a loading dose of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) is administered to subjects with CIDP between days 3 and 5 of the first week of treatment. In some embodiments, the loading dose is administered to subjects with CIDP on day 4 of the first week of treatment. In some embodiments, the loading dose is 550 to 700 mg (e.g., 550 to 700 mg, 550 to 690 mg, 550 to 680 mg, 550 to 670 mg, 550 to 660 mg, 550 to 650 mg, 550 to 640 mg, 550 to 630 mg, 550 to 620 mg, 550 to 610 mg, 550 to 600 mg, 550 to 590 mg, 550 to 580 mg, 550 to 570 mg, 550 to 560 mg, 580 to 700 mg, 580 to 690 mg, 580 to 680 mg, 580 to 670 mg, 580 to 660 mg, 580 to 650 mg, 580 to 640 mg, 580 to 630 mg, 580 to 620 mg, 580 to 610 mg). mg, 580 to 600 mg, 580 to 590 mg, 600 to 700 mg, 600 to 690 mg, 600 to 680 mg, 600 to 670 mg, 600 to 660 mg, 600 to 650 mg, 600 to 640 mg, 600 to 630 mg, 600 to 620 mg, 600 to 610 mg, 620 to 700 mg, 620 to 690 mg, 620 to 680 mg, 620 to 670 mg, 620 to 660 mg, 620 to 650 mg, 620 to 640 mg, 620 to 630 mg, 650 to 700 mg, 650 to 690 mg, 650 to 680 mg, 650 to 670 mg, 650 to 660 mg, 680 to 700 mg or 680 to 690 mg The loading dose is 600 mg of anti-FcRn antibody. In some embodiments, the loading dose is 600 mg of IMVT-1402. In some embodiments, the loading dose is 680 mg of battolimab. In some embodiments, the loading dose of the anti-FcRn antibody is the same anti-FcRn antibody administered to a subject with CIDP at the same dose as weekly treatment.

[0343] In some embodiments, subjects are administered 600 mg of an anti-FcRn antibody (e.g., IMVT-1402) weekly for 24 weeks, with a loading dose of 600 mg of the anti-FcRn antibody administered on day 4 of treatment. In some embodiments, subjects with CIDP begin further anti-FcRn antibody treatment after week 24. In some embodiments, subjects receive another loading dose on days 3 through 5 of week 25. In some embodiments, subjects with CIDP receive anti-FcRn antibodies for up to an additional 52 weeks.

[0344] In some embodiments, subjects diagnosed with CIDP are suitable for the treatment described herein. In some embodiments, subjects have typical CIDP according to the European Association for Neurology / Peripheral Nerve Society (EAN / PNS) guidelines for the diagnosis and treatment of CIDP. In some embodiments, subjects with CIDP meet all of the following criteria: (i) progressive or recurrent, symmetrical, proximal and distal muscle weakness in the upper and lower extremities and sensory involvement in at least two extremities (at any point in the course of the disease); (ii) development over at least 8 weeks; (iii) absence or diminished tendon reflexes in all extremities. In some embodiments, subjects have a variant of CIDP according to the EAN / PNS guidelines for the diagnosis and treatment of CIDP. In some embodiments, subjects with a variant of CIDP meet the same clinical criteria as typical CIDP, except that tendon reflexes in unaffected extremities may be normal. In some embodiments, subjects have multifocal CIDP. In some embodiments, subjects with multifocal CIDP meet all clinical criteria for typical CIDP and also have a documented multifocal pattern of sensory loss and muscle weakness, usually asymmetrical, predominantly in the upper extremities. In some embodiments, subjects have motor CIDP. In some implementations, subjects with motor CIDP meet all the clinical criteria for typical CIDP and also have motor symptoms and signs without sensory involvement.

[0345] In addition to the clinical guidelines for CIDP, according to the EAN / PNS guidelines on the diagnosis and treatment of CIDP, individuals with CIDP also have electrodiagnostic test results that support the diagnosis of CIDP. In some implementations, subjects with CIDP meet either or both of criteria (a) or (b): (a) strongly supports the demyelinating motor nerve conduction criterion; b. weakly supports the demyelinating motor nerve conduction criterion and two or more of the following additional diagnostic criteria (e.g., based on historical data): (i) objective improvement in empirical trials of therapy using immunoglobulin, plasma exchange (PLEX), or corticosteroids; (ii) diagnostic imaging using ultrasound or magnetic resonance imaging (MRI) supporting the diagnosis of CIDP by showing nerve enlargement; (iii) cerebrospinal fluid (CSF) showing albumin cell dissociation (i.e., elevated CSF protein levels [defined as >70 mg / dL, or >10 mg / dL for subjects ≥60 years of age], and normal CSF white blood cell levels); (iv) nerve biopsy showing features supporting the diagnosis of CIDP, such as edema, demyelination, and / or onion-like spherical structures.

[0346] In some embodiments, subjects with CIDP suitable for anti-FcRn antibody therapy are currently receiving or have received corticosteroids (e.g., chronic, stable-dose systemic corticosteroids). In some embodiments, subjects with CIDP are receiving systemic corticosteroids daily. In some embodiments, subjects with CIDP are receiving systemic corticosteroids every other day. In some embodiments, subjects with CIDP are receiving systemic corticosteroids orally daily or every other day. In some embodiments, subjects with CIDP are receiving systemic corticosteroids daily or every other day via a pulsed regimen. In some embodiments, subjects using systemic corticosteroids as primary CIDP therapy are suitable for anti-FcRn antibody therapy, limited to those receiving chronic oral corticosteroids at a maximum dose equivalent to prednisolone / prednisolone 20 mg / day (including every other day or similar regimens) and willing to follow dose-gradual reduction requirements after randomization (described elsewhere herein). In oral administration, a stable dose is considered to be a daily deviation of ≤2.5 mg prednisolone or prednisolone equivalent for ≥3 months prior to administration. In some embodiments, systemic corticosteroids as primary CIDP therapy are suitable for patients receiving anti-FcRn antibody therapy, limited to those on a chronic pulsatile corticosteroid regimen defined as a dose of ≥100 mg / day of prednisolone / prednisolone equivalent (i.e., IV / IM or PO), with a minimum interval of ≥3 weeks between pulsatile treatments, and the willingness to discontinue pulsatile treatment after randomization. In pulsatile regimens, a stable dose is considered to be a repeated cycle for ≥3 months prior to administration without dose adjustment to maintain disease control.

[0347] In some embodiments, subjects with CIDP suitable for anti-FcRn antibody therapy exhibit an underlying active disease process even when symptoms are controlled (e.g., showing improvement at the start of first-line therapy or worsening after tapering of first-line therapy). In some embodiments, subjects with CIDP exhibiting an underlying active disease process meet either criterion (a) or (b) below:

[0348] (a) Within the 36 months of screening, the patient's medical record documents a clinically significant improvement following the initiation of standard care therapy, and there is clinical evidence to support ongoing disease activity. In some implementations, a clinically significant improvement may be defined as one of the following:

[0349] ○ The adjusted inflammatory neuropathy cause and treatment (aINCAT) score decreased by ≥1 point;

[0350] ○ The total score of the Inflammatory Roschön's Overall Loss of Energy Scale (I-RODS) improved by ≥4 points;

[0351] ○ Research Committee Overall Score (MRC-SS) improved by ≥3;

[0352] ○ Grip strength improvement ≥8 kPa; or

[0353] ○ Recorded in the medical record and considered a significant equivalent improvement according to the researcher's judgment.

[0354] In some implementations, evidence supporting ongoing disease activity may be any of the following (within the 12 months prior to screening):

[0355] ○ Clinical deterioration at the end of the most recent IVIG cycle; or

[0356] ○ Improved after recent IVIG infusion, or

[0357] ○ Equivalent changes in clinical status recorded in the medical record.

[0358] (b) Within the 36 months of screening, medical records documented clinically significant deterioration following reduction in standard care therapy (planned dose reduction or increased dosing interval to test for ongoing disease activity) or missed doses. In some implementations, clinically significant deterioration may be defined as one of the following:

[0359] ○aINCAT score improved by ≥1 point;

[0360] ○I-RODS total score decreased by ≥4 points;

[0361] ○MRC-SS decreased by ≥3;

[0362] ○ Grip strength deterioration ≥8 kPa; or

[0363] ○ Equivalent deterioration recorded in the medical record and considered significant by the researcher in their opinion as a significant objective measure.

[0364] In some implementations, more subjective measurements, such as changes in pain perception, will not meet the above criteria.

[0365] In some embodiments, subjects suitable for anti-FcRn antibody treatment as described herein do not have certain conditions. In some embodiments, subjects do not currently have immunoglobulin M (IgM) paraproteinemia with or without anti-myelin-associated glycoprotein antibodies, and do not have a history of such paraproteinemia. In some embodiments, subjects do not have remote CIDP. In some embodiments, subjects do not have sensory CIDP.

[0366] In some embodiments, the subject does not have focal CIDP. In some embodiments, the subject does not have remote CIDP. In some embodiments, the subject does not have autoimmune Langerhans disease, according to the EAN / PNS guidelines for the diagnosis and treatment of CIDP. In some embodiments, the subject does not have polyneuropathy of any cause other than CIDP, including but not limited to multifocal motor neuropathy; hereditary demyelinating neuropathy; polyneuropathy, organ hypertrophy, endocrine disorders, monoclonal protein and skin change syndromes; lumbosacral nerve root plexus neuropathy; systemic diseases (e.g., vitamin deficiency syndrome and neoplastic neuropathy), or drug- or toxin-induced diseases.

[0367] In some implementations, the subject does not have diabetes mellitus (DM). In some implementations, the subject shows evidence of poor DM control prior to a CIDP diagnosis (e.g., two or more instances of heme A1c (HbA1c) levels higher than 9%). In some implementations, the subject does not have poorly controlled DM at screening (e.g., two or more instances of HbA1c levels higher than 8% within the past year).

[0368] In some implementations, the subject does not suffer from spinal cord disease. In some implementations, the subject does not suffer from central demyelinating disease.

[0369] In some embodiments, the subject is receiving oral corticosteroids as primary therapy for CIDP, and the oral corticosteroids are gradually reduced upon initiation of anti-FcRn antibody (e.g., IMVT-1402 or battolimumab) therapy. In some embodiments, the subject is receiving low-dose oral corticosteroids (e.g., equivalent to 5 to 10 mg / day of prednisolone / prednisolone) and IVIg as primary therapy for CIDP, and the oral corticosteroids and / or IVIg are gradually reduced upon initiation of anti-FcRn antibody (e.g., IMVT-1402 or battolimumab) therapy.

[0370] In some embodiments, the subject is receiving pulsatile corticosteroids as primary therapy for CIDP and must interrupt treatment before the duration of anti-FcRn antibody (e.g., IMVT-1402 or battolimab) therapy is reached. In some embodiments, the subject is receiving pulsatile corticosteroids as primary therapy for CIDP and receives the last pulsatile corticosteroid 5 to 9 days (e.g., 7 days) before the first administration of anti-FcRn antibody (e.g., IMVT-1402 or battolimab) therapy.

[0371] In some embodiments, the subject is receiving immunoglobulin (Ig) therapy (e.g., IVIg or SCIg) as primary therapy for CIDP and must interrupt the treatment before the duration of anti-FcRn antibody (e.g., IMVT-1402 or battolimab) therapy is reached. In some embodiments, the subject is receiving pulsatile corticosteroids as primary therapy for CIDP and receives the last Ig therapy 5 to 9 days (e.g., 7 days) before the first administration of anti-FcRn antibody (e.g., IMVT-1402 or battolimab) therapy.

[0372] In some embodiments, subjects who did not relapse during and / or before treatment with the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) as described herein, by gradually tapering off or discontinuing first-line CIDP therapy (e.g., no relapse within the first 24 weeks of treatment with 600 mg IMVT-1402). As used herein, relapse is defined as a deterioration (improvement) of ≥1 point (e.g., at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10) in their aINCAT score relative to baseline at any point in time. Baseline aINCAT scores can be obtained prior to the first administration. In some embodiments, a subject has relapsed if the initial improvement in the aINCAT score is greater than 1 point. In some embodiments, if the initial improvement in the aINCAT score is 1 point, the subject may be further evaluated during treatment, and if the initial improvement of 1 point is maintained or increased, the subject has relapsed. The INCAT attrition scale is a widely used and validated efficacy assessment of neurological dysfunction in CIDP. Upper and lower limb dysfunction were assessed separately on a scale of 0 to 5, and the results were summed to obtain a total composite score of 0 to 10. Higher scores indicate greater disability. The minimum clinically significant difference in the INCAT disability scale is 1 point. In some embodiments, a subject is considered relapse-free if they have a decreased aINCAT score relative to baseline following anti-FcRn antibody therapy (e.g., 600 mg IMVT-1402 for 24 weeks). In some embodiments, a subject is considered relapse-free if they initially have an improved aINCAT score of 1 point above baseline, but subsequently show a decreased aINCAT score in a subsequence assessment following anti-FcRn antibody therapy (e.g., 600 mg IMVT-1402 for 24 weeks). In some embodiments, relapsed subjects do not continue anti-FcRn therapy but instead resume first-line CIDP therapy (e.g., corticosteroids and / or Ig therapy). In some embodiments, relapsed subjects continue anti-FcRn antibody therapy.

