Dosage regimen for treating multifocal motor neuropathy (MMN)

Abstract

Provided are a method and a dosing regimen for treating multifocal motor neuropathy (MMN) using an antibody that specifically binds to the C2b portion of complement component 2 (C2).

Description

Background Art

[0001] (Background) Multifocal motor neuropathy (MMN) is a rare chronic immune-mediated neuropathy mainly associated with progressive muscle weakness in the hands, forearms, and lower legs. It is clinically characterized by progressive asymmetric weakness affecting two or more nerves and partial motor conduction block. The estimated prevalence of MMN is 0.6 - 2 per 100,000 people and typically presents as a pure motor neuropathy of the asymmetric upper limbs. Unlike amyotrophic lateral sclerosis (ALS) which affects both the upper and lower motor neuron pathways, MMN affects only the lower motor neuron pathway, specifically the peripheral nerves originating from the lower motor neurons. The characteristic of this disease is the presence of multifocal motor conduction blocks, i.e., propagation disorders of action potentials along axons, and patients often show high serum levels of immunoglobulin M (IgM) antibodies against ganglioside GM1 (monosialotetrahexosyl-ganglioside). GM1 is widely expressed in the nervous system, particularly by neurons and Schwann cells around the nodes of Ranvier. The current general view is that GM1 antibodies target the axonal sheath of the nodes of Ranvier. This is thought to interfere with the interaction between axons and Schwann cells, causing nodule enlargement and direct damage to axons.

[0002] The presence and titer of IgM anti-ganglioside GM1 (anti-GM1) antibodies (observed in about 40% of MMN patients) and their complement activation properties correlate with clinical features such as weakness and axonal damage. The binding of these anti-GM1 antibodies to GM1 results in the activation of the classical complement pathway and subsequent membrane attack complex (MAC) deposition. Consequently, this MAC deposition causes disruption of the Schwann cell - axonal sheath junction, displacement of ion channel clustering, and demyelination, leading to disturbance of membrane integrity in the (para)nodal region. These findings suggest that complement plays an important role in the pathogenesis of MMN and that inhibition of complement activation may provide a new treatment option for this disease.

[0003] Currently, high-dose intravenous immunoglobulin (IVIg) therapy is the only approved treatment for MMN. IVIg therapy often improves muscle strength, but the efficacy of IVIg in reducing MMN symptoms declines after several years, and many patients report progressive neurological deficits. Despite treatment with IVIg, MMN-related disorders continue to progress because axonal degeneration persists.

[0004] Accordingly, unmet medical needs for effective treatment options targeting MMN still exist. SUMMARY OF THE INVENTION

[0005] (Summary) The present disclosure is directed to methods of treating MMN with a complement component 2 (C2) inhibitor. Also provided herein is a specific dosing regimen for administering a C2 inhibitor that results in a rapid decrease in free C2 levels in the blood of a subject having MMN. In certain embodiments, the dosing regimen includes a loading regimen that rapidly decreases free C2 in the subject and a maintenance regimen that maintains the subject's decreased free C2 levels thereafter.

[0006] In one aspect, provided herein is a method of treating multifocal motor neuropathy (MMN) in a subject in need thereof, the method comprising administering to the subject an effective amount of a C2 inhibitor.

[0007] In certain embodiments, the C2 inhibitor is administered at a dose of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of 10 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of 5 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of 10 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of 15 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of 30 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of 60 mg / kg.

[0008] In certain embodiments, the C2 inhibitor is administered at a fixed dose of 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered at a fixed dose of 1200 mg.

[0009] In certain embodiments, the C2 inhibitor is administered intravenously or subcutaneously. In certain embodiments, the C2 inhibitor is administered intravenously. In certain embodiments, the C2 inhibitor is administered subcutaneously.

[0010] In certain embodiments, the C2 inhibitor is administered once a week. In certain embodiments, the C2 inhibitor is administered once every two weeks. In certain embodiments, the C2 inhibitor is administered once every four weeks. In certain embodiments, the C2 inhibitor is administered once every eight weeks.

[0011] In certain embodiments, the C2 inhibitor is administered intravenously at a dose of 10 mg / kg once a week or once every two weeks. In certain embodiments, the C2 inhibitor is administered intravenously at a dose of 30 mg / kg once a week or once every two weeks. In certain embodiments, the C2 inhibitor is administered intravenously at a dose of 60 mg / kg once a week or once every two weeks. In certain embodiments, the C2 inhibitor is administered at a dose of 15 mg / kg once a week or once every two weeks. In certain embodiments, the C2 inhibitor is administered at a dose of 5 mg / kg once a week, once every two weeks, or once every four weeks.

[0012] In certain embodiments, the C2 inhibitor is administered according to a loading regimen that reduces the level of free C2 in the subject's blood to or below a threshold level.

[0013] In certain embodiments, the method further comprises a maintenance regimen after the loading regimen, wherein the maintenance regimen comprises administration of the C2 inhibitor by a regimen that maintains the level of free C2 in the subject's blood at or below the threshold level.

[0014] In certain embodiments, the threshold level is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, or 0.8 μg / mL. In certain embodiments, the threshold level is 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20% of the baseline level of free C2 in the subject.

[0015] In certain embodiments, the loading regimen is a single initial dose followed by one or more subsequent doses. In certain embodiments, each of the one or more subsequent doses is an amount lower than the single initial dose.

[0016] In certain embodiments, following the single initial dose, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 subsequent doses follow. In certain embodiments, the subsequent doses are administered once a week, once every two weeks, or once every four weeks.

[0017] In certain embodiments, there are four subsequent doses after a single initial dose, where the subsequent doses are administered once a week. In certain embodiments, the first subsequent dose is administered one week after the single initial dose.

[0018] In certain embodiments, the single initial dose is from 0.1 mg / kg to 100 mg / kg. In certain embodiments, the single initial dose is from 10 mg / kg to 60 mg / kg. In certain embodiments, the single initial dose is 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the single initial dose is 15 mg / kg. In certain embodiments, the single initial dose is 30 mg / kg. In certain embodiments, the single initial dose is 60 mg / kg.

[0019] In certain embodiments, the single initial dose is a fixed dose of 500 mg to 1500 mg. In certain embodiments, the single initial dose is a fixed dose of 1200 mg.

[0020] In certain embodiments, the subsequent doses are each from 0.1 mg / kg to 100 mg / kg. In certain embodiments, the subsequent doses are each from 5 mg / kg to 60 mg / kg. In certain embodiments, the subsequent doses are each 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the subsequent doses are each 5 mg / kg. In certain embodiments, the subsequent doses are each 10 mg / kg. In certain embodiments, the subsequent doses are each 30 mg / kg.

[0021] In certain embodiments, the subsequent doses are each a fixed dose of 500 mg to 1500 mg. In certain embodiments, the subsequent doses are each a fixed dose of 1200 mg.

[0022] In certain embodiments, a single initial dose is 15 mg / kg and subsequent doses are each 5 mg / kg. In certain embodiments, a single initial dose is 30 mg / kg and subsequent doses are each 10 mg / kg. In certain embodiments, a single initial dose is 60 mg / kg and subsequent doses are each 30 mg / kg.

[0023] In certain embodiments, the loading regimen is administered intravenously or subcutaneously. In certain embodiments, the loading regimen is administered intravenously. In certain embodiments, the loading regimen is administered subcutaneously.

[0024] In certain embodiments, the loading regimen reduces the level of free C2 to or below the threshold level in 1, 2, 3, 4, 5, 6, or 7 days. In certain embodiments, the loading regimen reduces the level of free C2 to or below the threshold level in 1, 2, 3, 4, or 5 weeks.

[0025] In certain embodiments, the maintenance regimen is a dose of 0.1 - 100 mg / kg administered once every 1, 2, 3, 4, 5, 6, or 8 weeks.

[0026] In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once a week. In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every two weeks. In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every three weeks. In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every four weeks. In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every five weeks. In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every six weeks. In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every seven weeks. In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every eight weeks.

[0027] In certain embodiments, the maintenance regimen is a dose of 500 mg to 1500 mg administered once every 1, 2, 3, 4, 5, 6, 7, or 8 weeks. In certain embodiments, subsequent doses are each a fixed dose of 1200 mg.

[0028] In certain embodiments, the maintenance regimen is administered 1, 2, 3, 4, 5, 6, 7, or 8 weeks after the loading regimen. In certain embodiments, the maintenance regimen is administered when the level of free C2 in the subject's blood exceeds a threshold level. In certain embodiments, the maintenance regimen is administered intravenously or subcutaneously. In certain embodiments, the maintenance regimen is administered intravenously. In certain embodiments, the maintenance regimen is administered subcutaneously.

[0029] In certain embodiments, the loading regimen is a single initial dose of 30 mg / kg; and four subsequent doses of 10 mg / kg each, administered once a week starting 1 week after the single initial dose; and the maintenance regimen is a dose of 10 mg / kg administered once every 2 weeks.