[0373] In some implementations, administration of the anti-FcRn antibody described herein (e.g., IMVT-1402 or battolimab) reduces the adjusted inflammatory neuropathy cause and treatment (aINCAT) score in subjects with CIDP.

[0374] In some implementations, administration of anti-FcRn antibodies (such as IMVT-1402 or battolimab) to subjects with CIDP increases average grip strength relative to baseline by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 100%, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, at least 10-fold, or more. Average grip strength provides an objective, quantitative, and real-time assessment of strength impairment. Jamardynamometers and Martin vigorimeters are commonly used to assess average grip strength.

[0375] In some implementations, administration of anti-FcRn antibodies (such as IMVT-1402 or battolimab) to subjects with CIDP results in an increase in the Medical Research Council Overall Score (MRC-SS) relative to the baseline MCR-SS score of at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 100%, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, at least 10-fold, or more. The MRC-SS is a standardized method for the objective assessment and reporting of muscle function. Six muscle groups were assessed bilaterally, and each muscle group was scored on a scale of 0 (no visible contraction) to 5 (normal), resulting in a total score ranging from 0 (paralysis) to 60 (normal strength).

[0376] In some implementations, administration of anti-FcRn antibodies (e.g., IMVT-1402 or battolimab) to subjects with CIDP resulted in an improvement of the Inflammatory Rosch Total Loss of Energy Scale (I-RODS) relative to the baseline I-RODS score of at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 100%, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, at least 10-fold, or more. The I-RODS for immune-mediated peripheral neuropathy is a linearly weighted scale that captures activity and social engagement limitations in participants with CIDP. It is completed by the participants in the presence or supervision of an uninformed assessor. The assessment consisted of a 24-question scale covering upper and lower limb tasks, ranging in difficulty from reading and eating to standing and running. Responses were rated on a scale of 0 to 2 (complete disability to no disability), and the raw scores were then converted into a final score ranging from 0 to 100.

[0377] In some implementations, administration of anti-FcRn antibodies (such as IMVT-1402 or battolimab) to subjects with CIDP resulted in a reduction of at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 100% in the Timed Stand-Up-Walk (TUG) test score. The TUG test is a holistic approach to measuring lower limb function, mobility, and fall risk. It requires timing the patient performing the following actions: 1. standing up from a chair, 2. walking a distance of 3 meters (approximately 10 feet), 3. turning around, 4. walking back to the chair, and 5. sitting down. The TUG demonstrates clinical improvement following intervention. The average time to complete the test varies with age and ability or the need for assistive devices. Participants with a TUG score of ≥3.5 seconds may have an increased risk of falling.

[0378] In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) described herein reduces the total IgG level (e.g., relative to baseline total IgG level before administration) of a subject with CIDP by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the subject's total IgG level (e.g., relative to baseline total IgG level before administration) by 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, and 20%. Up to 70%, 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.

[0379] In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or batolizumab) described herein reduces the levels of IgG subclasses (e.g., IgG2, IgG3, and / or IgG4) in subjects with CIDP (e.g., relative to baseline total IgG levels prior to administration) by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. In some embodiments, administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the levels of IgG subclasses (e.g., IgG1, IgG2, IgG3, or IgG4) in subjects with CIDP (e.g., relative to baseline total IgG levels before administration) by 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, 20% to 100%, 20% to 100%, 20% to 100%, 20% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 10 ... 90%, 20% to 80%, 20% to 70%, 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70% 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.

[0380] In some embodiments, the administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the level of myelin-targeting autoantibodies in subjects with CIDP (e.g., relative to baseline levels of total myelin-targeting autoantibodies prior to administration) by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. In some embodiments, administration of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the level of myelin-targeting autoantibodies (e.g., total myelin-targeting autoantibody levels relative to baseline levels prior to administration) in subjects with CIDP by 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, and 20% to 90%. 20% to 80%, 20% to 70%, 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 4 0% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.

[0381] In some embodiments, the administration regimen of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the immune complexes (IC) of a subject with CIDP (e.g., relative to baseline total IC levels before administration) by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. In some embodiments, the administration regimen of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the immune complexes (IC) of a subject with CIDP by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. (e.g., relative to the baseline total IC level before application) a reduction of 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 70%, 20% to 60%, 20% to 50%, 20% to 40%. 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.

[0382] In some embodiments, the administration regimen of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the neurociliary light chain (NfL) of a subject with CIDP (e.g., relative to baseline total NfL levels before administration) by at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, 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%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%. In some embodiments, the administration regimen of the anti-FcRn antibody (e.g., IMVT-1402 or battolimab) described herein reduces the neurociliary light chain (NfL) of a subject with CIDP. (e.g., relative to the baseline total NfL level before application) a reduction of 1% to 100%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 15%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 70%, 20% to 60%, 20% to 50%, 20% to 40%. 20% to 30%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 100%, 70% to 90%, 70% to 80%, 80% to 100%, 80% to 90%, or 90% to 100%.

[0383] Additional dosing time

[0384] The dosing regimen of anti-FcRn antibodies or antigen-binding fragments, alone or in combination with one or more additional therapeutic agents or therapies, can be adjusted to provide the optimal desired response (e.g., therapeutic response). For example, a single bolus injection of the anti-FcRn antibody or antigen-binding fragment can be administered, or several fractionated doses can be administered over a predetermined period, or the dose of the anti-FcRn antibody or antigen-binding fragment can be proportionally reduced or increased according to the urgency of the treatment situation. For any given individual, the specific dosing regimen can be adjusted over time based on the individual's needs and the professional judgment of the treating clinician. For example, in some embodiments, the dose of the anti-FcRn antibody or antigen-binding fragment can be appropriately determined by considering the patient's severity, symptoms, age, medical history, and similar factors.

[0385] The dosage of anti-FcRn antibodies or antigen-binding fragments, compositions containing anti-FcRn antibodies or antigen-binding fragments, and / or any one or more additional therapeutic agents may be selected based on the unique characteristics of one or more active compounds and the specific therapeutic effect to be achieved. A physician may start with a dose of antibody or antigen-binding fragment below the level required to achieve the desired therapeutic effect and gradually increase the dose until the desired effect is achieved. Alternatively, a physician may start with a dose of antibody or antigen-binding fragment above the level required to achieve the desired therapeutic effect and gradually decrease the dose until the desired effect is achieved. Generally, the effective dose of antibodies or antigen-binding fragments for treating autoimmune diseases can vary depending on many different factors, such as the stage of the disease, the severity of symptoms, and the prognosis of the patient. The selected dose level may also depend on a variety of pharmacokinetic factors, including the activity of the specific composition used or its esters, salts, or amides; the route of administration; the time of administration; the excretion rate of the specific compound used; the duration of treatment; other drugs, compounds, and / or materials used in combination with the specific composition used; the age, sex, weight, condition, general health status, and medical history of the patient being treated; and similar factors. In some embodiments, treatment may be administered once or several times. Given the specific symptoms of a particular patient, intermittent and / or chronic (continuous) dosing strategies may be applied.

[0386] In some embodiments, a therapeutically effective amount of anti-FcRn antibody or antigen-binding fragment is used in the methods, uses, and pharmaceutical compositions disclosed herein.

[0387] As used herein, the terms “therapeutic effective amount” and “therapeutic effective dose” interchangeably refer to an amount sufficient to reduce at least one symptom or measurable parameter associated with a disease, condition, or symptom; to normalize bodily function in a disease, condition, or symptom that causes impairment of specific bodily function; and / or to improve one or more clinically measured parameters of a disease, condition, or symptom or to slow its progression. A therapeutic effective amount may, for example, be sufficient to treat one or more symptoms of an autoimmune disease, reduce its severity, delay its onset, and / or reduce its risk. Therapeutic effective amounts and the frequency of therapeutic effective administration can be determined by methods known in the art and discussed herein. In some embodiments of the methods, uses, and compositions described herein, an anti-FcRn antibody or antigen-binding fragment is administered at a therapeutically effective amount when administered as a single agent. In some embodiments, an anti-FcRn antibody or antigen-binding fragment and at least one additional therapeutic agent are each administered at a therapeutically effective amount when used in combination. In some embodiments, a therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment is the amount required to reduce the level of total serum IgG and / or at least one autoantibody (e.g., at least one IgG) in a patient with or suspected of having an autoimmune disease.

[0388] This article provides a method for improving anti-FcRn therapy for subjects in need, comprising administering an anti-FcRn antibody to the subject. In some embodiments, the antibody or antigen-binding fragment is administered to the patient at one or more doses (e.g., two or more different doses). For example, in some embodiments, the antibody or antigen-binding fragment is administered to the patient at two different doses, such as at least one higher dose, followed by at least one lower dose.

[0389] In some aspects of this disclosure, this document provides a method for treating an autoimmune disease in a subject of need, the method comprising administering to the subject a loading dose, an induction dose, and a maintenance dose of an anti-FcRn therapy.

[0390] In some embodiments of a method for treating an autoimmune disease, the autoimmune disease is a progressive disease. In some embodiments of a method for treating an autoimmune disease, the autoimmune disease is a demyelinating disease. In some embodiments of a method for treating an autoimmune disease, the autoimmune disease is chronic inflammatory demyelinating polyneuropathy (CIDP). In some embodiments of a method for treating an autoimmune disease, the autoimmune disease is myasthenia gravis. In some embodiments of a method for treating an autoimmune disease, the autoimmune disease is Graves' disease. In some embodiments of a method for treating an autoimmune disease, the autoimmune disease is rheumatoid arthritis (e.g., refractory rheumatoid arthritis). In some embodiments of a method for treating an autoimmune disease, the autoimmune disease is systemic lupus erythematosus. In some embodiments of a method for treating an autoimmune disease, the autoimmune disease is cutaneous lupus erythematosus. In some embodiments of a method for treating an autoimmune disease, the autoimmune disease is thyroid ophthalmopathy. In some embodiments of a method for treating an autoimmune disease, the autoimmune disease is febrile autoimmune hemolytic anemia.

[0391] In some embodiments of methods for treating autoimmune diseases, the treated subject has received one or more anti-FcRn therapies. Anti-FcRn therapies may be, for example, anti-FcRn antibodies. Examples of anti-FcRn antibodies include egatimod (ARGX-113), lolixizumab (UCB7665), nicarimab (M281), orilanolimab (SYNT001), and battolimab and IMVT-1402. In some embodiments, anti-FcRn therapies comprise Abdegs, Seldegs, SYN1436, and / or SYN1327.

[0392] In some embodiments of methods for treating autoimmune diseases, the treated subject is receiving intravenous immunoglobulin (IVIg). In some embodiments of methods for treating autoimmune diseases, the treated subject is undergoing plasma exchange or plasmapheresis (PLEX).

[0393] Induction dose

[0394] The induction dose can be the dose of anti-FcRn antibody administered in the initial period to achieve control of disease symptoms.

[0395] In some embodiments, the induction dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 100 mg to about 200 mg. In some embodiments, the induction dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, or about 200 mg.

[0396] In some embodiments, the induction dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 200 mg to about 300 mg. In some embodiments, the induction dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, or about 300 mg.

[0397] In some embodiments, the induction dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 300 mg to about 500 mg. In some embodiments, the induction dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, or about 500 mg.

[0398] In some embodiments, the induction dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 500 mg to about 700 mg. In some embodiments, the induction dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, or about 700 mg.

[0399] In some embodiments, the induction dose is an anti-FcRn antibody (e.g., batopilimab or IMVT-1402) at a dose of about 700 mg to about 1000 mg. In some embodiments, the induction dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at doses of about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 765 mg, about 770 mg, about 780 mg, about 790 mg, about 800 mg, about 810 mg, about 820 mg, about 830 mg, about 840 mg, about 850 mg, about 860 mg, about 870 mg, about 880 mg, about 890 mg, about 900 mg, about 910 mg, about 920 mg, about 930 mg, about 940 mg, about 950 mg, about 960 mg, about 970 mg, about 980 mg, about 990 mg, or about 1000 mg.

[0400] In some embodiments, the induction dose is an anti-FcRn antibody (e.g., batopilimab or IMVT-1402) at a dose of about 1000 mg to about 1500 mg. In some embodiments, the induction dose is about 1000 mg, about 1010 mg, about 1020 mg, about 1030 mg, about 1040 mg, about 1050 mg, about 1060 mg, about 1070 mg, about 1080 mg, about 1090 mg, about 1100 mg, about 1110 mg, about 1120 mg, about 1130 mg, about 1140 mg, about 1150 mg, about 1160 mg, about 1170 mg, about 1180 mg, about 1190 mg, about 1200 mg, about 1210 mg, about 1220 mg, about 1230 mg, about 1240 mg, about 1250 mg, about 1260 mg, about 1270 mg, about 1280 mg, about 1290 mg, about 1300 mg, about 1310 mg, about 1320 mg, about 1330 mg, or about 1330 mg. Anti-FcRn antibodies (e.g., batolimumab or IMVT-1402) in doses of approximately 1340 mg, 1350 mg, 1360 mg, 1370 mg, 1380 mg, 1390 mg, 1400 mg, 1410 mg, 14 mg, 1430 mg, 1440 mg, 1450 mg, 1460 mg, 1470 mg, 1480 mg, 1490 mg, or 1500 mg.

[0401] In some implementations, the patient is given an induction dose of an anti-FcRn antibody (e.g., batolimumab or IMVT-1402) once or more at the following time intervals: approximately 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 ​​months, 52 months, 60 months, or longer.

[0402] In some embodiments, an induction dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once weekly. In some embodiments, an induction dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once weekly for at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 12 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 40 weeks, at least 50 weeks, at least 60 weeks, at least 70 weeks, at least 76 weeks, at least 80 weeks, or longer. In some embodiments, an induction dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once weekly for at least 12 weeks. In some embodiments, an induction dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered once weekly for at least 24 weeks.

[0403] In some embodiments, an induction dose of an anti-FcRn antibody (e.g., battolimumab or IMVT-1402) is administered to the patient once weekly as a single (i.e., once) subcutaneous injection. In some embodiments, an induction dose of an anti-FcRn antibody (e.g., battolimumab or IMVT-1402) is administered to the patient once weekly as two or more consecutive subcutaneous injections (e.g., two consecutive subcutaneous injections). As used herein, in the case of subcutaneous injection (or other routes of administration), the term "consecutive" means two or more subcutaneous injections administered one after another within a sufficiently short timeframe to provide the desired therapeutic or preventative effect. In some embodiments, consecutive subcutaneous injections are administered within approximately 30 seconds, approximately 1 minute, approximately 2 minutes, approximately 5 minutes, approximately 10 minutes, approximately 30 minutes, approximately 1 hour, approximately 2 hours, or approximately 5 hours.

[0404] In some embodiments, an induction dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient every two weeks. In some embodiments, an induction dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient every two weeks for at least 2 weeks, at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 40 weeks, at least 50 weeks, at least 60 weeks, at least 70 weeks, at least 76 weeks, at least 80 weeks, or longer. In some embodiments, an induction dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient every two weeks for at least 12 weeks. In some embodiments, an induction dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient weekly for at least 24 weeks.

[0405] In some embodiments, an induction dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once a month. In some embodiments, an induction dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once a month for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 18 months, at least 24 months, at least 30 months, at least 36 months, or longer. In some embodiments, an induction dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once a month as a single subcutaneous injection. In some embodiments, an induction dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once a month as two or more consecutive subcutaneous injections.

[0406] In some embodiments, the induction dose is a dose of 680 mg of battolimab. In some embodiments, the induction dose is a subcutaneous administration of 680 mg of battolimab once weekly. In some embodiments, the induction dose is a subcutaneous administration of 680 mg of battolimab every other week. In some embodiments, the induction dose is a subcutaneous administration of 680 mg of battolimab once weekly for 12 weeks.

[0407] In some embodiments, the induction dose is 600 mg IMVT-1402. In some embodiments, the induction dose is 600 mg IMVT-1402 administered subcutaneously once weekly. In some embodiments, the induction dose is 600 mg IMVT-1402 administered subcutaneously every other week. In some embodiments, the induction dose is 600 mg IMVT-1402 administered subcutaneously once weekly for 12 weeks.

[0408] Graves' disease (GD)

[0409] In some embodiments, the induction dose for treating Graves' disease (GD) comprises a dose of IMVT-1402 of about 100 mg to about 200 mg. In some embodiments, the induction dose for treating GD comprises a dose of IMVT-1402 of about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, or about 200 mg. In some embodiments, the induction dose for treating GD comprises a dose of IMVT-1402 of about 200 mg to about 300 mg. In some embodiments, the induction dose comprises a dose of IMVT-1402 of about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, or about 300 mg. In some embodiments, the induction dose for treating Graves' disease (GD) comprises a dose of IMVT-1402 of about 300 mg to about 500 mg. In some embodiments, the induction dose for treating GD comprises a dose of IMVT-1402 of about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, or about 500 mg. In some embodiments, the induction dose for treating GD comprises a dose of IMVT-1402 of about 500 mg to about 700 mg. In some embodiments, the induction dose for treating GD comprises IMVT-1402 in doses of about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, or about 700 mg. In some embodiments, the induction dose for treating GD comprises IMVT-1402 in doses of about 700 mg to about 1000 mg.In some embodiments, the induction dose for treating GD comprises IMVT-1402 in doses of about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 765 mg, about 770 mg, about 780 mg, about 790 mg, about 800 mg, about 810 mg, about 820 mg, about 830 mg, about 840 mg, about 850 mg, about 860 mg, about 870 mg, about 880 mg, about 890 mg, about 900 mg, about 910 mg, about 920 mg, about 930 mg, about 940 mg, about 950 mg, about 960 mg, about 970 mg, about 980 mg, about 990 mg, or about 1000 mg. In some embodiments, the induction dose for treating GD comprises a dose of IMVT-1402 of about 1000 mg to about 1500 mg. In some embodiments, the induction dose for treating GD includes about 1000 mg, about 1010 mg, about 1020 mg, about 1030 mg, about 1040 mg, about 1050 mg, about 1060 mg, about 1070 mg, about 1080 mg, about 1090 mg, about 1100 mg, about 1110 mg, about 1120 mg, about 1130 mg, about 1140 mg, about 1150 mg, about 1160 mg, about 1170 mg, about 1180 mg, about 1190 mg, about 1200 mg, about 1210 mg, about 1220 mg, about 1230 mg, about 1240 mg, about 1250 mg, about 1260 mg, about 1270 mg, about 1280 mg, about 1290 mg, about 1300 mg, about 1310 mg, and about 1320 mg. IMVT-1402 in doses of approximately 1330 mg, 1340 mg, 1350 mg, 1360 mg, 1370 mg, 1380 mg, 1390 mg, 1400 mg, 1410 mg, 1420 mg, 1430 mg, 1440 mg, 1450 mg, 1460 mg, 1470 mg, 1480 mg, 1490 mg, or 1500 mg.

[0410] In some implementations, the induction dose of IMVT-1402 for treating GD is administered to the patient once or more during the following time periods: approximately 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 ​​months, 52 months, 60 months, or longer.

[0411] In some embodiments, an induction dose of IMVT-1402 for treating GD is administered to the patient once weekly. In some embodiments, an induction dose of IMVT-1402 for treating GD is administered to the patient once weekly for at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 12 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 40 weeks, at least 50 weeks, at least 60 weeks, at least 70 weeks, at least 76 weeks, at least 80 weeks, or longer. In some embodiments, an induction dose of IMVT-1402 for treating GD is administered to the patient once weekly for at least 12 weeks. In some embodiments, an induction dose of IMVT-1402 for treating GD is administered once weekly for at least 24 weeks.

[0412] In some embodiments, an induction dose of IMVT-1402 for treating GD is administered to a patient once weekly as a single (i.e., once) subcutaneous injection. In some embodiments, an induction dose of IMVT-1402 for treating GD is administered to a patient once weekly as two or more consecutive subcutaneous injections (e.g., two consecutive subcutaneous injections). As used herein, in the case of subcutaneous injection (or other routes of administration), the term "consecutive" means two or more subcutaneous injections administered one after another within a sufficiently short timeframe to provide the desired therapeutic or preventative effect. In some embodiments, consecutive subcutaneous injections are administered within approximately 30 seconds, approximately 1 minute, approximately 2 minutes, approximately 5 minutes, approximately 10 minutes, approximately 30 minutes, approximately 1 hour, approximately 2 hours, or approximately 5 hours.

[0413] In some embodiments, an induction dose of IMVT-1402 for treating GD is administered to the patient every two weeks. In some embodiments, an induction dose of IMVT-1402 for treating GD is administered to the patient every two weeks for at least 2 weeks, at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 40 weeks, at least 50 weeks, at least 60 weeks, at least 70 weeks, at least 76 weeks, at least 80 weeks, or longer. In some embodiments, an induction dose of IMVT-1402 for treating GD is administered to the patient every two weeks for at least 12 weeks. In some embodiments, an induction dose of IMVT-1402 for treating GD is administered to the patient weekly for at least 24 weeks.

[0414] In some embodiments, an induction dose of IMVT-1402 for treating GD is administered to the patient once a month. In some embodiments, an induction dose of IMVT-1402 for treating GD is administered to the patient once a month for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 18 months, at least 24 months, at least 30 months, at least 36 months, or longer. In some embodiments, an induction dose of IMVT-1402 for treating GD is administered to the patient once a month as a single subcutaneous injection. In some embodiments, an induction dose of IMVT-1402 for treating GD is administered to the patient once a month as two or more consecutive subcutaneous injections.

[0415] In some embodiments, the induction dose for treating GD is 600 mg IMVT-1402. In some embodiments, the induction dose for treating GD is 600 mg IMVT-1402 administered subcutaneously once weekly. In some embodiments, the induction dose for treating GD is 600 mg IMVT-1402 administered subcutaneously every other week. In some embodiments, the induction dose for treating GD is 600 mg IMVT-1402 administered subcutaneously once weekly for 26 weeks. In some embodiments, the induction dose for treating GD is 600 mg IMVT-1402 administered subcutaneously once weekly for 52 weeks. In some implementations, the induction dose of IMVT-1402 for treating GD is combined with a burst dose for treating GD (e.g., a parallel or additional dose of IMVT-1402 for controlling GD bursts).

[0416] Rheumatoid arthritis (RA)

[0417] In some embodiments, the induction dose for treating rheumatoid arthritis (RA) comprises a dose of IMVT-1402 of about 100 mg to about 200 mg. In some embodiments, the induction dose for treating RA comprises a dose of IMVT-1402 of about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, or about 200 mg. In some embodiments, the induction dose for treating RA comprises a dose of IMVT-1402 of about 200 mg to about 300 mg. In some embodiments, the induction dose comprises a dose of IMVT-1402 of about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, or about 300 mg. In some embodiments, the induction dose for treating RA comprises a dose of IMVT-1402 of about 300 mg to about 500 mg. In some embodiments, the induction dose for treating RA comprises a dose of IMVT-1402 of about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, or about 500 mg. In some embodiments, the induction dose for treating RA comprises a dose of IMVT-1402 of about 500 mg to about 700 mg. In some embodiments, the induction dose for treating RA comprises IMVT-1402 in doses of about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, or about 700 mg. In some embodiments, the induction dose for treating RA comprises IMVT-1402 in doses of about 700 mg to about 1000 mg.In some embodiments, the induction dose for treating RA comprises IMVT-1402 in doses of about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 765 mg, about 770 mg, about 780 mg, about 790 mg, about 800 mg, about 810 mg, about 820 mg, about 830 mg, about 840 mg, about 850 mg, about 860 mg, about 870 mg, about 880 mg, about 890 mg, about 900 mg, about 910 mg, about 920 mg, about 930 mg, about 940 mg, about 950 mg, about 960 mg, about 970 mg, about 980 mg, about 990 mg, or about 1000 mg. In some embodiments, the induction dose for treating RA comprises a dose of IMVT-1402 of about 1000 mg to about 1500 mg. In some embodiments, the induction dose for treating RA includes about 1000 mg, about 1010 mg, about 1020 mg, about 1030 mg, about 1040 mg, about 1050 mg, about 1060 mg, about 1070 mg, about 1080 mg, about 1090 mg, about 1100 mg, about 1110 mg, about 1120 mg, about 1130 mg, about 1140 mg, about 1150 mg, about 1160 mg, about 1170 mg, about 1180 mg, about 1190 mg, about 1200 mg, about 1210 mg, about 1220 mg, about 1230 mg, about 1240 mg, about 1250 mg, about 1260 mg, about 1270 mg, about 1280 mg, about 1290 mg, about 1300 mg, about 1310 mg, and about 1320 mg. IMVT-1402 in doses of approximately 1330 mg, 1340 mg, 1350 mg, 1360 mg, 1370 mg, 1380 mg, 1390 mg, 1400 mg, 1410 mg, 1420 mg, 1430 mg, 1440 mg, 1450 mg, 1460 mg, 1470 mg, 1480 mg, 1490 mg, or 1500 mg.

[0418] In some implementations, the induction dose of IMVT-1402 for the treatment of RA is administered to the patient once or more during the following time periods: approximately 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 ​​months, 52 months, 60 months, or longer.

[0419] In some embodiments, an induction dose of IMVT-1402 for treating RA is administered to the patient once weekly. In some embodiments, an induction dose of IMVT-1402 for treating RA is administered to the patient once weekly for at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 12 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 40 weeks, at least 50 weeks, at least 60 weeks, at least 70 weeks, at least 76 weeks, at least 80 weeks, or longer. In some embodiments, an induction dose of IMVT-1402 for treating RA is administered to the patient once weekly for at least 12 weeks. In some embodiments, an induction dose of IMVT-1402 for treating RA is administered once weekly for at least 24 weeks.

[0420] In some embodiments, an induction dose of IMVT-1402 for the treatment of RA is administered to a patient once weekly as a single (i.e., once) subcutaneous injection. In some embodiments, an induction dose of IMVT-1402 for the treatment of RA is administered to a patient once weekly as two or more consecutive subcutaneous injections (e.g., two consecutive subcutaneous injections). As used herein, in the case of subcutaneous injection (or other routes of administration), the term "consecutive" means two or more subcutaneous injections administered one after another within a sufficiently short timeframe to provide the desired therapeutic or preventative effect. In some embodiments, consecutive subcutaneous injections are administered within approximately 30 seconds, approximately 1 minute, approximately 2 minutes, approximately 5 minutes, approximately 10 minutes, approximately 30 minutes, approximately 1 hour, approximately 2 hours, or approximately 5 hours.