[0030] In certain embodiments, the loading regimen is a single initial dose of 60 mg / kg; and four subsequent doses of 30 mg / kg each, administered once a week starting 1 week after the single initial dose; and the maintenance regimen is a dose of 30 mg / kg administered once every 2 weeks.

[0031] In certain embodiments, the loading regimen is a single initial dose of 15 mg / kg; and four subsequent doses of 5 mg / kg each, administered once a week starting 1 week after the single initial dose; and the maintenance regimen is a dose of 5 mg / kg administered once every 4 weeks.

[0032] In certain embodiments, the maintenance regimen begins 1 week after the last subsequent dose of the loading regimen. In certain embodiments, the maintenance regimen begins 2 weeks after the last subsequent dose of the loading regimen.

[0033] In certain embodiments, the loading regimen is administered intravenously and the maintenance regimen is administered subcutaneously. In certain embodiments, the loading regimen is administered subcutaneously and the maintenance regimen is administered intravenously. In certain embodiments, both the loading regimen and the maintenance regimen are administered intravenously. In certain embodiments, both the loading regimen and the maintenance regimen are administered subcutaneously.

[0034] In certain embodiments, the subject's motor strength and / or the subject's sensory symptoms are improved compared to the subject's motor strength and / or the subject's sensory symptoms achieved with standard treatment using intravenous immunoglobulin (IVIg).

[0035] In certain embodiments, the subject exhibits a decrease in the level of free C2 in the subject's blood after administration of a C2 inhibitor compared to the baseline level of free C2 in the subject's blood. In certain embodiments, the level of free C2 in the subject's blood is decreased by at least about 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% compared to the baseline level of free C2 in the subject's blood.

[0036] In certain embodiments, the method further comprises administering an additional therapeutic agent to the subject. In certain embodiments, the additional therapeutic agent is IVIg. In certain embodiments, the additional therapeutic agent is rituximab, eculizumab, cyclophosphamide, or mycophenolate mofetil.

[0037] In certain embodiments, IVIg is administered to the subject once every two weeks, once every three weeks, once every four weeks, or once every five weeks.

[0038] In certain embodiments, the subject has a detectable baseline serum level of anti-ganglioside IgM antibodies.

[0039] In certain embodiments, the subject has been previously treated with IVIg. In certain embodiments, the subject has been previously stabilized with IVIg. In certain embodiments, the subject is dependent on IVIg.

[0040] In certain embodiments, the subject is not receiving concomitant IVIg. In certain embodiments, the subject does not require IVIg retreatment after administration of a C2 inhibitor. In certain embodiments, administration of the C2 inhibitor extends the time to IVIg retreatment.

[0041] In certain embodiments, the subject shows an increase in the modified Medical Research Council (mMRC) score after administration of the C2 inhibitor as compared to the subject's baseline mMRC score. In certain embodiments, the mMRC score is the mMRC-10 total score or the mMRC-14 total score.

[0042] In certain embodiments, the subject shows an improvement in grip strength after administration of the C2 inhibitor as compared to the subject's baseline grip strength.

[0043] In certain embodiments, the subject shows an increase in the MMN Rasch Construct Total Disability Scale (MMN-RODS™) score after administration of the C2 inhibitor as compared to the subject's baseline MMN-RODS™ score.

[0044] In certain embodiments, the C2 inhibitor is an antibody that specifically binds to C2.

[0045] In certain embodiments, the antibody comprises a variable heavy chain (VH) comprising the CDRH1, CDRH2, and CDRH3 amino acid sequences of the VH amino acid sequence set forth in SEQ ID NO: 7, or a variant thereof comprising 1 to 5 amino acid changes in any one of the CDRH1, CDRH2, or CDRH3 amino acid sequences; and / or a variable light chain (VL) comprising the CDRL1, CDRL2, and CDRL3 amino acid sequences of the VL amino acid sequence set forth in SEQ ID NO: 8, or a variant thereof comprising 1 to 5 amino acid changes in any one of the CDRL1, CDRL2, or CDRL3 amino acid sequences.

[0046] In certain embodiments, (a) the VH comprises the CDRH1, CDRH2, and CDRH3 amino acid sequences of SEQ ID NO: 1 or a variant thereof comprising 1 to 5 amino acid changes, SEQ ID NO: 2 or a variant thereof comprising 1 to 5 amino acid changes, and SEQ ID NO: 3 or a variant thereof comprising 1 to 5 amino acid changes, respectively; and / or (b) the VL comprises the CDRL1, CDRL2, and CDRL3 amino acid sequences of SEQ ID NO: 4 or a variant thereof comprising 1 to 5 amino acid changes, SEQ ID NO: 5 or a variant thereof comprising 1 to 5 amino acid changes, and SEQ ID NO: 6 or a variant thereof comprising 1 to 5 amino acid changes, respectively.

[0047] In certain embodiments, the antibody comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences set forth in SEQ ID NOs: 1, 2, 3, 4, 5, and 6, respectively.

[0048] In certain embodiments, the antibody comprises a VH comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, or 99% identical to the amino acid sequence set forth in SEQ ID NO: 7; and / or a VL comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, or 99% identical to the amino acid sequence set forth in SEQ ID NO: 8.

[0049] In certain embodiments, the antibody comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 7 and a VL comprising the amino acid sequence set forth in SEQ ID NO: 8. In certain embodiments, the amino acid sequence of the VH consists of the amino acid sequence set forth in SEQ ID NO: 7, and the amino acid sequence of the VL consists of the amino acid sequence set forth in SEQ ID NO: 8.

[0050] In certain embodiments, the antibody comprises a heavy chain comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, or 99% identical to the amino acid sequence set forth in SEQ ID NO: 9, and / or a light chain comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, or 99% identical to the amino acid sequence set forth in SEQ ID NO: 10.

[0051] In certain embodiments, the antibody comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 9 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 10. In certain embodiments, the amino acid sequence of the heavy chain consists of the amino acid sequence set forth in SEQ ID NO: 9, and the amino acid sequence of the light chain consists of the amino acid sequence set forth in SEQ ID NO: 10.

[0052] In one aspect, provided herein is a C2 inhibitor for use in the treatment of multifocal motor neuropathy, wherein the treatment is carried out according to the methods disclosed herein.

[0053] In one aspect, provided herein is a C2 inhibitor for use in the manufacture of a medicament for the treatment of multifocal motor neuropathy, wherein the treatment is carried out according to the methods disclosed herein.

[0054] In one aspect, provided herein is the use of a C2 inhibitor for the treatment of multifocal motor neuropathy, wherein the treatment is carried out according to the methods disclosed herein.

Mode for Carrying Out the Invention

[0055] (Detailed Description) The present disclosure is directed to methods of treating MMN with C2 inhibitors (e.g., anti-C2 antibodies). Also provided herein are specific dosing regimens for administering a C2 inhibitor that results in a rapid decrease in free C2 levels in the blood of a subject having MMN. In certain embodiments, the dosing regimen includes a loading regimen that rapidly decreases the subject's free C2 and a maintenance regimen that maintains the subject's decreased free C2 levels thereafter.

[0056] (Definitions) As used herein, the terms “antibody” and “antibodies” include full-length antibodies, antigen-binding fragments of full-length antibodies, and molecules comprising antibody CDRs, VH regions, and / or VL regions. Examples of antibodies include, but are not limited to, monoclonal antibodies, recombinantly produced antibodies, monospecific antibodies, multispecific antibodies (including bispecific antibodies), human antibodies, humanized antibodies, chimeric antibodies, immunoglobulins, synthetic antibodies, tetrameric antibodies comprising two heavy chain molecules and two light chain molecules, antibody light chain monomers, antibody heavy chain monomers, antibody light chain dimers, antibody heavy chain dimers, antibody light chain-heavy chain pairs, intrabodies, heteroconjugate antibodies, antibody-drug conjugates, single domain antibodies, monovalent antibodies, single chain antibodies or single chain Fv (scFv), camelized antibodies, affibodies, Fab fragments, F(ab')2 fragments, disulfide-linked Fv (sdFv), anti-idiotype (anti-Id) antibodies (including, e.g., anti-anti-Id antibodies), and antigen-binding fragments of any of the foregoing. In certain embodiments, the antibodies described herein refer to a polyclonal antibody population. Antibodies can be of any type of immunoglobulin molecule (e.g., IgG, IgE, IgM, IgD, IgA, or IgY), any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, or IgA2), or any subclass (e.g., IgG2a or IgG2b). In certain embodiments, the antibodies described herein are IgG antibodies, or a class (e.g., human IgG1 or IgG4) or subclass thereof. In certain embodiments, the antibody is a humanized monoclonal antibody. In certain embodiments, the antibody is a human monoclonal antibody.