[0421] In some embodiments, an induction dose of IMVT-1402 for treating RA is administered to the patient every two weeks. In some embodiments, an induction dose of IMVT-1402 for treating RA is administered to the patient every two weeks for at least 2 weeks, at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 40 weeks, at least 50 weeks, at least 60 weeks, at least 70 weeks, at least 76 weeks, at least 80 weeks, or longer. In some embodiments, an induction dose of IMVT-1402 for treating RA is administered to the patient every two weeks for at least 12 weeks. In some embodiments, an induction dose of IMVT-1402 for treating RA is administered to the patient weekly for at least 24 weeks.

[0422] In some embodiments, an induction dose of IMVT-1402 for treating RA is administered to the patient once a month. In some embodiments, an induction dose of IMVT-1402 for treating RA is administered to the patient once a month for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 18 months, at least 24 months, at least 30 months, at least 36 months, or longer. In some embodiments, an induction dose of IMVT-1402 for treating RA is administered to the patient once a month as a single subcutaneous injection. In some embodiments, an induction dose of IMVT-1402 for treating RA is administered to the patient once a month as two or more consecutive subcutaneous injections.

[0423] In some embodiments, the induction dose for treating RA is 600 mg IMVT-1402. In some embodiments, the induction dose for treating RA is 600 mg IMVT-1402 administered subcutaneously once weekly. In some embodiments, the induction dose for treating RA is 600 mg IMVT-1402 administered subcutaneously every other week. In some embodiments, the induction dose for treating RA is 600 mg IMVT-1402 administered subcutaneously once weekly for 16 weeks. In some embodiments, the induction dose for treating RA is 600 mg IMVT-1402 administered subcutaneously once weekly for 16 weeks. In some embodiments, the induction dose for treating RA is 600 mg IMVT-1402 administered subcutaneously once weekly for 32 weeks. In some embodiments, the induction dose for treating RA is 600 mg IMVT-1402 administered subcutaneously once weekly for 16 weeks, after which the induction dose is discontinued and a maintenance dose is administered. In some implementations, an induction dose of IMVT-1402 for treating RA is combined with a burst dose for treating RA (e.g., a parallel or additional dose of IMVT-1402 for controlling RA bursts).

[0424] Maintenance dose

[0425] The maintenance dose can be a lower dose of the anti-FcRn antibody (compared to the induction dose), administered after the initial induction dose to maintain control of disease symptoms. However, in some cases, the induction dose and maintenance dose can be the same or similar.

[0426] In some embodiments, a maintenance dose of the anti-FcRn antibody (e.g., battolimab or IMVT-1402) is taken at a dose of about 100 mg to about 200 mg. In some embodiments, a maintenance dose of the anti-FcRn antibody (e.g., battolimab or IMVT-1402) is taken at a dose of about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, or about 200 mg.

[0427] In some embodiments, a maintenance dose of the anti-FcRn antibody (e.g., battolimab or IMVT-1402) is taken at a dose of about 200 mg to about 300 mg. In some embodiments, a maintenance dose of the anti-FcRn antibody (e.g., battolimab or IMVT-1402) is taken at a dose of about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, or about 300 mg.

[0428] In some embodiments, a maintenance dose of the anti-FcRn antibody (e.g., battolimab or IMVT-1402) is taken at a dose of about 300 mg to about 500 mg. In some embodiments, a maintenance dose of the anti-FcRn antibody (e.g., battolimab or IMVT-1402) is taken at a dose of about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, or about 500 mg.

[0429] In some embodiments, the maintenance dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 500 mg to about 700 mg. In some embodiments, the maintenance dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, or about 700 mg.

[0430] In some embodiments, a maintenance dose of the anti-FcRn antibody (e.g., batopilimab or IMVT-1402) is maintained at a dose of about 700 mg to about 1000 mg. In some embodiments, the maintenance dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at doses of about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 765 mg, about 770 mg, about 780 mg, about 790 mg, about 800 mg, about 810 mg, about 820 mg, about 830 mg, about 840 mg, about 850 mg, about 860 mg, about 870 mg, about 880 mg, about 890 mg, about 900 mg, about 910 mg, about 920 mg, about 930 mg, about 940 mg, about 950 mg, about 960 mg, about 970 mg, about 980 mg, about 990 mg, or about 1000 mg.

[0431] In some embodiments, a maintenance dose of the anti-FcRn antibody (e.g., batopilimab or IMVT-1402) is maintained at about 1000 mg to about 1500 mg. In some embodiments, the maintenance dose is about 1000 mg, about 1010 mg, about 1020 mg, about 1030 mg, about 1040 mg, about 1050 mg, about 1060 mg, about 1070 mg, about 1080 mg, about 1090 mg, about 1100 mg, about 1110 mg, about 1120 mg, about 1130 mg, about 1140 mg, about 1150 mg, about 1160 mg, about 1170 mg, about 1180 mg, about 1190 mg, about 1200 mg, about 1210 mg, about 1220 mg, about 1230 mg, about 1240 mg, about 1250 mg, about 1260 mg, about 1270 mg, about 1280 mg, about 1290 mg, about 1300 mg, about 1310 mg, about 1320 mg, about 1330 mg, or about 1330 mg. Anti-FcRn antibodies (e.g., batopilimab or IMVT-1402) in doses of approximately 1340 mg, 1350 mg, 1360 mg, 1370 mg, 1380 mg, 1390 mg, 1400 mg, 1410 mg, 1420 mg, 1430 mg, 1440 mg, 1450 mg, 1460 mg, 1470 mg, 1480 mg, 1490 mg, or 1500 mg.

[0432] In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., batopilimab or IMVT-1402) is administered to the patient once or more during the following time periods: approximately 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 ​​months, 52 months, 60 months, or longer. In some embodiments, the maintenance dose is administered for the remainder of the patient's life.

[0433] In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once weekly. In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once weekly for at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 12 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 40 weeks, at least 50 weeks, at least 60 weeks, at least 70 weeks, at least 76 weeks, at least 80 weeks, or longer. In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once weekly for at least 12 weeks. In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered once weekly for at least 24 weeks.

[0434] In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once weekly via a single (i.e., one) subcutaneous injection. In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once weekly via two or more consecutive subcutaneous injections (e.g., two consecutive subcutaneous injections).

[0435] In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient every two weeks. In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient every two weeks for at least 2 weeks, at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 40 weeks, at least 50 weeks, at least 60 weeks, at least 70 weeks, at least 76 weeks, at least 80 weeks, or longer. In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient every two weeks for at least 12 weeks. In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient weekly for at least 24 weeks.

[0436] In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once a month. In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once a month for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 18 months, at least 24 months, at least 30 months, at least 36 months, or longer. In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once a month via a single subcutaneous injection. In some embodiments, a maintenance dose of an anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient once a month via two or more consecutive subcutaneous injections.

[0437] In some embodiments, the maintenance dose is 340 mg of battolimab. In some embodiments, the maintenance dose is 340 mg of battolimab administered subcutaneously once weekly. In some embodiments, the maintenance dose is 340 mg of battolimab administered subcutaneously every other week. In some embodiments, the maintenance dose is 340 mg of battolimab administered subcutaneously once weekly for 12 months or longer. In some embodiments, the maintenance dose is 340 mg of battolimab administered subcutaneously every other week for 12 months or longer.

[0438] In some embodiments, the maintenance dose is 680 mg of battolimab. In some embodiments, the maintenance dose is 680 mg of battolimab administered subcutaneously once weekly. In some embodiments, the maintenance dose is 680 mg of battolimab administered subcutaneously every other week. In some embodiments, the maintenance dose is 680 mg of battolimab administered subcutaneously once weekly for 12 months or longer. In some embodiments, the maintenance dose is 680 mg of battolimab administered subcutaneously every other week for 12 months or longer.

[0439] In some embodiments, the maintenance dose is 300 mg IMVT-1402. In some embodiments, the maintenance dose is 300 mg IMVT-1402 administered subcutaneously once weekly. In some embodiments, the maintenance dose is 300 mg IMVT-1402 administered subcutaneously every other week. In some embodiments, the maintenance dose is 300 mg IMVT-1402 administered subcutaneously once weekly for 12 months or longer. In some embodiments, the maintenance dose is 300 mg IMVT-1402 administered subcutaneously every other week for 12 months or longer.

[0440] In some embodiments, the maintenance dose is 600 mg IMVT-1402. In some embodiments, the maintenance dose is 600 mg IMVT-1402 administered subcutaneously once weekly. In some embodiments, the maintenance dose is 600 mg IMVT-1402 administered subcutaneously every other week. In some embodiments, the maintenance dose is 600 mg IMVT-1402 administered subcutaneously once weekly for 12 months or longer. In some embodiments, the maintenance dose is 600 mg IMVT-1402 administered subcutaneously every other week for 12 months or longer.

[0441] In some embodiments, the induction dose and maintenance dose are alternated; for example, the patient may receive an induction dose for a first period, followed by a maintenance dose for a first period, then an induction dose for a second period, optionally followed by a maintenance dose for a second period. In some embodiments, the cycle of induction and maintenance doses (one cycle consisting of administering an induction dose for a period followed by administering a maintenance dose for a period) is repeated once, twice, three times, four times, five times, six times, seven times, or ten times. In some embodiments, the cycle of induction and maintenance doses is repeated for approximately 3 months, approximately 6 months, approximately 12 months, approximately 15 months, approximately 18 months, approximately 24 months, or longer.

[0442] In another aspect, the method described herein comprises (i) administering 680 mg of anti-FcRn antibody subcutaneously to the subject once weekly for 12 weeks, followed by (ii) administering 340 mg of anti-FcRn antibody subcutaneously to the subject once weekly for 12 weeks. In yet another aspect, the method described herein comprises (i) administering 600 mg of anti-FcRn antibody subcutaneously to the subject once weekly for 12 weeks, followed by (ii) administering 300 mg of anti-FcRn antibody subcutaneously to the subject once weekly for 12 weeks. These steps (i) and (ii) may be repeated as needed, for example, twice (total treatment time 48 weeks), three times (total treatment time 72 weeks), four times (total treatment time 96 weeks), or five times (total treatment time 120 weeks).

[0443] Graves' disease (GD)

[0444] The maintenance dose for treating Graves' disease (GD) may be a lower dose of IMVT-1402 (compared to the induction dose), administered after the initial induction dose to maintain control of disease symptoms. In some embodiments, the maintenance dose for treating GD comprises the same dose as the induction dose for treating GD.

[0445] In some embodiments, the maintenance dose of IMVT-1402 for treating GD is a dose of about 100 mg to about 200 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating GD is a dose of about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, or about 200 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating GD is a dose of about 200 mg to about 300 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating GD is a dose of about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, or about 300 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating GD is a dose of about 300 mg to about 500 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating GD is a dose of about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, or about 500 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating GD is a dose of about 500 mg to about 700 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating GD is a dose of about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, or about 700 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating GD is a dose of about 700 mg to about 1000 mg.In some embodiments, the maintenance dose of IMVT-1402 for treating GD is approximately 700 mg, approximately 710 mg, approximately 720 mg, approximately 730 mg, approximately 740 mg, approximately 750 mg, approximately 760 mg, approximately 765 mg, approximately 770 mg, approximately 780 mg, approximately 790 mg, approximately 800 mg, approximately 810 mg, approximately 820 mg, approximately 830 mg, approximately 840 mg, approximately 850 mg, approximately 860 mg, approximately 870 mg, approximately 880 mg, approximately 890 mg, approximately 900 mg, approximately 910 mg, approximately 920 mg, approximately 930 mg, approximately 940 mg, approximately 950 mg, approximately 960 mg, approximately 970 mg, approximately 980 mg, approximately 990 mg, or approximately 1000 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating GD is a dose of about 1000 mg to about 1500 mg. In some embodiments, the maintenance dose for treating GD is about 1000 mg, about 1010 mg, about 1020 mg, about 1030 mg, about 1040 mg, about 1050 mg, about 1060 mg, about 1070 mg, about 1080 mg, about 1090 mg, about 1100 mg, about 1110 mg, about 1120 mg, about 1130 mg, about 1140 mg, about 1150 mg, about 1160 mg, about 1170 mg, about 1180 mg, about 1190 mg, about 1200 mg, about 1210 mg, about 1220 mg, about 1230 mg, about 1240 mg, about 1250 mg, about 1260 mg, about 1270 mg, about 1280 mg, about 1290 mg, about 1300 mg, about 1310 mg, or about 1310 mg. IMVT-1402 in doses of approximately 1320 mg, approximately 1330 mg, approximately 1340 mg, approximately 1350 mg, approximately 1360 mg, approximately 1370 mg, approximately 1380 mg, approximately 1390 mg, approximately 1400 mg, approximately 1410 mg, approximately 1420 mg, approximately 1430 mg, approximately 1440 mg, approximately 1450 mg, approximately 1460 mg, approximately 1470 mg, approximately 1480 mg, approximately 1490 mg, or approximately 1500 mg.

[0446] In some embodiments, the maintenance dose of IMVT-1402 for treating GD is administered to the patient once or more during the following time periods: approximately 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 ​​months, 52 months, 60 months, or longer. In some embodiments, the maintenance dose for treating GD is administered to the patient for the remainder of their life.

[0447] In some embodiments, a maintenance dose of IMVT-1402 for treating GD is administered to the patient once weekly. In some embodiments, a maintenance dose of IMVT-1402 for treating GD is administered to the patient once weekly for at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 12 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 40 weeks, at least 50 weeks, at least 60 weeks, at least 70 weeks, at least 76 weeks, at least 80 weeks, or longer. In some embodiments, a maintenance dose of IMVT-1402 for treating GD is administered to the patient once weekly for at least 12 weeks. In some embodiments, a maintenance dose of IMVT-1402 for treating GD is administered once weekly for at least 24 weeks.

[0448] In some embodiments, IMVT-1402 is administered to the patient once a week as a maintenance dose for treating GD via a single (i.e., one) subcutaneous injection. In some embodiments, IMVT-1402 is administered to the patient once a week as a maintenance dose for treating GD via two or more consecutive subcutaneous injections (e.g., two consecutive subcutaneous injections).

[0449] In some embodiments, a maintenance dose of IMVT-1402 for treating GD is administered to the patient every two weeks. In some embodiments, a maintenance dose of IMVT-1402 for treating GD is administered to the patient every two weeks for at least 2 weeks, at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 40 weeks, at least 50 weeks, at least 60 weeks, at least 70 weeks, at least 76 weeks, at least 80 weeks, or longer. In some embodiments, a maintenance dose of IMVT-1402 for treating GD is administered to the patient every two weeks for at least 12 weeks. In some embodiments, a maintenance dose of IMVT-1402 for treating GD is administered to the patient weekly for at least 24 weeks.

[0450] In some embodiments, a maintenance dose of IMVT-1402 for treating GD is administered to the patient once a month. In some embodiments, a maintenance dose of IMVT-1402 for treating GD is administered to the patient once a month for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 18 months, at least 24 months, at least 30 months, at least 36 months, or longer. In some embodiments, a maintenance dose of IMVT-1402 for treating GD is administered to the patient once a month as a single subcutaneous injection. In some embodiments, a maintenance dose of IMVT-1402 for treating GD is administered to the patient once a month as two or more consecutive subcutaneous injections.

[0451] In some embodiments, the maintenance dose for treating Graves' disease (GD) comprises a dose of 300 mg of IMVT-1402 administered subcutaneously once weekly. In some embodiments, the maintenance dose for treating GD comprises a dose of 300 mg of IMVT-1402 administered subcutaneously every other week. In some embodiments, the maintenance dose for treating GD comprises a dose of 300 mg of IMVT-1402 administered subcutaneously once weekly for 12 months or longer. In some embodiments, the maintenance dose for treating GD comprises a dose of 300 mg of IMVT-1402 administered subcutaneously every other week for 12 months or longer.

[0452] In some embodiments, the maintenance dose for treating Graves' disease (GD) comprises a dose of 600 mg of IMVT-1402 administered subcutaneously once weekly. In some embodiments, the maintenance dose for treating GD comprises a dose of 600 mg of IMVT-1402 administered subcutaneously every other week. In some embodiments, the maintenance dose for treating GD comprises a dose of 600 mg of IMVT-1402 administered subcutaneously once weekly for 12 months or longer. In some embodiments, the maintenance dose for treating GD comprises a dose of 600 mg of IMVT-1402 administered subcutaneously every other week for 12 months or longer.

[0453] In some embodiments, the induction dose and the maintenance dose for treating GD are alternated. For example, the patient may receive an induction dose for a first period, followed by a maintenance dose for treating GD for a first period, then an induction dose for a second period, optionally followed by a maintenance dose for treating GD for a second period. In some embodiments, the cycle of induction and maintenance doses (one cycle consisting of administering an induction dose for a period followed by administering a maintenance dose for treating GD for a period) is repeated once, twice, three times, four times, five times, six times, seven times, or ten times. In some embodiments, the cycle of induction and maintenance doses is repeated for approximately 3 months, approximately 6 months, approximately 12 months, approximately 15 months, approximately 18 months, approximately 24 months, or longer.

[0454] In another aspect, the method described herein comprises (i) administering 600 mg IMVT-1402 subcutaneously to the subject once weekly for 26 weeks, followed by (ii) administering 300 mg IMVT-1402 subcutaneously to the subject once weekly for 26 weeks. These steps (i) and (ii) may be repeated as needed, for example, twice (total treatment time 52 weeks), three times (total treatment time 78 weeks), four times (total treatment time 104 weeks), or five times (total treatment time 130 weeks).

[0455] In some embodiments, the maintenance dose for treating GD comprises a dose of 600 mg IMVT-1402 administered subcutaneously once weekly for 26 weeks. In some embodiments, the maintenance dose for treating GD comprises a dose of 600 mg IMVT-1402 administered subcutaneously once weekly for 52 weeks. In some embodiments, the maintenance dose for treating GD comprises a dose of 600 mg IMVT-1402 administered subcutaneously once weekly for at least 52 weeks. In some embodiments, the maintenance dose of IMVT-1402 for treating GD is combined with a burst dose for treating GD (e.g., a parallel or additional dose of IMVT-1402 used to control GD bursts).

[0456] Rheumatoid arthritis (RA)

[0457] The maintenance dose for treating rheumatoid arthritis (RA) may be a lower dose of IMVT-1402 (compared to the induction dose), administered after the initial induction dose to maintain control of disease symptoms. In some embodiments, the maintenance dose for treating RA comprises the same dose as the induction dose for treating RA.

[0458] In some embodiments, the maintenance dose of IMVT-1402 for treating RA is a dose of about 100 mg to about 200 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating RA is a dose of about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, or about 200 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating RA is a dose of about 200 mg to about 300 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating RA is a dose of about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, or about 300 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating RA is a dose of about 300 mg to about 500 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating RA is a dose of about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, or about 500 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating RA is a dose of about 500 mg to about 700 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating RA is a dose of about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, or about 700 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating RA is a dose of about 700 mg to about 1000 mg.In some embodiments, the maintenance dose of IMVT-1402 for treating RA is approximately 700 mg, approximately 710 mg, approximately 720 mg, approximately 730 mg, approximately 740 mg, approximately 750 mg, approximately 760 mg, approximately 765 mg, approximately 770 mg, approximately 780 mg, approximately 790 mg, approximately 800 mg, approximately 810 mg, approximately 820 mg, approximately 830 mg, approximately 840 mg, approximately 850 mg, approximately 860 mg, approximately 870 mg, approximately 880 mg, approximately 890 mg, approximately 900 mg, approximately 910 mg, approximately 920 mg, approximately 930 mg, approximately 940 mg, approximately 950 mg, approximately 960 mg, approximately 970 mg, approximately 980 mg, approximately 990 mg, or approximately 1000 mg. In some embodiments, the maintenance dose of IMVT-1402 for treating RA is a dose of about 1000 mg to about 1500 mg. In some embodiments, the maintenance dose for treating RA is about 1000 mg, about 1010 mg, about 1020 mg, about 1030 mg, about 1040 mg, about 1050 mg, about 1060 mg, about 1070 mg, about 1080 mg, about 1090 mg, about 1100 mg, about 1110 mg, about 1120 mg, about 1130 mg, about 1140 mg, about 1150 mg, about 1160 mg, about 1170 mg, about 1180 mg, about 1190 mg, about 1200 mg, about 1210 mg, about 1220 mg, about 1230 mg, about 1240 mg, about 1250 mg, about 1260 mg, about 1270 mg, about 1280 mg, about 1290 mg, about 1300 mg, about 1310 mg, or about 1210 mg. IMVT-1402 in doses of approximately 1320 mg, approximately 1330 mg, approximately 1340 mg, approximately 1350 mg, approximately 1360 mg, approximately 1370 mg, approximately 1380 mg, approximately 1390 mg, approximately 1400 mg, approximately 1410 mg, approximately 1420 mg, approximately 1430 mg, approximately 1440 mg, approximately 1450 mg, approximately 1460 mg, approximately 1470 mg, approximately 1480 mg, approximately 1490 mg, or approximately 1500 mg.

[0459] In some embodiments, the maintenance dose of IMVT-1402 for the treatment of RA is administered to the patient once or more during the following time periods: approximately 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 ​​months, 52 months, 60 months, or longer. In some embodiments, the maintenance dose for the treatment of RA is administered to the patient for the remainder of their life.

[0460] In some embodiments, a maintenance dose of IMVT-1402 for treating RA is administered to the patient once weekly. In some embodiments, a maintenance dose of IMVT-1402 for treating RA is administered to the patient once weekly for at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 12 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 40 weeks, at least 50 weeks, at least 60 weeks, at least 70 weeks, at least 76 weeks, at least 80 weeks, or longer. In some embodiments, a maintenance dose of IMVT-1402 for treating RA is administered to the patient once weekly for at least 12 weeks. In some embodiments, a maintenance dose of IMVT-1402 for treating RA is administered once weekly for at least 24 weeks. In some embodiments, a maintenance dose of IMVT-1402 for treating GD is administered once weekly for at least 52 weeks.

[0461] In some embodiments, IMVT-1402 is administered to the patient once a week as a maintenance dose for the treatment of RA via a single (i.e., one) subcutaneous injection. In some embodiments, IMVT-1402 is administered to the patient once a week as a maintenance dose for the treatment of RA via two or more consecutive subcutaneous injections (e.g., two consecutive subcutaneous injections).

[0462] In some embodiments, a maintenance dose of IMVT-1402 for treating RA is administered to the patient every two weeks. In some embodiments, a maintenance dose of IMVT-1402 for treating RA is administered to the patient every two weeks for at least 2 weeks, at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 40 weeks, at least 50 weeks, at least 60 weeks, at least 70 weeks, at least 76 weeks, at least 80 weeks, or longer. In some embodiments, a maintenance dose of IMVT-1402 for treating RA is administered to the patient every two weeks for at least 12 weeks. In some embodiments, a maintenance dose of IMVT-1402 for treating RA is administered to the patient weekly for at least 24 weeks.

[0463] In some embodiments, a maintenance dose of IMVT-1402 for treating RA is administered to the patient once a month. In some embodiments, a maintenance dose of IMVT-1402 for treating RA is administered to the patient once a month for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 18 months, at least 24 months, at least 30 months, at least 36 months, or longer. In some embodiments, a maintenance dose of IMVT-1402 for treating RA is administered to the patient once a month as a single subcutaneous injection. In some embodiments, a maintenance dose of IMVT-1402 for treating RA is administered to the patient once a month as two or more consecutive subcutaneous injections.

[0464] In some embodiments, the maintenance dose for treating RA comprises a dose of 300 mg of IMVT-1402 administered subcutaneously once weekly. In some embodiments, the maintenance dose for treating RA comprises a dose of 300 mg of IMVT-1402 administered subcutaneously every other week. In some embodiments, the maintenance dose for treating RA comprises a dose of 300 mg of IMVT-1402 administered subcutaneously once weekly for 12 months or longer. In some embodiments, the maintenance dose for treating RA comprises a dose of 300 mg of IMVT-1402 administered subcutaneously every other week for 12 months or longer.

[0465] In some embodiments, the maintenance dose for treating RA comprises a dose of 600 mg of IMVT-1402 administered subcutaneously once weekly. In some embodiments, the maintenance dose for treating RA comprises a dose of 600 mg of IMVT-1402 administered subcutaneously every other week. In some embodiments, the maintenance dose for treating RA comprises a dose of 600 mg of IMVT-1402 administered subcutaneously once weekly for 12 months or longer. In some embodiments, the maintenance dose for treating RA comprises a dose of 600 mg of IMVT-1402 administered subcutaneously every other week for 12 months or longer.

[0466] In some embodiments, the induction dose and the maintenance dose for treating RA are alternated. For example, a patient may receive an induction dose for a first period, followed by a maintenance dose for treating RA for a first period, then an induction dose for a second period, optionally followed by a maintenance dose for treating RA for a second period. In some embodiments, the cycle of induction and maintenance doses (one cycle consisting of administering an induction dose for a period followed by administering a maintenance dose for treating RA for a period) is repeated once, twice, three times, four times, five times, six times, seven times, or ten times. In some embodiments, the cycle of induction and maintenance doses is repeated for approximately 3 months, approximately 6 months, approximately 12 months, approximately 15 months, approximately 18 months, approximately 24 months, or longer.

[0467] In another aspect, the method described herein comprises (i) administering 600 mg IMVT-1402 subcutaneously to the subject once weekly for 16 weeks, followed by (ii) administering 300 mg IMVT-1402 subcutaneously to the subject once weekly for 16 weeks. These steps (i) and (ii) may be repeated as needed, for example, twice (total treatment time 32 weeks), three times (total treatment time 48 weeks), four times (total treatment time 64 weeks), or five times (total treatment time 80 weeks).

[0468] In some embodiments, the maintenance dose for treating RA comprises a dose of 600 mg IMVT-1402 administered subcutaneously once weekly for 16 weeks. In some embodiments, the maintenance dose for treating RA comprises a dose of 600 mg IMVT-1402 administered subcutaneously once weekly for 16 weeks. In some embodiments, the maintenance dose for treating RA comprises a dose of 300 mg IMVT-1402 administered subcutaneously once weekly for 16 weeks. In some embodiments, the maintenance dose for treating RA comprises a dose of 300 mg IMVT-1402 administered subcutaneously once weekly for at least 16 weeks. In some embodiments, the maintenance dose of IMVT-1402 for treating RA is combined with a burst dose for treating RA (e.g., a concurrent or additional dose of IMVT-1402 used to control RA bursts).