[0057] As used herein, the term "CDR" or "complementary determining region" means the discontinuous antigen-combining sites found within the variable regions of heavy and light chain polypeptides. These particular regions are described, for example, by Kabat et al., J. Biol. Chem. 252, 6609-6616 (1977) and Kabat et al., Sequences of Proteins of Immunological Interest. (1991), all of which are hereby incorporated by reference in their entirety, by Chothia et al., J. Mol. Biol. 196:901-917 (1987), and by MacCallum et al., J. Mol. Biol. 262:732-745 (1996), where this definition includes the overlap or subsets of amino acid residues when compared to each other (see Table 1 below). In certain embodiments, the term "CDR" is the CDR as defined by MacCallum et al., J. Mol. Biol. 262:732-745 (1996) and by Martin A in Antibody Engineering, edited by Kontermann and Dubel, Chapter 31, pp. 422-439, Springer-Verlag, Berlin (2001), "Protein Sequence and Structure Analysis of Antibody Variable Domains". In certain embodiments, the term "CDR" is the CDR as defined by Kabat et al., J. Biol. Chem. 252, 6609-6616 (1977) and Kabat et al., Sequences of Proteins of Immunological Interest. (1991). In certain embodiments, the heavy chain CDRs and light chain CDRs of an antibody are defined using various conventions. In certain embodiments, the heavy chain CDRs and / or light chain CDRs are defined by performing a structural analysis of the antibody and identifying the residues in the variable region that are predicted to contact the epitope region of the target molecule (e.g., human C2).CDRH1, CDRH2, and CDRH3 represent the heavy chain CDRs, and CDRL1, CDRL2, and CDRL3 represent the light chain CDRs. Table 1: CDR Definitions [Table 1]

[0058] As used herein, the terms "variable region" and "variable domain" are used interchangeably and are common in the art. The variable region is typically the part of the antibody that has a highly variable sequence between antibodies and is used for the binding and specificity of a particular antibody to its specific antigen, usually part of the light or heavy chain, typically referring to approximately 110 - 120 amino acids or 110 - 125 amino acids at the amino terminus in the mature heavy chain and approximately 90 - 115 amino acids in the mature light chain. The variability of the sequence is concentrated in regions called complementarity determining regions (CDRs), while the more highly conserved regions in the variable region are called framework regions (FRs). Without wishing to be bound by any particular mechanism or theory, the CDRs of the light and heavy chains are thought to be mainly involved in the interaction and specificity of the antibody with the antigen. In certain embodiments, the variable region is a human variable region. In certain embodiments, the variable region includes rodent or mouse CDRs and human framework regions (FRs). In certain embodiments, the variable region is a primate (e.g., non-human primate) variable region. In certain embodiments, the variable region includes rodent or mouse CDRs and primate (e.g., non-human primate) framework regions (FRs).

[0059] As used herein, the terms "VH" and "VL" refer to the heavy chain variable region and the light chain variable region of an antibody, respectively, as described in Kabat et al. (1991), Sequences of Proteins of Immunological Interest (NIH Publication No. 91 - 3242, Bethesda), which is hereby incorporated by reference in its entirety.

[0060] As used herein, the term "constant region" is common in the art. The constant region is an antibody portion, such as the carboxyl-terminal portion of a light chain and / or heavy chain, that does not directly participate in the binding of an antibody to an antigen but can exhibit various effector functions, such as interaction with an Fc receptor (e.g., Fc gamma receptor).

[0061] As used herein, the term "heavy chain" when used in reference to an antibody can refer to any different type, such as alpha (α), delta (δ), epsilon (ε), gamma (γ), and mu (μ), based on the amino acid sequence of the constant region that gives rise to antibodies of the IgA, IgD, IgE, IgG, and IgM classes, including subclasses of IgG, such as IgG1, IgG2, IgG3, and IgG4.

[0062] As used herein, the term "light chain" when used in reference to an antibody can refer to any different type, such as kappa (κ) or lambda (λ), based on the amino acid sequence of the constant region. Light chain amino acid sequences are well known in the art. In certain embodiments, the light chain is a human light chain.

[0063] As used herein, the terms "specifically binds", "specifically recognizes", "immunologically specifically binds", and "immunologically specifically recognizes" are similar terms in the context of antibodies and refer to a molecule that binds to an antigen (e.g., an epitope or an immune complex) such that such binding is understood by one of ordinary skill in the art. For example, a molecule that specifically binds to an antigen will typically bind to other peptides or polypeptides with a lower affinity, as determined by, for example, an immunoassay, BIAcore®, KinExA 3000 instrument (Sapidyne Instruments, Boise, ID), or other assays known in the art. In certain embodiments, a molecule that specifically binds to an antigen binds to the antigen with a KA that is at least 2 log (e.g., a multiple of 10), 2.5 log, 3 log, 4 log greater than, or greater than, the KA when the molecule binds non-specifically to another antigen.

[0064] As used herein, the term "EU numbering system" refers to the EU numbering convention for the constant regions of antibodies, as described in Edelman G.M. et al., Proc. Natl. Acad. USA, 63, 78-85 (1969) and Kabat et al., Sequences of Proteins of Immunological Interest, U.S. Dept. Health and Human Services, 5th ed., 1991, each of which is incorporated herein by reference in its entirety.

[0065] As used herein, the term "subject" includes any human or non-human animal. In certain embodiments, the subject is human.

[0066] As used herein, the term "baseline" refers to a measurement (e.g., free C2 level) in a subject's blood, for example, prior to the first administration (e.g., intravenous or subcutaneous administration) of a treatment (e.g., a C2 inhibitor).

[0067] As used herein, the term "effective amount" in the context of administering a therapy to a subject refers to the amount of the therapy that achieves the desired prophylactic or therapeutic effect.

[0068] As used herein, the term "IVIg retreatment" refers to administering IVIg therapy to a subject who has previously been treated with IVIg. In certain embodiments, the subject is given an IVIg retreatment based on clinical deterioration. In certain embodiments, clinical deterioration is defined as a >30% decrease in grip strength of either hand (based on a 3-day average calculation) and / or at least a 2-point decrease in the mMRC-10 total score compared to the randomized day, observed continuously for at least 2 days.

[0069] As used herein, the term "IVIg-dependent" or "dependent on IVIg" refers to a subject who exhibits clinical deterioration when IVIg therapy is discontinued or who exhibits clinical improvement when IVIg therapy is initiated. In certain embodiments, a subject is considered IVIg-dependent if the subject has been stabilized on IVIg for longer than 3 months and a clinically significant deterioration has been established. In certain embodiments, a subject is considered IVIg-dependent if the subject has been stabilized on IVIg for less than 3 months and exhibits clinical improvement after initiation of IVIg therapy.

[0070] As used herein, the term "about" when referring to a measurable value, e.g., a dosage, encompasses variations of ±20%, ±15%, ±10%, ±5%, ±1%, or ±0.1% of a given value or range as is appropriate for carrying out the methods disclosed herein.

[0071] (Multifocal motor neuropathy (MMN)) (Diagnosis of MMN) The diagnosis of MMN depends on showing that the patient has a purely motor disorder affecting individual nerves, no upper motor neuron (UMN) signs, only very mild or no sensory deficits, and evidence of conduction block. These criteria are designed to distinguish this disorder from ALS (purely motor but with UMN signs), the Lewis - Sumner syndrome variant of chronic inflammatory demyelinating polyneuropathy (CIDP, similar to MMN but usually with prominent sensory loss), and "vasculitis" (a type of mononeuropathy multiplex syndrome caused by inflammatory damage to the blood vessels within the nerves that also causes sensory and motor symptoms).

[0072] To determine the diagnosis, a neurologist is usually required, and the diagnosis is based on the medical history and physical examination in addition to electrodiagnostic studies including nerve conduction studies (NCS) and needle electromyography (EMG). NCS usually shows conduction block. This can be done by showing that nerve signals cannot conduct beyond a "lesion" at some point along the nerve. For example, if a nerve is blocked in the forearm, when a stimulus is placed at the wrist, the electrical impulse can easily reach from the wrist to the hand. However, if the stimulus is applied at the elbow, the signal will not reach the hand. In MMN, sensory conduction along the same pathway should be normal. The EMG part of the examination looks for signals from the way the muscles contract. In MMN, there is a high likelihood of finding abnormalities suggesting that some proportion of the motor axons are damaged. Clinical testing for GM1 antibodies is frequently done and can be very helpful if abnormal. However, since only one - third of MMN patients have these antibodies, a negative test does not rule out the disorder. A cerebrospinal fluid examination is usually not helpful.

[0073] (Standard treatment) In 2012, the U.S. Food and Drug Administration (FDA) approved Gammagard Liquid 10% for the treatment of MMN. This agent is an intravenous immunoglobulin (IVIg), and most affected patients respond to treatment with IVIg. When treatment is initiated, rapid improvement in muscle weakness is usually seen. The effects of IVIg treatment ultimately wear off, and affected patients need to take the agent again every 2 - 6 weeks (maintenance therapy). Affected patients may become less responsive to the agent and require higher doses or more frequent maintenance therapy. If an affected patient does not respond to or becomes unresponsive to treatment with IVIg, other agents can be tried. A variety of other agents, including cyclophosphamide, rituximab, beta-interferon, mycophenolate mofetil, cyclosporine, azathioprine, and infliximab, are being tested for the treatment of MMN.