[0469] Loading dose

[0470] Loading doses can be added to the administration schedule. While not bound by theory, it is believed that administering a loading dose of anti-FcRn antibody results in a faster reduction in serum IgG and / or autoantibodies, thereby better control of disease symptoms. This is particularly important in diseases with acute symptoms, where additional treatment (e.g., rescue therapy) may be required if IgG and / or antibody reduction is not achieved quickly enough. In many autoimmune diseases, IgG reduction is associated with clinical efficacy.

[0471] Generally, the loading dose is added 1 to 2 weeks before the induction dose. Therefore, in some embodiments, the loading dose is administered on day 4 of the first week of the induction dose. In some embodiments, the loading dose is administered on days 4 and 11 during the two weeks preceding the induction dose. "Day 4," "Day 11," etc., refer to treatment days, where day 1 is the first day of administering the induction dose of the anti-FcRn antibody.

[0472] In some embodiments, the loading dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 100 mg to about 200 mg. In some embodiments, the loading dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, or about 200 mg.

[0473] In some embodiments, the loading dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 200 mg to about 300 mg. In some embodiments, the loading dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, or about 300 mg.

[0474] In some embodiments, the loading dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 300 mg to about 500 mg. In some embodiments, the loading dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, or about 500 mg.

[0475] In some embodiments, the loading dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 500 mg to about 700 mg. In some embodiments, the loading dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) at a dose of about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, or about 700 mg.

[0476] In some embodiments, the loading dose is an anti-FcRn antibody (e.g., batopilimab or IMVT-1402) at a dose of about 700 mg to about 1000 mg. In some embodiments, the loading dose is an anti-FcRn antibody (e.g., battolimab or IMVT-1402) in doses of about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 765 mg, about 770 mg, about 780 mg, about 790 mg, about 800 mg, about 810 mg, about 820 mg, about 830 mg, about 840 mg, about 850 mg, about 860 mg, about 870 mg, about 880 mg, about 890 mg, about 900 mg, about 910 mg, about 920 mg, about 930 mg, about 940 mg, about 950 mg, about 960 mg, about 970 mg, about 980 mg, about 990 mg, or about 1000 mg.

[0477] In some embodiments, the loading dose is an anti-FcRn antibody (e.g., bartolimab or IMVT-1402) at a dose of about 1000 mg to about 1500 mg. In some embodiments, the loading dose is about 1000 mg, about 1010 mg, about 1020 mg, about 1030 mg, about 1040 mg, about 1050 mg, about 1060 mg, about 1070 mg, about 1080 mg, about 1090 mg, about 1100 mg, about 1110 mg, about 1120 mg, about 1130 mg, about 1140 mg, about 1150 mg, about 1160 mg, about 1170 mg, about 1180 mg, about 1190 mg, about 1200 mg, about 1210 mg, about 1220 mg, about 1230 mg, about 1240 mg, about 1250 mg, about 1260 mg, about 1270 mg, about 1280 mg, about 1290 mg, about 1300 mg, about 1310 mg, about 1320 mg, about 1330 mg, or about 1330 mg. Anti-FcRn antibodies (e.g., batopilimab or IMVT-1402) in doses of approximately 1340 mg, 1350 mg, 1360 mg, 1370 mg, 1380 mg, 1390 mg, 1400 mg, 1410 mg, 1420 mg, 1430 mg, 1440 mg, 1450 mg, 1460 mg, 1470 mg, 1480 mg, 1490 mg, or 1500 mg.

[0478] In some embodiments, a loading dose of the anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient via a single (i.e., one) subcutaneous injection. In some embodiments, a loading dose of the anti-FcRn antibody (e.g., battolimab or IMVT-1402) is administered to the patient via two or more consecutive subcutaneous injections (e.g., two consecutive subcutaneous injections).

[0479] In some embodiments, the loading dose is 680 mg of battolimab. In some embodiments, the loading dose is 680 mg of battolimab administered subcutaneously on day 4. In some embodiments, the loading dose is 680 mg of battolimab administered subcutaneously on day 11. In some embodiments, the loading dose is 680 mg of battolimab administered subcutaneously on both days 4 and 11.

[0480] In some embodiments, the loading dose is a 600 mg dose of IMVT-1402. In some embodiments, the loading dose is a 600 mg dose of IMVT-1402 administered subcutaneously. In some embodiments, the loading dose is a 600 mg dose of IMVT-1402 administered subcutaneously on day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14. In some embodiments, the loading dose is a 600 mg dose of IMVT-1402 administered subcutaneously on any two days of day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14. In some embodiments, the loading dose is a 600 mg dose of IMVT-1402 administered subcutaneously on any three days of days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14. In some embodiments, the loading dose is a 600 mg dose of IMVT-1402 administered subcutaneously on day 4. In some embodiments, the loading dose is a 600 mg dose of IMVT-1402 administered subcutaneously on day 11. In some embodiments, the loading dose is a 600 mg dose of IMVT-1402 administered subcutaneously on days 4 and 11.

[0481] In some embodiments, treatment with anti-FcRn antibodies according to the methods described herein results in a reduction of the subject's total IgG level by at least 25% compared to baseline by 7 days after initial administration. In some embodiments, treatment with anti-FcRn antibodies according to the methods described herein res...

Claims

1. A method for treating an autoimmune disease in a subject of need, the method comprising administering to the subject a loading dose of anti-FcRn therapy, as well as an induction dose and a maintenance dose.

2. The method of claim 1, wherein the induction dose is administered for 12 weeks.

3. The method of claim 1, wherein the maintenance dose is administered for 12 weeks.

4. The method of claim 1, wherein the maintenance dose is administered for 12 months.

5. The method of claim 1, wherein the loading dose is administered on day 4 of the first week of the induction dose.

6. The method of claim 1, wherein the loading dose is administered on days 4 and 11 during the first two weeks of administration of the induction dose.

7. The method of claim 1, wherein the induction dose is 680 mg of batolizumab administered subcutaneously once a week.

8. The method of claim 1, wherein the maintenance dose is 340 mg of batolizumab administered subcutaneously once a week.

9. The method of claim 1, wherein the maintenance dose is 340 mg of batolizumab administered subcutaneously once every week.

10. The method of claim 1, wherein the loading dose is a subcutaneous administration of 680 mg of batolizumab.

11. The method of claim 1, wherein the induction dose is 600 mg IMVT-1402 administered subcutaneously once a week.

12. The method of claim 1, wherein the maintenance dose is 300 mg IMVT-1402 administered subcutaneously once weekly.

13. The method of claim 1, wherein the maintenance dose is 300 mg IMVT-1402 administered subcutaneously once every week.

14. The method of claim 1, wherein the loading dose is a subcutaneous administration of 600 mg of IMVT-1402.

15. The method according to claim 1, wherein the autoimmune disease is a progressive autoimmune disease.

16. The method of claim 1, wherein the autoimmune disease is CIDP.

17. The method according to claim 1, wherein the autoimmune disease is myasthenia gravis.

18. A method for treating an autoimmune disease in a subject of need, the method comprising: (a) Administer 680 mg of batolizumab to the subject on day 1; (b) Administer 680 mg of batolizumab to the subject on day 4; (c) Administer 680 mg of batolizumab to the subject on day 8; (d) Administer 680 mg of batolizumab to the subject on day 11; and (e) The subjects were given 680 mg of batolizumab once a week starting on day 15 for a total duration of 12 weeks.

19. The method of claim 18, further comprising step (f): administering 340 mg of batolizumab to the subject once weekly starting from day 85 for a total treatment duration of 24 weeks.

20. The method of claim 18, further comprising the step (g): administering 680 mg of batolizumab to the subject once weekly starting from day 168 for a total treatment duration of 36 weeks.

21. The method of claim 18, comprising subcutaneous administration of the batolizumab.

22. The method of claim 20, wherein the method results in a reduction of at least 50% in the level of at least one autoantibody of the subject compared to baseline up to 7 days after initial administration.

23. The method of claim 18, wherein the method results in a reduction of at least 75% in the level of at least one autoantibody of the subject compared to baseline up to 7 days after initial administration.

24. The method of claim 18, wherein the method results in a reduction of at least 85% in the level of at least one autoantibody of the subject compared to baseline up to 7 days after initial administration.

25. The method according to any one of claims 22 to 24, wherein the autoantibody is an antibody against AChR, MuSK, LRP4, agglutinin, Kv1.4 potassium channel, receptor-linked synaptic protein, cortical actin, acetylcholinesterase, collagen Q, or collagen XIII.

26. The method of claim 18, wherein the method results in a reduction of the subject's total IgG level by at least 50% compared to baseline up to 7 days after initial administration.

27. The method of claim 18, wherein the method results in a reduction of the subject's total IgG level by at least 75% compared to baseline up to 7 days after initial administration.

28. The method of claim 18, wherein the method results in a reduction of the subject's total IgG level by at least 85% compared to baseline up to 7 days after initial administration.

29. The method of claim 18, wherein the autoimmune disease is progressive.

30. The method of claim 18, wherein the autoimmune disease is CIDP.

31. The method of claim 18, wherein the autoimmune disease is myasthenia gravis.

32. A method for treating an autoimmune disease in a subject of need, the method comprising: (a) Administer 600 mg of IMVT-1402 to the subject on day 1; (b) Administer 600 mg of IMVT-1402 to the subject on day 4; (c) Administer 600 mg of IMVT-1402 to the subject on day 8; (d) Administer 600 mg of IMVT-1402 to the subject on day 11; and (e) The subjects were given 600 mg IMVT-1402 once a week starting from day 15 for a total duration of 12 weeks.

33. The method of claim 32, further comprising step (f): administering 300 mg IMVT-1402 to the subject once weekly starting from day 85 for a total treatment duration of 24 weeks.

34. The method of claim 32, further comprising the step (g): administering 600 mg IMVT-1402 to the subject once weekly starting from day 168 for a total treatment duration of 36 weeks.

35. The method of claim 32, comprising subcutaneous administration of the IMVT-1402.

36. The method of claim 33, wherein the method results in a reduction of at least 50% in the level of at least one autoantibody of the subject compared to baseline up to 7 days after initial administration.

37. The method of claim 32, wherein the method results in a reduction of at least 75% in the level of at least one autoantibody of the subject compared to baseline up to 7 days after initial administration.

38. The method of claim 32, wherein the method results in a reduction of at least 85% in the level of at least one autoantibody of the subject compared to baseline up to 7 days after initial administration.

39. The method of claim 32, wherein the method results in a reduction of at least 90% in the level of at least one autoantibody of the subject compared to baseline up to 7 days after initial administration.

40. The method of claim 32, wherein the method results in a reduction of the subject's total IgG level by at least 50% compared to baseline up to 7 days after initial administration.

41. The method of claim 32, wherein the method results in a reduction of the subject's total IgG level by at least 75% compared to baseline up to 7 days after initial administration.

42. The method of claim 32, wherein the method results in a reduction of the subject's total IgG level by at least 85% compared to baseline up to 7 days after initial administration.

43. The method of claim 32, wherein the autoimmune disease is a progressive autoimmune disease.

44. The method of claim 32, wherein the autoimmune disease is CIDP.

45. The method of claim 32, wherein the autoimmune disease is myasthenia gravis.

46. ​​A method for controlling the onset of an autoimmune disease in a subject being treated with anti-FcRn therapy, the method comprising administering at least four doses of an anti-FcRn antibody to the subject.

47. The method of claim 46, comprising administering the anti-FcRn antibody on day 1, day 8, day 15, and day 22.

48. The method of claim 46, comprising administering the anti-FcRn antibody on day 1, day 4, day 8, day 15, and day 22.

49. The method of claim 46, wherein the anti-FcRn antibody is battolizumab.

50. The method of claim 49, wherein the batolizumab is administered subcutaneously.

51. The method of claim 49, comprising administering 680 mg of batolizumab.

52. The method of claim 46, wherein the anti-FcRn antibody is IMVT-1402.

53. The method of claim 52, wherein IMVT-1402 is administered subcutaneously.

54. The method of claim 52, comprising administering 600 mg IMVT-1402.

55. The method of claim 46, wherein the autoimmune disease is a progressive autoimmune disease.

56. The method of claim 46, wherein the autoimmune disease is treated with IVIg.

57. The method of claim 46, wherein the autoimmune disease is being treated with PLEX.

58. The method of claim 46, wherein the autoimmune disease is CIDP.

59. The method of claim 46, wherein the autoimmune disease is myasthenia gravis.

60. A method for treating a subject with Graves' disease (GD), the method comprising administering 550 to 700 mg of an anti-FcRn antibody to the subject once weekly.

61. A method for treating or preventing thyroid eye disease (TED) in a subject with Graves' disease (GD), the method comprising administering 550 to 700 mg of an anti-FcRn antibody to the subject once weekly.

62. A method for inducing remission in a subject suffering from Graves' disease (GD), the method comprising administering 550 to 700 mg of an anti-FcRn antibody to the subject once weekly.

63. The method according to any one of claims 60 to 62, wherein 600 mg of the anti-FcRn antibody is administered to the subject once a week.

64. The method according to any one of claims 60 to 63, wherein the antibody is administered to the subject for a period of 20 to 60 weeks.

65. The method according to any one of claims 60 to 64, wherein the antibody is administered to the subject for 52 weeks.

66. The method according to any one of claims 60 to 64, wherein the antibody is administered to the subject for 26 weeks.