[0074] (C2 inhibitor) C2 inhibitors useful in the methods and uses provided herein include, but are not limited to, any anti-C2 antibody.

[0075] In certain embodiments, the C2 inhibitor is an antibody that specifically binds to the C2b portion of C2 in a pH- and Ca2+-dependent manner. In certain embodiments, the C2 inhibitor is an anti-C2b antibody. As used herein, C2b refers to the smaller 30 kDa fragment of the complement protein C2. In certain embodiments, the antibody inhibits the function of C2 and blocks downstream complement activation.

[0076] In certain embodiments, the antibody comprises a heavy chain variable region (VH) comprising the CDRH1, CDRH2, and CDRH3 amino acid sequences of the VH amino acid sequence shown in SEQ ID NO: 7, or a variant thereof comprising 1 to 5 amino acid changes in any one of the CDRH1, CDRH2, or CDRH3 amino acid sequences; and / or a light chain variable region (VL) comprising the CDRL1, CDRL2, and CDRL3 amino acid sequences of the VL amino acid sequence shown in SEQ ID NO: 8, or a variant thereof comprising 1 to 5 amino acid changes in any one of the CDRL1, CDRL2, or CDRL3 amino acid sequences.

[0077] In certain embodiments, (a) the VH comprises the CDRH1, CDRH2, and CDRH3 amino acid sequences of SEQ ID NO: 1 or a variant thereof comprising 1 to 5 amino acid changes, SEQ ID NO: 2 or a variant thereof comprising 1 to 5 amino acid changes, and SEQ ID NO: 3 or a variant thereof comprising 1 to 5 amino acid changes, respectively; and / or (b) the VL comprises the CDRL1, CDRL2, and CDRL3 amino acid sequences of SEQ ID NO: 4 or a variant thereof comprising 1 to 5 amino acid changes, SEQ ID NO: 5 or a variant thereof comprising 1 to 5 amino acid changes, and SEQ ID NO: 6 or a variant thereof comprising 1 to 5 amino acid changes, respectively.

[0078] In certain embodiments, the antibody comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, and 6, respectively.

[0079] In certain embodiments, the antibody comprises a VH comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence shown in SEQ ID NO: 7; and / or a VL comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence shown in SEQ ID NO: 8.

[0080] In certain embodiments, the antibody comprises a VH comprising the amino acid sequence shown in SEQ ID NO: 7 and a VL comprising the amino acid sequence shown in SEQ ID NO: 8. In certain embodiments, the amino acid sequence of VH consists of the amino acid sequence shown in SEQ ID NO: 7, and the amino acid sequence of VL consists of the amino acid sequence shown in SEQ ID NO: 8.

[0081] In certain embodiments, the antibody comprises a heavy chain comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence shown in SEQ ID NO: 9 and / or a light chain comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence shown in SEQ ID NO: 10.

[0082] In certain embodiments, the antibody comprises a heavy chain comprising the amino acid sequence shown in SEQ ID NO: 9 and a light chain comprising the amino acid sequence shown in SEQ ID NO: 10. In certain embodiments, the amino acid sequence of the heavy chain consists of the amino acid sequence shown in SEQ ID NO: 9, and the amino acid sequence of the light chain consists of the amino acid sequence shown in SEQ ID NO: 10.

[0083] In certain embodiments, the antibody is ARGX-117, the sequence of which is provided in Table 2 below. Table 2: Amino Acid Sequence of ARGX-117

Table 2

[0084] ARGX-117 binds to human and cynomolgus C2 with an affinity for human C2 in the range of 0.109 nM to 2.02 nM and an affinity for cynomolgus C2 in the range of 0.056 nM to 0.13 nM, respectively, in a pH- and Ca2 + -dependent manner. In any one embodiment of the methods disclosed herein, the C2 inhibitor is pH- and Ca2 +In a dependent manner, it binds to human and cynomolgus C2 with an affinity for human C2 in the range of 0.109 nM to 2.02 nM and an affinity for cynomolgus C2 in the range of 0.056 nM to 0.13 nM, respectively. ARGX-117 does not cross-react with C2 derived from rat, rabbit, hamster, mouse, and guinea pig. Epitope mapping revealed that ARGX-117 binds mainly to the sushi 2 domain of C2. In any one embodiment of the methods disclosed herein, the C2 inhibitor binds to the sushi 2 domain of C2.

[0085] ARGX-117 inhibits the classical and lectin pathways of the complement system but has no effect on the alternative pathway. In any one embodiment of the methods disclosed herein, the C2 inhibitor inhibits the classical and lectin pathways of the complement system. In any one embodiment of the methods disclosed herein, the C2 inhibitor does not inhibit the alternative pathway.

[0086] (Methods and dosing regimens) The present disclosure shows that C2 inhibitors are highly effective in treating multifocal motor neuropathy (MMN). Accordingly, the present disclosure broadly targets methods of treating MMN with C2 inhibitors. Also provided herein is a specific dosing regimen for administering a C2 inhibitor that results in a rapid decrease in free C2 levels in the blood of a subject having MMN.

[0087] In one aspect, provided herein is a method of treating multifocal motor neuropathy (MMN) in a subject in need thereof, the method comprising administering to the subject an effective amount of a C2 inhibitor.

[0088] In certain embodiments, the C2 inhibitor is administered at a dose of about 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of about 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of about 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of about 5 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of about 10 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of about 15 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of about 30 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dose of about 60 mg / kg.

[0089] In certain embodiments, the C2 inhibitor is administered at a dosage of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dosage of 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered at a dosage of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0090] In certain embodiments, the C2 inhibitor is administered at a fixed dosage of about 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered at a fixed dosage of about 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0091] In certain embodiments, the C2 inhibitor is administered at a fixed dosage of 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered at a fixed dosage of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0092] In certain embodiments, the C2 inhibitor is administered intravenously or subcutaneously. In certain embodiments, the C2 inhibitor is administered intravenously. In certain embodiments, the C2 inhibitor is administered subcutaneously.

[0093] In certain embodiments, the C2 inhibitor is administered once a week. In certain embodiments, the C2 inhibitor is administered once every two weeks. In certain embodiments, the C2 inhibitor is administered once every four weeks. In certain embodiments, the C2 inhibitor is administered once every five weeks. In certain embodiments, the C2 inhibitor is administered once every six weeks. In certain embodiments, the C2 inhibitor is administered once every seven weeks. In certain embodiments, the C2 inhibitor is administered once every eight weeks.

[0094] In certain embodiments, the C2 inhibitor is administered once a week at a dose of about 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once a week at a dose of about 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once a week at a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once a week at a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once a week at a dose of about 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once a week at a dose of about 5 mg / kg. In certain embodiments, the C2 inhibitor is administered once a week at a dose of about 10 mg / kg. In certain embodiments, the C2 inhibitor is administered once a week at a dose of about 15 mg / kg. In certain embodiments, the C2 inhibitor is administered once a week at a dose of about 30 mg / kg. In certain embodiments, the C2 inhibitor is administered once a week at a dose of about 60 mg / kg.

[0095] In certain embodiments, the C2 inhibitor is administered once a week at a dose of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once a week at a dose of 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once a week at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once a week at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once a week at a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0096] In certain embodiments, the C2 inhibitor is administered once a week at a fixed dose of about 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once a week at a fixed dose of about 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0097] In certain embodiments, the C2 inhibitor is administered once a week at a fixed dose of 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once a week at a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0098] In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of about 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of about 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of about 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of about 5 mg / kg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of about 10 mg / kg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of about 15 mg / kg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of about 30 mg / kg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of about 60 mg / kg.

[0099] In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0100] In certain embodiments, the C2 inhibitor is administered once every two weeks at a fixed dose of about 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a fixed dose of about 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0101] In certain embodiments, the C2 inhibitor is administered once every two weeks at a fixed dose of 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once every two weeks at a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0102] In certain embodiments, the C2 inhibitor is administered once every three weeks at a dosage of about 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a dosage of about 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a dosage of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a dosage of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a dosage of about 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a dosage of about 5 mg / kg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a dosage of about 10 mg / kg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a dosage of about 15 mg / kg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a dosage of about 30 mg / kg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a dosage of about 60 mg / kg.

[0103] In certain embodiments, the C2 inhibitor is administered once every three weeks at a dose of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a dose of 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0104] In certain embodiments, the C2 inhibitor is administered once every three weeks at a fixed dose of about 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a fixed dose of about 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0105] In certain embodiments, the C2 inhibitor is administered once every three weeks at a fixed dose of 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once every three weeks at a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0106] In certain embodiments, the C2 inhibitor is administered once every four weeks at a dose of about 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a dose of about 4 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a dose of about 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a dose of about 5 mg / kg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a dose of about 10 mg / kg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a dose of about 15 mg / kg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a dose of about 30 mg / kg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a dose of about 60 mg / kg.