67. The method of claim 66, wherein the antibody is administered to the subject at a reduced dose after the initial 26 weeks.

68. The method of claim 67, wherein the reduced dose of the antibody is administered to the subject once weekly.

69. The method of claim 68, wherein the subject is given 300 mg of the reduced dose of the antibody once a week for 26 weeks.

70. The method according to any one of claims 60 to 69, wherein the anti-FcRn antibody is IMVT-1402.

71. The method according to any one of claims 60 to 70, wherein the antibody comprises: a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region (HCDR) 1 containing the amino acid sequence of SEQ ID NO: 7, an HCDR2 containing the amino acid sequence of SEQ ID NO: 8, and an HCDR3 containing the amino acid sequence of SEQ ID NO: 9; and a light chain variable region comprising a light chain complementarity-determining region (LCDR) 1 containing the amino acid sequence of SEQ ID NO: 10, an LCDR2 containing the amino acid sequence of SEQ ID NO: 11, and an LCDR3 containing the amino acid sequence of SEQ ID NO:

12.

72. The method according to any one of claims 60 to 71, wherein the antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 15 and VL comprising the amino acid sequence of SEQ ID NO:

16.

73. The method according to any one of claims 60 to 72, wherein the antibody comprises: a heavy chain comprising the amino acid sequence of SEQ ID NO: 19 and a light chain comprising the amino acid sequence of SEQ ID NO:

20.

74. The method according to any one of claims 60 to 72, wherein the antibody comprises: a heavy chain comprising the amino acid sequence of SEQ ID NO: 21 and a light chain comprising the amino acid sequence of SEQ ID NO:

22.

75. The method according to any one of claims 60 to 74, wherein the subject suffered from significant hyperthyroidism prior to the administration.

76. The method of claim 75, wherein the subject's baseline triiodothyronine (T3) level is above the upper limit of normal (ULN).

77. The method of claim 75 or 76, wherein the baseline free thyroxine (FT4) level of the subject is higher than that of ULN.

78. The method according to any one of claims 75 to 77, wherein the baseline TSH level of the subject does not exceed the lower limit of normal (LLN).

79. The method according to any one of claims 60 to 74, wherein the subject suffered from subclinical hyperthyroidism prior to the administration.

80. The method of claim 79, wherein the subject's T3 level is within the clinically normal T3 level.

81. The method of claim 79 or 80, wherein the subject's FT4 level is within the clinically normal range.

82. The method according to any one of claims 79 to 81, wherein the subject has a thyroid-stimulating hormone (TSH) level of less than 0.1 mU / L.

83. The method according to any one of claims 60 to 82, wherein the subject is receiving an antithyroid drug (ATD) at the time of administration of the anti-FcRn antibody.

84. The method of claim 83, wherein the subject had previously received an antithyroid drug (ATD) for at least 3 months prior to administration of the anti-FcRn antibody.

85. The method according to claim 83 or 84, wherein the ATD is methimazole, carbimazole, or propylthiouracil.

86. The method according to any one of claims 83 to 85, wherein the subject is receiving an ATD dose of at least 20 mg / day of methimazole prior to administration of the anti-FcRn antibody.

87. The method according to any one of claims 83 to 86, wherein the subject is receiving an ATD dose of at least 30 mg / day of carbimazole prior to administration of the anti-FcRn antibody.

88. The method according to any one of claims 83 to 87, wherein the subject is receiving an ATD dose of at least 200 mg / day of propylthiouracil prior to administration of the anti-FcRn antibody.

89. The method of any one of claims 83 to 88, wherein the subject continues to receive the ATD for four weeks prior to baseline assessment of the anti-FcRn antibody.

90. The method of any one of claims 83 to 88, wherein the subject has been receiving an antithyroid drug (ATD) for at least six months prior to baseline assessment.

91. The method according to claim 90, wherein the ATD is methimazole, carbimazole, or propylthiouracil.

92. The method according to any one of claims 83, 90 or 91, wherein the subject is receiving an ATD dose of at least 15 mg / day of methimazole prior to administration of the anti-FcRn antibody.

93. The method according to any one of claims 83 to 85, wherein the subject is receiving an ATD dose of at least 20 mg / day of carbimazole prior to administration of the anti-FcRn antibody.

94. The method according to any one of claims 83 to 85, wherein the subject is receiving an ATD dose of at least 150 mg / day of propylthiouracil prior to administration of the anti-FcRn antibody.

95. The method of claim 94, wherein the object simultaneously accepts an ATD.

96. The method of claim 95, wherein the subject receives ATD at a dose of at least 10 mg / day of methimazole.

97. The method of claim 95, wherein the subject receives an ATD at a dose of at least 15 mg / day of carbimazole.

98. The method of claim 95, wherein the subject receives ATD at a dose of at least 100 mg / day of propylthiouracil.

99. The method according to any one of claims 60 to 98, wherein the subject does not have or has not previously had hyperthyroidism not caused by GD.

100. The method of claim 99, wherein the subject does not suffer from toxic adenoma or toxic multinodular goiter.

101. The method of claim 99 or 100, wherein the subject does not have a history of thyroid storm within six months prior to administration of the anti-FcRn antibody.

102. The method according to any one of claims 60 to 101, wherein the subject does not suffer from TED.

103. The method according to any one of claims 60 to 102, wherein the subject does not suffer from moderate to severe active TED requiring immediate surgical intervention, corrective surgery, irradiation and / or medical treatment.

104. The method according to any one of claims 60 to 103, wherein the subject does not have a history of non-compliance with ATD therapy.

105. The method according to any one of claims 60 to 104, wherein the anti-FcRn antibody is administered subcutaneously.

106. The method according to any one of claims 60 to 105, wherein the administration of the anti-FcRn antibody at or before week 25 induces normal thyroid function in the subject.

107. The method of claim 106, wherein the application reduces the T3 level of the object to a normal range.

108. The method of claim 106 or 107, wherein the application reduces the FT4 level of the object to a normal range.

109. The method according to any one of claims 106 to 108, wherein the application raises the subject's TSH level to within the normal range.

110. The method according to any one of claims 60 to 109, wherein the subject stops receiving ATD at or before the 26th week of administration.

111. The method according to any one of claims 60 to 110, wherein administration of the anti-FcRn antibody induces normal thyroid function in the subject at or before week 52 of administration.

112. The method of claim 111, wherein administering the anti-FcRn antibody reduces the subject's T3 level to within the normal range.

113. The method of claim 111 or 112, wherein administration of the anti-FcRn antibody reduces the subject's FT4 level to the normal range.

114. The method according to any one of claims 111 to 113, wherein administration of the anti-FcRn antibody increases the subject's TSH level to within the normal range.

115. The method according to any one of claims 111 to 114, wherein the subject discontinues ATD at or before the administration of the anti-FcRn antibody at week 52.

116. The method according to any one of claims 60 to 115, wherein administering the anti-FcRn antibody prevents the subject from having one or more of the following ocular symptoms or improves one or more of the following ocular symptoms in the subject: bulging eyes; gritty feeling in the eyes; eye pressure or pain; eyelid retraction; red or inflamed eyes; photosensitivity; blurred or diplopia, or vision loss.

117. The method according to any one of claims 60 to 116, wherein administration of the anti-FcRn antibody induces remission in the subject (i.e., the subject is thyroid-normal for at least 6 months or longer after discontinuation of both therapies).

118. A method for treating a subject with rheumatoid arthritis (RA), the method comprising administering 550 to 700 mg of an anti-FcRn antibody to the subject once weekly.

119. The method of claim 118, wherein 600 mg of the anti-FcRn antibody is administered to the subject once weekly.

120. The method of claim 118 or 119, wherein 600 mg of the anti-FcRn antibody is administered to the subject weekly for at least 16 weeks, subsequently (i) Administer 600 mg of the anti-FcRn antibody to the subject once a week; or (ii) Administer 300 mg of the anti-FcRn antibody to the subject once a week.

121. The method according to any one of claims 118 to 120, wherein the anti-FcRn antibody is administered subcutaneously.

122. The method according to any one of claims 118 to 121, wherein the subject suffers from active RA.

123. The method according to any one of claims 118 to 122, wherein the subject suffers from refractory RA.

124. The method according to any one of claims 118 to 123, wherein the subject has moderate disease activity.

125. The method according to any one of claims 118 to 124, wherein the DAS28-ESR score of the object is greater than 3.

2.

126. The method according to any one of claims 118 to 125, wherein the CDAI score of the object is greater than 10.

127. The method according to any one of claims 118 to 126, wherein the subject has one or more symptoms suggesting an active disease.

128. The method according to any one of claims 118 to 127, wherein the subject cannot gradually reduce glucocorticoid treatment to less than 7.5 mg / day.

129. The method according to any one of claims 118 to 128, wherein the subject shows rapid radiographic progress of RA, indicated by a change of ≥5 points in the van der Heide modified Sharp score over 1 year.

130. The method according to any one of claims 118 to 129, wherein the subject is positive for rheumatoid factor (RF).

131. The method of claim 130, wherein the RA synovial fluid of the subject is positive for IgG or IgA RF.

132. The method of claim 130 or 131, wherein the RF level of the object is higher than 25 U / ml.

133. The method according to any one of claims 130 to 132, wherein the RF level of the object is higher than 100 U / ml.

134. The method according to any one of claims 118 to 133, wherein the subject is positive for anti-citrullinated protein autoantibody (ACPA).

135. The method according to any one of claims 118 to 134, wherein the object has at least 6 / 68 tender and / or painful joints (TJC) at baseline.

136. The method of any one of claims 118 to 135, wherein the object has at least a 6 / 66 swollen joint (SJC) at baseline.

137. The method according to any one of claims 118 to 136, wherein the baseline level of circulating C-reactive protein (CRP) of said subject is at least 1.5 × ULN.

138. The method of any one of claims 118 to 137, wherein the subject has a baseline disease activity score 28 (DAS28-CRP) greater than 4.1 as determined using C-reactive protein.

139. The method according to any one of claims 118 to 138, wherein the object is not responsive to two or three classes of biological (b) or targeted synthetic (ts) disease-modified antirheumatic drugs (b / tsDMARDs).

140. The method of claim 139, wherein the subject has been treated with a biological TNF-α inhibitor (e.g., infliximab, sertozumab, golimumab, etanercept, adalimumab).

141. The method according to any one of claims 118 to 139, wherein the subject has been treated with a JAK inhibitor.

142. The method according to any one of claims 119 to 139, wherein the subject has been treated with a bDMARD other than a TNF-α inhibitor.

143. The method according to any one of claims 118 to 142, wherein the object responds to rituximab.

144. The method according to any one of claims 118 to 143, wherein the subject is treated with at least one known (c) DMARD (e.g., MTX, hydroxychloroquine, sulfasalazine).

145. The method according to any one of claims 118 to 144, wherein the subject does not receive glucocorticoids at a dose >10 mg / day.

146. The method of any one of claims 118 to 145, wherein the subject has not received three or more joint injections within six weeks prior to baseline assessment.

147. The method of any one of claims 118 to 146, wherein the subject has not received systemic glucocorticoids administered via intramuscular or intravenous (IV) injection within six weeks prior to baseline assessment.

148. The method according to any one of claims 118 to 147, wherein the application reduces the RF level of the object.

149. The method according to any one of claims 118 to 148, wherein the application reduces the ACAP of the object.

150. The method according to any one of claims 118 to 149, wherein the subject achieves an ACR20 response at week 14, week 16, or week 32 of administration.

151. The method of claim 150, wherein the object shows at least a 20% improvement over the baseline in TJC68.

152. The method of claim 150 or 151, wherein the object shows at least a 20% improvement in SJC66 relative to the baseline.

153. The method according to any one of claims 150 to 152, wherein the object is improved by at least 20% relative to the baseline in at least three of the following parameters: (i) Physician Global Disease Activity Assessment (PhGA); (ii) Patient overall disease activity assessment (PtGA); (iii) Patient pain assessment (100 mm VAS); (iv) Health Assessment Questionnaire - Disability Index (HAQ-DI); and (v) High-sensitivity C-reactive protein (hsCRP).

154. The method according to any one of claims 118 to 153, wherein the subject achieves an ACR20 response at week 14 or week 16 of administration and has a CDAI score change from week 16 to week 32 of administration.

155. The method according to any one of claims 118 to 154, wherein the subject achieves an ACR20 response at week 14 or week 16 of administration and has a change in SDAI score from week 16 to week 32 of administration.

156. The method according to any one of claims 118 to 155, wherein the anti-FcRn antibody is IMVT-1402.

157. The method according to any one of claims 118 to 156, wherein the antibody comprises: a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region (HCDR) 1 containing the amino acid sequence of SEQ ID NO: 7, an HCDR2 containing the amino acid sequence of SEQ ID NO: 8, and an HCDR3 containing the amino acid sequence of SEQ ID NO: 9; and a light chain variable region comprising a light chain complementarity-determining region (LCDR) 1 containing the amino acid sequence of SEQ ID NO: 10, an LCDR2 containing the amino acid sequence of SEQ ID NO: 11, and an LCDR3 containing the amino acid sequence of SEQ ID NO:

12.

158. The method according to any one of claims 118 to 157, wherein the antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 15 and VL comprising the amino acid sequence of SEQ ID NO:

16.

159. The method according to any one of claims 118 to 158, wherein the antibody comprises: a heavy chain comprising the amino acid sequence of SEQ ID NO: 19 and a light chain comprising the amino acid sequence of SEQ ID NO:

20.