[0107] In certain embodiments, the C2 inhibitor is administered once every four weeks at a dosage of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a dosage of 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a dosage of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0108] In certain embodiments, the C2 inhibitor is administered once every four weeks at a fixed dosage of about 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a fixed dosage of about 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0109] In certain embodiments, the C2 inhibitor is administered once every four weeks at a fixed dosage of 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once every four weeks at a fixed dosage of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0110] In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a dose of about 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a dose of about 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a dose of about 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a dose of about 5 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 10 weeks at a dose of about 5 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 15 weeks at a dose of about 5 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 30 weeks at a dose of about 5 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 60 weeks at a dose of about 5 mg / kg.

[0111] In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a dose of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a dose of 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0112] In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a fixed dose of about 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a fixed dose of about 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0113] In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a fixed dose of 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once every 5 weeks at a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0114] In certain embodiments, the C2 inhibitor is administered once every six weeks at a dosage of about 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every six weeks at a dosage of about 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every six weeks at a dosage of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every six weeks at a dosage of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once every six weeks at a dosage of about 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every six weeks at a dosage of about 5 mg / kg. In certain embodiments, the C2 inhibitor is administered once every six weeks at a dosage of about 10 mg / kg. In certain embodiments, the C2 inhibitor is administered once every six weeks at a dosage of about 15 mg / kg. In certain embodiments, the C2 inhibitor is administered once every six weeks at a dosage of about 30 mg / kg. In certain embodiments, the C2 inhibitor is administered once every six weeks at a dosage of about 60 mg / kg.

[0115] In certain embodiments, the C2 inhibitor is administered once every 6 weeks at a dose of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 6 weeks at a dose of 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 6 weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 6 weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 6 weeks at a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0116] In certain embodiments, the C2 inhibitor is administered once every 6 weeks at a fixed dose of about 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once every 6 weeks at a fixed dose of about 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0117] In certain embodiments, the C2 inhibitor is administered once every 6 weeks at a fixed dose of 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once every 6 weeks at a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0118] In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of about 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of about 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of about 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of about 5 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of about 10 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of about 15 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of about 30 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of about 60 mg / kg.

[0119] In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0120] In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a fixed dose of about 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a fixed dose of about 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0121] In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a fixed dose of 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once every 7 weeks at a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0122] In certain embodiments, the C2 inhibitor is administered once every 8 weeks at a dose of about 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 8 weeks at a dose of about 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 8 weeks at a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 8 weeks at a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 8 weeks at a dose of about 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 8 weeks at a dose of about 5 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 8 weeks at a dose of about 10 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 8 weeks at a dose of about 15 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 8 weeks at a dose of about 30 mg / kg. In certain embodiments, the C2 inhibitor is administered once every 8 weeks at a dose of about 60 mg / kg.

[0123] In certain embodiments, the C2 inhibitor is administered once every eight weeks at a dose of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every eight weeks at a dose of 5 mg / kg to 60 mg / kg. In certain embodiments, the C2 inhibitor is administered once every eight weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the C2 inhibitor is administered once every eight weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the C2 inhibitor is administered once every eight weeks at a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0124] In certain embodiments, the C2 inhibitor is administered once every eight weeks at a fixed dose of about 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once every eight weeks at a fixed dose of about 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0125] In certain embodiments, the C2 inhibitor is administered once every eight weeks at a fixed dose of 500 mg to 1500 mg. In certain embodiments, the C2 inhibitor is administered once every eight weeks at a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0126] In certain embodiments, the C2 inhibitor is administered intravenously at a dose of 10 mg / kg once a week or once every two weeks. In certain embodiments, the C2 inhibitor is administered intravenously at a dose of 30 mg / kg once a week or once every two weeks. In certain embodiments, the C2 inhibitor is administered intravenously at a dose of 60 mg / kg once a week or once every two weeks. In certain embodiments, the C2 inhibitor is administered intravenously at a dose of 15 mg / kg once a week or once every two weeks. In certain embodiments, the C2 inhibitor is administered intravenously at a dose of 5 mg / kg once a week, once every two weeks, or once every four weeks.

[0127] In certain embodiments, the C2 inhibitor is administered according to a loading regimen that reduces the level of free C2 in the subject's blood to or below a threshold level.

[0128] In certain embodiments, the method further comprises a maintenance regimen after the loading regimen, wherein the maintenance regimen comprises administration of the C2 inhibitor by a regimen that maintains the level of free C2 in the subject's blood at or below the threshold level.

[0129] In certain embodiments, the threshold level is about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, or 0.8 μg / mL. In certain embodiments, the threshold level is about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20% of the baseline level of free C2 of the subject. In certain embodiments, the threshold level is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, or 0.8 μg / mL. In certain embodiments, the threshold level is 0.1, 0.2, 0.3, 0.4 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20% of the baseline level of free C2 of the subject. As used herein, "baseline level of free C2" refers to the level or concentration of circulating (serum or plasma) C2 in the subject prior to the first administration of a C2 inhibitor (e.g., ARGX-117). C2 levels can be measured using any suitable technique. See, for example, Tange CE et al., Clin Chem Lab Med 2018; 56(9): 1498-1506.

[0130] In certain embodiments, the dosing regimen is a single initial dose and one or more subsequent doses. In certain embodiments, each of the one or more subsequent doses is an amount less than the single initial dose. In certain embodiments, each of the one or more subsequent doses is an amount greater than the single initial dose. In certain embodiments, each of the one or more subsequent doses is an amount equal to the amount of the single initial dose.

[0131] In certain embodiments, a single initial dose is followed by 1, 2, 3, 4, 5, or 6 subsequent doses. In certain embodiments, the subsequent doses are administered once a week or once every two weeks. In certain embodiments, a single initial dose is followed by 1, 2, 3, 4, 5, or 6 subsequent doses that are administered once a week. In certain embodiments, a single initial dose is followed by 1, 2, 3, 4, 5, or 6 subsequent doses that are administered once every two weeks. In certain embodiments, a single initial dose is followed by 4 subsequent doses that are administered once a week.

[0132] In certain embodiments, the first subsequent dose is administered one week after the single initial dose. In certain embodiments, the first subsequent dose is administered ten days after the single initial dose. In certain embodiments, the first subsequent dose is administered two weeks after the single initial dose.

[0133] In certain embodiments, the single initial dose is a dose of about 0.1 mg / kg to 100 mg / kg. In certain embodiments, the single initial dose is a dose of about 10 mg / kg to 60 mg / kg. In certain embodiments, the single initial dose is a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the single initial dose is a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the single initial dose is a dose of about 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, the single initial dose is a dose of about 15 mg / kg. In certain embodiments, the single initial dose is a dose of about 30 mg / kg. In certain embodiments, the single initial dose is a dose of about 60 mg / kg.

[0134] In certain embodiments, a single initial dose is a dose of from 0.1 mg / kg to 100 mg / kg. In certain embodiments, a single initial dose is a dose of from 10 mg / kg to 60 mg / kg. In certain embodiments, a single initial dose is a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, a single initial dose is a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, a single initial dose is a dose of 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0135] In certain embodiments, a single initial dose is a fixed dose of from about 500 mg to 1500 mg. In certain embodiments, a single initial dose is a fixed dose of about 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0136] In certain embodiments, a single initial dose is a fixed dose of from 500 mg to 1500 mg. In certain embodiments, a single initial dose is a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0137] In certain embodiments, the subsequent doses are each a dose of from about 0.1 mg / kg to 100 mg / kg. In certain embodiments, the subsequent doses are each a dose of from about 5 mg / kg to 60 mg / kg. In certain embodiments, the subsequent doses are each a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the subsequent doses are each a dose of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the subsequent doses are each a dose of about 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, the subsequent doses are each a dose of about 5 mg / kg. In certain embodiments, the subsequent doses are each a dose of about 10 mg / kg. In certain embodiments, the subsequent doses are each a dose of about 30 mg / kg.

[0138] In certain embodiments, the subsequent doses are each in a dose range of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the subsequent doses are each in a dose range of 5 mg / kg to 60 mg / kg. In certain embodiments, the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the subsequent doses are each a dose of 5 mg / kg, 10 mg / kg, 30 mg / kg, or 60 mg / kg.

[0139] In certain embodiments, the subsequent doses are each a fixed dose of about 500 mg to 1500 mg. In certain embodiments, the subsequent doses are each a fixed dose of about 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0140] In certain embodiments, the subsequent doses are each a fixed dose of 500 mg to 1500 mg. In certain embodiments, the subsequent doses are each a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0141] In certain embodiments, the single initial dose is a dose of 0.1 mg / kg, and the subsequent doses are each a dose in the range of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the single initial dose is a dose of 0.1 mg / kg, and the subsequent doses are each a dose in the range of 5 mg / kg to 60 mg / kg. In certain embodiments, the single initial dose is a dose of 0.1 mg / kg, and the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the single initial dose is a dose of 0.1 mg / kg, and the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the single initial dose is a dose of 0.1 mg / kg, and the subsequent doses are each a dose of 5 mg / kg, 15 mg / kg, 10 mg / kg, 30 mg / kg, or 60 mg / kg.

[0142] In certain embodiments, the single initial dose is a dose of 0.1 mg / kg, and the subsequent doses are each a fixed dose of 500 mg to 1500 mg. In certain embodiments, the single initial dose is a dose of 0.1 mg / kg, and the subsequent doses are each a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0143] In certain embodiments, the single initial dose is a dose of 0.5 mg / kg and the subsequent doses are each a dose of from 0.1 mg / kg to 100 mg / kg. In certain embodiments, the single initial dose is a dose of 0.5 mg / kg and the subsequent doses are each a dose of from 5 mg / kg to 60 mg / kg. In certain embodiments, the single initial dose is a dose of 0.5 mg / kg and the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the single initial dose is a dose of 0.5 mg / kg and the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the single initial dose is a dose of 0.5 mg / kg and the subsequent doses are each a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0144] In certain embodiments, the single initial dose is a dose of 0.5 mg / kg and the subsequent doses are each a fixed dose of from 500 mg to 1500 mg. In certain embodiments, the single initial dose is a dose of 0.5 mg / kg and the subsequent doses are each a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0145] In certain embodiments, the single initial dose is a dose of 2.5 mg / kg, and the subsequent doses are each a dose of from 0.1 mg / kg to 100 mg / kg. In certain embodiments, the single initial dose is a dose of 2.5 mg / kg, and the subsequent doses are each a dose of from 5 mg / kg to 60 mg / kg. In certain embodiments, the single initial dose is a dose of 2.5 mg / kg, and the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the single initial dose is a dose of 2.5 mg / kg, and the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the single initial dose is a dose of 2.5 mg / kg, and the subsequent doses are each a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0146] In certain embodiments, the single initial dose is a dose of 2.5 mg / kg, and the subsequent doses are each a fixed dose of from 500 mg to 1500 mg. In certain embodiments, the single initial dose is a dose of 2.5 mg / kg, and the subsequent doses are each a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0147] In certain embodiments, the single initial dose is a dose of 10 mg / kg and the subsequent doses are each a dose in the range of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the single initial dose is a dose of 10 mg / kg and the subsequent doses are each a dose in the range of 5 mg / kg to 60 mg / kg. In certain embodiments, the single initial dose is a dose of 10 mg / kg and the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the single initial dose is a dose of 10 mg / kg and the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the single initial dose is a dose of 10 mg / kg and the subsequent doses are each a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0148] In certain embodiments, the single initial dose is a dose of 10 mg / kg and the subsequent doses are each a fixed dose in the range of 500 mg to 1500 mg. In certain embodiments, the single initial dose is a dose of 10 mg / kg and the subsequent doses are each a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0149] In certain embodiments, the single initial dose is a dose of 15 mg / kg, and the subsequent doses are each a dose of from 0.1 mg / kg to 100 mg / kg. In certain embodiments, the single initial dose is a dose of 15 mg / kg, and the subsequent doses are each a dose of from 5 mg / kg to 60 mg / kg. In certain embodiments, the single initial dose is a dose of 15 mg / kg, and the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the single initial dose is a dose of 15 mg / kg, and the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the single initial dose is a dose of 15 mg / kg, and the subsequent doses are each a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, the single initial dose is a dose of 15 mg / kg, and the subsequent doses are each a dose of 5 mg / kg.

[0150] In certain embodiments, the single initial dose is a dose of 15 mg / kg, and the subsequent doses are each a fixed dose of from 500 mg to 1500 mg. In certain embodiments, the single initial dose is a dose of 15 mg / kg, and the subsequent doses are each a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0151] In certain embodiments, the single initial dose is a dose of 30 mg / kg, and the subsequent doses are each a dose in the range of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the single initial dose is a dose of 30 mg / kg, and the subsequent doses are each a dose in the range of 5 mg / kg to 60 mg / kg. In certain embodiments, the single initial dose is a dose of 30 mg / kg, and the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the single initial dose is a dose of 30 mg / kg, and the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the single initial dose is a dose of 30 mg / kg, and the subsequent doses are each a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, the single initial dose is a dose of 30 mg / kg, and the subsequent doses are each a dose of 10 mg / kg.

[0152] In certain embodiments, the single initial dose is a dose of 30 mg / kg, and the subsequent doses are each a fixed dose in the range of 500 mg to 1500 mg. In certain embodiments, the single initial dose is a dose of 30 mg / kg, and the subsequent doses are each a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0153] In certain embodiments, a single initial dose is a dose of 60 mg / kg and subsequent doses are each a dose of from 0.1 mg / kg to 100 mg / kg. In certain embodiments, a single initial dose is a dose of 60 mg / kg and subsequent doses are each a dose of from 5 mg / kg to 60 mg / kg. In certain embodiments, a single initial dose is a dose of 60 mg / kg and subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, a single initial dose is a dose of 60 mg / kg and subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, a single initial dose is a dose of 60 mg / kg and subsequent doses are each a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. In certain embodiments, a single initial dose is a dose of 60 mg / kg and subsequent doses are each a dose of 30 mg / kg.

[0154] In certain embodiments, a single initial dose is a dose of 60 mg / kg and subsequent doses are each a fixed dose of from 500 mg to 1500 mg. In certain embodiments, a single initial dose is a dose of 60 mg / kg and subsequent doses are each a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0155] In certain embodiments, the single initial dose is a dose of 80 mg / kg and the subsequent doses are each a dose of from 0.1 mg / kg to 100 mg / kg. In certain embodiments, the single initial dose is a dose of 80 mg / kg and the subsequent doses are each a dose of from 5 mg / kg to 60 mg / kg. In certain embodiments, the single initial dose is a dose of 80 mg / kg and the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the single initial dose is a dose of 80 mg / kg and the subsequent doses are each a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the single initial dose is a dose of 80 mg / kg and the subsequent doses are each a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0156] In certain embodiments, the single initial dose is a dose of 80 mg / kg and the subsequent doses are each a fixed dose of from 500 mg to 1500 mg. In certain embodiments, the single initial dose is a dose of 80 mg / kg and the subsequent doses are each a fixed dose of 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0157] In certain embodiments, the single initial dose is a fixed dose of 1200 mg, and the subsequent doses are each in the range of 0.1 mg / kg to 100 mg / kg. In certain embodiments, the single initial dose is a fixed dose of 1200 mg, and the subsequent doses are each in the range of 5 mg / kg to 60 mg / kg. In certain embodiments, the single initial dose is a fixed dose of 1200 mg, and the subsequent doses are each 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 7.5 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or 100 mg / kg. In certain embodiments, the single initial dose is a fixed dose of 1200 mg, and the subsequent doses are each 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. In certain embodiments, the single initial dose is a fixed dose of 1200 mg, and the subsequent doses are each 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg.

[0158] In certain embodiments, the single initial dose is a fixed dose of 1200 mg, and the subsequent doses are each a fixed dose of 500 mg to 1500 mg. In certain embodiments, the single initial dose is a fixed dose of 1200 mg, and the subsequent doses are each 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg.

[0159] In certain embodiments, a single initial dose is 30 mg / kg and subsequent doses are each 10 mg / kg. In certain embodiments, a single initial dose is 60 mg / kg and subsequent doses are each 30 mg / kg. In certain embodiments, a single initial dose is 15 mg / kg and subsequent doses are each 5 mg / kg.

[0160] In certain embodiments, the loading regimen is administered intravenously or subcutaneously. In certain embodiments, the loading regimen is administered intravenously. In certain embodiments, the loading regimen is administered subcutaneously. In certain embodiments, a single initial dose is administered intravenously and subsequent doses are administered subcutaneously. In certain embodiments, a single initial dose is administered subcutaneously and subsequent doses are administered intravenously. In certain embodiments, both the single initial dose and subsequent doses are administered intravenously. In certain embodiments, both the single initial dose and subsequent doses are administered subcutaneously.

[0161] In certain embodiments, the loading regimen reduces the level of free C2 to or below the threshold level in about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days. In certain embodiments, the loading regimen reduces the level of free C2 to or below the threshold level in 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days. In certain embodiments, the loading regimen reduces the level of free C2 to or below the threshold level in about 1, 2, 3, 4, 5, 6, 7, or 8 weeks. In certain embodiments, the loading regimen reduces the level of free C2 to or below the threshold level in 1, 2, 3, 4, 5, 6, 7, or 8 weeks.