160. The method according to any one of claims 118 to 159, wherein the antibody comprises: a heavy chain comprising the amino acid sequence of SEQ ID NO: 21 and a light chain comprising the amino acid sequence of SEQ ID NO:

22.

161. A method for treating Graves' disease (GD) in a subject receiving an antithyroid drug (ATD) at a single dose, the method comprising: (i) Administer anti-FcRn antibody to the subject at a dose in the range of 580 to 700 mg; (ii) Measure the T3 and T4 levels of the subject; (iii) If the T3 and / or T4 levels are below the ULN, reduce the dose of the ATD or stop the ATD; (iii) Reducing the dose of the anti-FcRn antibody to a dose in the range of 280 to 400 mg / dose; and (iv) Increase the dose of the ATD or restart the subject from receiving the ATD to maintain T3 and T4 levels below ULN.

162. A method for treating Graves' disease (GD) in a subject receiving an antithyroid drug (ATD) at a single dose, the method comprising: (i) Administer anti-FcRn antibody to the subject at a dose in the range of 580 to 700 mg; (ii) Measure the T3 and T4 levels of the subject; (iii) If the T3 and / or T4 levels are below the ULN, reduce the dose of the ATD or discontinue the ATD; and (iii) Maintain the dose of the anti-FcRn antibody while administering a low dose of ATD or no ATD to the subject to maintain T3 and T4 levels below ULN.

163. A method for treating Graves' disease (GD) in a subject receiving an antithyroid drug (ATD) at a single dose, the method comprising: (i) Administering anti-FcRn antibody to the subject; (ii) Measure the T3 and T4 levels of the subject; (iii) If the T3 and / or T4 levels are below the ULN, reduce the dose of the ATD or stop the ATD; (iii) Reduce the dose of the anti-FcRn antibody; and (iv) Increase the dose of the ATD or restart the subject from receiving the ATD to maintain T3 and T4 levels below ULN.

164. A method for treating Graves' disease (GD) in a subject receiving an antithyroid drug (ATD) at a single dose, the method comprising: (i) Administer an anti-FcRn antibody to the subject at a dose; (ii) Measure the T3 and T4 levels of the subject; (iii) If the T3 and / or T4 levels are below the ULN, reduce the dose of the ATD or discontinue the ATD; and (iii) Maintain the dose of the anti-FcRn antibody while administering a low dose of ATD or no ATD to the subject to maintain T3 and T4 levels below ULN.

165. A method for treating a subject with myasthenia gravis (MG), the method comprising administering 550 to 700 mg of an anti-FcRn antibody to the subject once weekly.

166. A method for inducing remission in a subject suffering from myasthenia gravis (MG), the method comprising administering 550 to 700 mg of an anti-FcRn antibody to the subject once weekly.

167. The method of claim 165 or 166, wherein 600 mg of the anti-FcRn antibody is administered to the subject once weekly.

168. The method according to any one of claims 165 to 167, wherein the application of the antibody to the subject lasts for a period of 20 to 60 weeks.

169. The method according to any one of claims 165 to 168, wherein the antibody is administered to the subject for 52 weeks.

170. The method according to any one of claims 165 to 168, wherein the antibody is administered to the subject for 26 weeks.

171. The method of claim 170, wherein the antibody is administered to the subject at a reduced dose after 26 weeks.

172. The method of claim 171, wherein 300 mg of the antibody is administered to the subject once a week.

173. The method of claim 171 or 172, wherein 300 mg of the antibody is administered to the subject once a week for 26 weeks.

174. The method of claim 171 or 172, wherein 300 mg of the antibody is administered to the subject once a week indefinitely.

175. The method according to any one of claims 165 to 174, wherein the anti-FcRn antibody is IMVT-1402.

176. The method according to any one of claims 165 to 175, wherein the antibody comprises: a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region (HCDR) 1 containing the amino acid sequence of SEQ ID NO: 7, an HCDR2 containing the amino acid sequence of SEQ ID NO: 8, and an HCDR3 containing the amino acid sequence of SEQ ID NO: 9; and a light chain variable region comprising a light chain complementarity-determining region (LCDR) 1 containing the amino acid sequence of SEQ ID NO: 10, an LCDR2 containing the amino acid sequence of SEQ ID NO: 11, and an LCDR3 containing the amino acid sequence of SEQ ID NO:

12.

177. The method according to any one of claims 165 to 176, wherein the antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 15 and VL comprising the amino acid sequence of SEQ ID NO:

16.

178. The method according to any one of claims 165 to 177, wherein the antibody comprises: a heavy chain comprising the amino acid sequence of SEQ ID NO: 19 and a light chain comprising the amino acid sequence of SEQ ID NO:

20.

179. The method according to any one of claims 165 to 177, wherein the antibody comprises: a heavy chain comprising the amino acid sequence of SEQ ID NO: 21 and a light chain comprising the amino acid sequence of SEQ ID NO:

22.

180. The method according to any one of claims 165 to 179, wherein the subject is positive for anti-acetylcholine receptor (AChR) autoantibodies (anti-AChR+).

181. The method according to any one of claims 165 to 180, wherein the subject is positive for an anti-muscle-specific kinase (MuSK) autoantibody (anti-MuSK+).

182. The method according to any one of claims 165 to 181, wherein the subject is positive for anti-lipoprotein receptor-associated protein 4 (LRP4) autoantibody (anti-LRP4+).

183. The method according to any one of claims 165 to 182, wherein the administration reduces the level of anti-AChR autoantibodies in the serum of the subject relative to the level of anti-AChR autoantibodies in the serum prior to the administration.

184. The method according to any one of claims 165 to 183, wherein the administration reduces the level of anti-MuSK autoantibodies in the serum of the subject relative to the level of anti-MuSK autoantibodies in the serum prior to the administration.

185. The method according to any one of claims 165 to 184, wherein the administration causes a reduction in the level of anti-LRP4 autoantibodies in the serum of the subject relative to the level of anti-LRP4 autoantibodies in the serum prior to the administration.

186. The method according to any one of claims 165 to 185, wherein the application prevents the subject from having one or more of the following symptoms or improves one or more of the following symptoms of the subject: weakness of some or all muscles of the body, blurred vision, slurred speech, weakness of the arms, falls, unsteady gait, dysphagia, chronic fatigue and / or dyspnea.

187. A method for treating a subject with chronic inflammatory demyelinating polyneuropathy (CIDP), the method comprising administering 200 to 400 mg of an anti-FcRn antibody to the subject once weekly.

188. A method for treating a subject with chronic inflammatory demyelinating polyneuropathy (CIDP), the method comprising administering 550 to 700 mg of an anti-FcRn antibody to the subject once weekly.

189. The method of claim 187 or 188, wherein the anti-FcRn antibody is administered to the subject for 20 to 60 weeks.

190. The method according to any one of claims 187 to 189, wherein the anti-FcRn antibody is administered to the subject for 24 weeks.

191. The method according to any one of claims 187 to 190, wherein the method further comprises administering a loaded dose of the anti-FcRn antibody to the subject on days 3 to 5 of the first week of administration.

192. The method of claim 191, wherein the anti-FcRn antibody loading dose is administered to the subject on day 4 of the first week of administration.

193. The method of claim 191 or 192, wherein the loading dose of the anti-FcRn antibody is the same as the weekly dose of the anti-FcRn antibody.

194. The method according to any one of claims 191 to 193, wherein the loading dose of the anti-FcRn antibody is 600 mg.

195. The method according to any one of claims 191 to 194, wherein the administration of the anti-FcRn antibody to the subject is continued for an additional 52 weeks.

196. The method of claim 195, wherein 600 mg of the anti-FcRn antibody is administered to the subject once weekly.

197. The method of claim 196, wherein 300 mg of the anti-FcRn antibody is administered to the subject once a week.

198. The method according to claims 195 to 197, wherein the method further comprises administering a loaded dose of the anti-FcRn antibody to the subject on days 3 to 5 of the first week of the additional 52 weeks.

199. The method of claim 198, wherein the anti-FcRn antibody loading dose is administered to the subject on day 4 of the first week of the additional 52 weeks.

200. The method of claim 198 or 199, wherein the loading dose of the anti-FcRn antibody is the same as the weekly dose of the anti-FcRn antibody.

201. The method according to any one of claims 190 to 200, wherein the loading dose of the anti-FcRn antibody is 600 mg.

202. The method according to any one of claims 187 to 201, wherein the subject suffers from typical CIDP.

203. The method according to any one of claims 187 to 202, wherein the object suffers from a CIDP variant.

204. The method of claim 203, wherein the CIDP variant is a multifocal CIDP.

205. The method of claim 203, wherein the CIDP variant is a motion CIDP.

206. The method according to any one of claims 200 to 205, wherein the subject does not suffer from sensory CIDP.

207. The method according to any one of claims 200 to 206, wherein the object does not suffer from remote CIDP.

208. The method according to any one of claims 187 to 207, wherein the subject is receiving or has received first-line therapy with CIDP.

209. The method of claim 208, wherein the first-line therapy for CIDP is a corticosteroid.

210. The method of claim 209, wherein the subject is receiving corticosteroids orally daily or every other day.

211. The method of claim 211, wherein the subject is receiving corticosteroids via a pulse protocol.

212. The method according to any one of claims 209 to 211, wherein the subject gradually reduces corticosteroids while receiving the anti-FcRn antibody.

213. The method according to any one of claims 209 to 212, wherein the subject discontinues corticosteroids before receiving the anti-FcRn antibody.

214. The method of any one of claims 208, wherein the first-line therapy for CIDP is immunoglobulin (Ig) therapy.

215. The method of claim 214, wherein the Ig therapy is an intravenous Ig infusion (IVIg).

216. The method of claim 215, wherein the Ig therapy is a subcutaneous Ig infusion (SCIg).

217. The method according to any one of claims 214 to 216, wherein the subject discontinues Ig therapy prior to receiving the anti-FcRn antibody.

218. The method of claim 208, wherein the first-line therapy for CIDP is plasma exchange (PLEX).

219. The method of claim 218, wherein the subject undergoes discontinuous PLEX treatment prior to receiving the anti-FcRn antibody.

220. The method of any one of claims 212, 217 or 219, wherein the subject relapsed during a 24-week administration period, as measured by an adjusted inflammatory neuropathy cause and treatment (aINCAT) score.

221. The method of any one of claims 212, 217 or 219, wherein the subject did not relapse during the 24-week administration period, as measured by an aINCAT score.

222. The method according to any one of claims 187 to 221, wherein applying the anti-FcRn antibody results in an increase in average grip strength relative to before the application.

223. The method according to any one of claims 187 to 222, wherein administration of the anti-FcRn antibody results in an improvement in the Inflammatory Roschön Total Loss of Energy Scale (I-RODS) score relative to the period prior to administration.

224. The method according to any one of claims 187 to 223, wherein the administration of the anti-FcRn antibody results in an increase in the MCR-SS score relative to the period prior to the administration.

225. The method according to any one of claims 187 to 224, wherein the administration of the anti-FcRn antibody results in a decrease in the timed stand-up walk (TUG) test score relative to before the administration.

226. The method according to any one of claims 187 to 225, wherein the administration of the anti-FcRn antibody results in a reduction of total IgG relative to the state prior to the administration.

227. The method according to any one of claims 187 to 226, wherein the administration of the anti-FcRn antibody results in a reduction of the IgG subclass relative to the state prior to the administration.

228. The method according to any one of claims 187 to 227, wherein the administration of the anti-FcRn antibody reduces the number of autoantibodies targeting myelin relative to the level prior to the administration.

229. The method according to any one of claims 187 to 228, wherein the administration of the anti-FcRn antibody results in a reduction of the immune complex (IC) relative to the state prior to the administration.

230. The method according to any one of claims 187 to 229, wherein the administration of the anti-FcRn antibody results in a reduction of the neurocilia light chain (NfL) relative to the state prior to the administration.

231. The method according to any one of claims 187 to 229, wherein the anti-FcRn antibody is IMVT-1402.

232. The method according to any one of claims 187 to 231, wherein the antibody comprises: a heavy chain variable region (VH) comprising a heavy chain complementarity-determining region (HCDR) 1 containing the amino acid sequence of SEQ ID NO: 7, an HCDR2 containing the amino acid sequence of SEQ ID NO: 8, and an HCDR3 containing the amino acid sequence of SEQ ID NO: 9; and a light chain variable region comprising a light chain complementarity-determining region (LCDR) 1 containing the amino acid sequence of SEQ ID NO: 10, an LCDR2 containing the amino acid sequence of SEQ ID NO: 11, and an LCDR3 containing the amino acid sequence of SEQ ID NO:

12.

233. The method according to any one of claims 187 to 232, wherein the antibody comprises: VH comprising the amino acid sequence of SEQ ID NO: 15 and VL comprising the amino acid sequence of SEQ ID NO:

16.

234. The method according to any one of claims 187 to 233, wherein the antibody comprises: a heavy chain comprising the amino acid sequence of SEQ ID NO: 19 and a light chain comprising the amino acid sequence of SEQ ID NO:

20.

235. The method according to any one of claims 187 to 233, wherein the antibody comprises: a heavy chain comprising the amino acid sequence of SEQ ID NO: 21 and a light chain comprising the amino acid sequence of SEQ ID NO: 22.

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