[0162] In certain embodiments, the maintenance regimen is a dose of about 0.1 - 100 mg / kg administered once every 1, 2, 3, 4, 5, 6, or 8 weeks. In certain embodiments, the maintenance regimen is a dose of 0.1 - 100 mg / kg administered once every 1, 2, 3, 4, 5, 6, or 8 weeks.

[0163] In certain embodiments, the maintenance regimen is a dose of about 0.1 to 100 mg / kg administered once a week. In certain embodiments, the maintenance regimen is a dose of about 0.1 to 100 mg / kg administered once every two weeks. In certain embodiments, the maintenance regimen is a dose of about 0.1 to 100 mg / kg administered once every three weeks. In certain embodiments, the maintenance regimen is a dose of about 0.1 to 100 mg / kg administered once every four weeks. In certain embodiments, the maintenance regimen is a dose of about 0.1 to 100 mg / kg administered once every five weeks. In certain embodiments, the maintenance regimen is a dose of about 0.1 to 100 mg / kg administered once every six weeks. In certain embodiments, the maintenance regimen is a dose of about 0.1 to 100 mg / kg administered once every seven weeks. In certain embodiments, the maintenance regimen is a dose of about 0.1 to 100 mg / kg administered once every eight weeks.

[0164] In certain embodiments, the maintenance regimen is a dose of 0.1 to 100 mg / kg administered once a week. In certain embodiments, the maintenance regimen is a dose of 0.1 to 100 mg / kg administered once every two weeks. In certain embodiments, the maintenance regimen is a dose of 0.1 to 100 mg / kg administered once every three weeks. In certain embodiments, the maintenance regimen is a dose of 0.1 to 100 mg / kg administered once every four weeks. In certain embodiments, the maintenance regimen is a dose of 0.1 to 100 mg / kg administered once every five weeks. In certain embodiments, the maintenance regimen is a dose of 0.1 to 100 mg / kg administered once every six weeks. In certain embodiments, the maintenance regimen is a dose of 0.1 to 100 mg / kg administered once every seven weeks. In certain embodiments, the maintenance regimen is a dose of 0.1 to 100 mg / kg administered once every eight weeks.

[0165] In certain embodiments, the maintenance regimen is a dosage of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once a week. In certain embodiments, the maintenance regimen is a dosage of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every two weeks. In certain embodiments, the maintenance regimen is a dosage of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every three weeks. In certain embodiments, the maintenance regimen is a dosage of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every four weeks. In certain embodiments, the maintenance regimen is a dosage of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every five weeks. In certain embodiments, the maintenance regimen is a dosage of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every six weeks. In certain embodiments, the maintenance regimen is a dosage of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every seven weeks. In certain embodiments, the maintenance regimen is a dosage of about 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every eight weeks.

[0166] In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once a week. In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every two weeks. In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every three weeks. In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every four weeks. In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every five weeks. In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every six weeks. In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every seven weeks. In certain embodiments, the maintenance regimen is a dosage of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg administered once every eight weeks.

[0167] In certain embodiments, the maintenance regimen is a dose of about 5 mg / kg administered once every four weeks. In certain embodiments, the maintenance regimen is a dose of about 10 mg / kg administered once every two weeks. In certain embodiments, the maintenance regimen is a dose of about 30 mg / kg administered once every two weeks.

[0168] In certain embodiments, the maintenance regimen is a fixed dose of about 500 mg to 1500 mg administered once every one, two, three, four, five, six, seven, or eight weeks. In certain embodiments, the maintenance regimen is a fixed dose of about 1200 mg administered once every one, two, three, four, five, six, seven, or eight weeks.

[0169] In certain embodiments, the maintenance regimen is a fixed dose of 500 mg to 1500 mg administered once every one, two, three, four, five, six, seven, or eight weeks. In certain embodiments, the maintenance regimen is a fixed dose of 1200 mg administered once every one, two, three, four, five, six, seven, or eight weeks.

[0170] In certain embodiments, the maintenance regimen is administered 1, 2, 3, 4, 5, 6, 7, or 8 weeks after the loading regimen. In certain embodiments, the maintenance regimen is administered when the level of free C2 in the subject's blood exceeds a threshold level.

[0171] In certain embodiments, the threshold level is about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1.0 μg / mL. In certain embodiments, the threshold level is about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40% of the baseline level of free C2 in the subject. In certain embodiments, the threshold level is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1.0 μg / mL. In certain embodiments, the threshold level is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40% of the baseline level of free C2 in the subject.

[0172] In certain embodiments, the maintenance regimen is administered intravenously or subcutaneously. In certain embodiments, the maintenance regimen is administered intravenously. In certain embodiments, the maintenance regimen is administered subcutaneously.

[0173] In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.1 mg / kg administered once a week. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.1 mg / kg administered once every two weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.1 mg / kg administered once every three weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.1 mg / kg administered once every four weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.1 mg / kg administered once every five weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.1 mg / kg administered once every six weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.1 mg / kg administered once every seven weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.1 mg / kg administered once every eight weeks.

[0174] In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.5 mg / kg administered once a week. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.5 mg / kg administered once every two weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.5 mg / kg administered once every three weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.5 mg / kg administered once every four weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.5 mg / kg administered once every five weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.5 mg / kg administered once every six weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.5 mg / kg administered once every seven weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 0.5 mg / kg administered once every eight weeks.

[0175] In one embodiment, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 2.5 mg / kg administered once a week. In one embodiment, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 2.5 mg / kg administered once every two weeks. In one embodiment, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 2.5 mg / kg administered once every three weeks. In one embodiment, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 2.5 mg / kg administered once every four weeks. In one embodiment, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 2.5 mg / kg administered once every five weeks. In one embodiment, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 2.5 mg / kg administered once every six weeks. In one embodiment, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 2.5 mg / kg administered once every seven weeks. In one embodiment, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 2.5 mg / kg administered once every eight weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 5 mg / kg administered once a week. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 5 mg / kg administered once every two weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 5 mg / kg administered once every three weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 5 mg / kg administered once every four weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 5 mg / kg administered once every five weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 5 mg / kg administered once every six weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 5 mg / kg administered once every seven weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 5 mg / kg administered once every eight weeks.

[0176] In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 10 mg / kg administered once a week. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 10 mg / kg administered once every two weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 10 mg / kg administered once every three weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 10 mg / kg administered once every four weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 10 mg / kg administered once every five weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 10 mg / kg administered once every six weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 10 mg / kg administered once every seven weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 10 mg / kg administered once every eight weeks.

[0177] In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 15 mg / kg administered once a week. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 15 mg / kg administered once every two weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 15 mg / kg administered once every three weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 15 mg / kg administered once every four weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 15 mg / kg administered once every five weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 15 mg / kg administered once every six weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 15 mg / kg administered once every seven weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 15 mg / kg administered once every eight weeks.

[0178] In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 30 mg / kg administered once a week. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 30 mg / kg administered once every two weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 30 mg / kg administered once every three weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 30 mg / kg administered once every four weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 30 mg / kg administered once every five weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 30 mg / kg administered once every six weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 30 mg / kg administered once every seven weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 30 mg / kg administered once every eight weeks.

[0179] In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 60 mg / kg administered once a week. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 60 mg / kg administered once every two weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 60 mg / kg administered once every three weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 60 mg / kg administered once every four weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 60 mg / kg administered once every five weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 60 mg / kg administered once every six weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 60 mg / kg administered once every seven weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 60 mg / kg administered once every eight weeks.

[0180] In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 80 mg / kg administered once a week. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 80 mg / kg administered once every two weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 80 mg / kg administered once every three weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 80 mg / kg administered once every four weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 80 mg / kg administered once every five weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 80 mg / kg administered once every six weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 80 mg / kg administered once every seven weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a dose of 80 mg / kg administered once every eight weeks.

[0181] In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a fixed dose of 1200 mg administered once a week. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a fixed dose of 1200 mg administered once every two weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a fixed dose of 1200 mg administered once every three weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a fixed dose of 1200 mg administered once every four weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a fixed dose of 1200 mg administered once every five weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a fixed dose of 1200 mg administered once every six weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a fixed dose of 1200 mg administered once every seven weeks. In certain embodiments, the loading regimen is any one of the loading regimens described herein, and the maintenance regimen is a fixed dose of 1200 mg administered once every eight weeks.

[0182] In certain embodiments, the loading regimen is a single initial dose of 0.1 mg / kg to 100 mg / kg; and four subsequent doses of 0.1 mg / kg to 100 mg / kg each, administered once a week or once every two weeks, starting one week after the single initial dose; and the maintenance regimen is a dose of 0.1 mg / kg to 100 mg / kg administered once every two weeks or once every four weeks.

[0183] In certain embodiments, the loading regimen is a single initial fixed dose of 500 mg to 1500 mg; and four subsequent doses of 500 mg to 1500 mg each, administered once a week or once every two weeks, starting one week after the single initial dose; and the maintenance regimen is a dose of 500 mg to 1500 mg, administered once every two weeks or once every four weeks.

[0184] In certain embodiments, the loading regimen is a single initial dose of 60 mg / kg; and four subsequent doses of 30 mg / kg each, administered once a week, starting one week after the single initial dose; and the maintenance regimen is a dose of 30 mg / kg, administered once every two weeks.

[0185] In certain embodiments, the loading regimen is a single initial dose of 30 mg / kg; and four subsequent doses of 10 mg / kg each, administered once a week, starting one week after the single initial dose; and the maintenance regimen is a dose of 10 mg / kg, administered once every two weeks.

[0186] In certain embodiments, the loading regimen is a single initial dose of 15 mg / kg; and four subsequent doses of 5 mg / kg each, administered once a week, starting one week after the single initial dose; and the maintenance regimen is a dose of 5 mg / kg, administered once every four weeks.

[0187] In certain embodiments, the maintenance regimen starts one week after the last subsequent dose of the loading regimen. In certain embodiments, the maintenance regimen starts 10 days after the last subsequent dose of the loading regimen. In certain embodiments, the maintenance regimen starts two weeks after the last subsequent dose of the loading regimen. In certain embodiments, the maintenance regimen starts three weeks after the last subsequent dose of the loading regimen. In certain embodiments, the maintenance regimen starts four weeks after the last subsequent dose of the loading regimen.

[0188] In certain embodiments, the loading regimen is administered intravenously and the maintenance regimen is administered subcutaneously. In certain embodiments, the loading regimen is administered subcutaneously and the maintenance regimen is administered intravenously. In certain embodiments, both the loading regimen and the maintenance regimen are administered intravenously. In certain embodiments, both the loading regimen and the maintenance regimen are administered subcutaneously.

[0189] In certain embodiments, the subject's motor strength and / or the subject's sensory symptoms are improved compared to the subject's motor strength and / or the subject's sensory symptoms achieved with standard therapy using intravenous immunoglobulin (IVIg). Sensory symptoms include paresthesia (a tingling or prickling sensation usually felt in the hands, arms, legs, or feet, but which can also occur in other parts of the body), sensory hypoesthesia (impairment or decrease in tactile sensitivity), or a combination of both.

[0190] In certain embodiments, the subject exhibits a decrease in the level of free C2 in the subject's blood following administration of a C2 inhibitor as compared to the baseline level of free C2 in the subject's blood. In certain embodiments, the level of free C2 in the subject's blood is decreased by at least about 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% as compared to the baseline level of free C2 in the subject's blood. Since the complement system is a cascade system that can be disrupted in MMN patients (imbalanced complement system or overactivation of the complement system can cause inflammation and subsequent tissue (e.g., motor nerve) damage in MMN patients), it is surprising that a decrease of at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% in the subject's free C2 level compared to the baseline level of free C2 is sufficient to effectively treat MMN patients. It was not generally known how much of a free C2 level could still be present in the subject such that the complement system could regain balance in MMN patients in response to treatment with a C2 inhibitor (e.g., ARGX-117), thereby effectively treating MMN patients.

[0191] In certain embodiments, the method further comprises administering an additional therapeutic agent to the subject. In certain embodiments, the additional therapeutic agent is IVIg. In certain embodiments, the additional therapeutic agent is rituximab, eculizumab, cyclophosphamide, or mycophenolate mofetil.

[0192] In certain embodiments, IVIg is administered to the subject once every two weeks, once every three weeks, once every four weeks, or once every five weeks.

[0193] In certain embodiments, the subject has a detectable baseline serum level of an anti-ganglioside IgM antibody. In certain embodiments, the anti-ganglioside IgM antibody is an anti-GM1 antibody. In certain embodiments, the anti-ganglioside IgM antibody is an anti-GM2 antibody.

[0194] In certain embodiments, the subject shows a decrease in the serum level of a cytokine after administration of a C2 inhibitor as compared to the baseline serum level of the cytokine. In certain embodiments, the cytokine is TNF-α, IFN-γ, IL-2, IL-6, IL-8, or IL-10.

[0195] In certain embodiments, the subject has been previously treated with IVIg. In certain embodiments, the subject has been previously stabilized with IVIg. In certain embodiments, the subject is dependent on IVIg.

[0196] In certain embodiments, the subject is not receiving concomitant IVIg. In certain embodiments, the subject does not require IVIg retreatment after administration of a C2 inhibitor. In certain embodiments, administration of a C2 inhibitor prolongs the time to IVIg retreatment.

[0197] In certain embodiments, the subject shows an increase in the modified Medical Research Council (mMRC) score after administration of a C2 inhibitor as compared to the baseline mMRC score of the subject. In certain embodiments, the mMRC score is the mMRC-10 total score or the mMRC-14 total score.

[0198] In certain embodiments, the subject shows an improvement in grip strength after administration of a C2 inhibitor as compared to the baseline grip strength of the subject.

[0199] In certain embodiments, the subject shows an increase in the MMN Rasch Overall Disorder Scale (MMN-RODS™) score after administration of a C2 inhibitor as compared to the baseline MMN-RODS™ score of the subject.

[0200] In certain embodiments, the C2 inhibitor is administered subcutaneously and the C2 inhibitor is administered with hyaluronidase. In certain embodiments, the C2 inhibitor is administered subcutaneously and the C2 inhibitor is co-formulated with hyaluronidase. In certain embodiments, the hyaluronidase is recombinant human hyaluronidase PH20 (rHuPH20).

[0201] In one aspect, provided herein is a C2 inhibitor for use in the treatment of multifocal motor neuropathy, wherein the treatment is carried out according to the methods disclosed herein.

[0202] In one aspect, provided herein is a C2 inhibitor for use in the manufacture of a medicament for the treatment of multifocal motor neuropathy, wherein the treatment is carried out according to the methods disclosed herein.

Examples

[0203] (Example) (Example 1 - Investigation of the Efficacy and Safety of ARGX-117 in Adults with Multifocal Motor Neuropathy (MMN)) This example describes a randomized, double-blind, placebo-controlled, parallel-group, multi-site trial (ARGX-117-2002) to evaluate the safety and tolerability, efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of the dosing regimen of ARGX-117 (a therapeutic complement inhibitor antibody targeting complement factor 2 (C2)) in adults with multifocal motor neuropathy (MMN).

[0204] Multifocal motor neuropathy (MMN) is a rare neuropathy characterized by progressive asymmetric muscle weakness and atrophy without sensory abnormalities. MMN is thought to be a chronic immune-mediated neuropathy driven by the classical complement pathway associated with the presence of autoantibodies, for example, the presence of anti-ganglioside GM1 (monosialotetrahexosylganglioside [anti-GM1]), anti-GM2 (and other gangliosides) immunoglobulin M (IgM) antibodies produced by a limited number of B cell clones. These antibodies activate the classical pathway of the complement system, which then results in the deposition of the membrane attack complex (MAC), leading to disruption of the Schwann cell-axon sheath junction, displacement of ion channel clustering, and disturbance of membrane integrity in the (para)nodal region resulting in demyelination and motor nerve conduction block.

[0205] MMN patients initially respond to intravenous immunoglobulin (IVIg), the standard treatment; however, the disease continues to progress despite treatment. The aim of the trial described in this example is to evaluate the safety and efficacy of ARGX-117 treatment in MMN patients who have previously been stabilized on IVIg.

[0206] (A. Study design) (Overall design) This is a phase 2, randomized, stratified, double-blind, placebo-controlled, parallel-group, multi-center trial of ARGX-117 in adults with MMN. The total trial duration is at least 25 weeks for all participants. The order and duration of the study periods are as follows for both cohort 1 and cohort 2: · Screening period: up to 28 days; · IVIg dependence period (IVDP) (if applicable): Only participants whose IVIg dependence is unknown at the end of the screening period enter the IVDP; · IVIg monitoring period (IVMP): The length of the IVMP is determined by the participant's IVIg administration frequency; · Double-blind treatment period (DBTP): 16 weeks; · Safety follow-up period: Participants who are not enrolled in the Long-Term Extension (LTE) study enter a 15-month safety follow-up period after completing the DBTP.

[0207] Enrollment is planned for two treatment cohorts, called Cohort 1 and Cohort 2. Data collected from the first 9 participants in Cohort 1 who complete or prematurely discontinue the 16-week DBTP are evaluated by an independent Data Monitoring Committee (IDMC). The IDMC makes a recommendation to notify the unblinded Executive Data Review Team (EDRT) to initiate enrollment in Cohort 2.

[0208] Diagnosis of MMN and IVIg dependence is evaluated by the Multicentric MMN Confirmation Committee (MCC) during the screening period. Participants with unclear IVIg dependence enter the IVDP to assess the impact of delaying IVIg administration on grip strength (GS) and / or motor function. The IDMC monitors the accumulating safety data throughout the trial.

[0209] (Screening period) The screening period is used to determine an individual's eligibility to participate in the trial. Evaluations are conducted as described in the Schedule of Activities (SoA). See Table 3.

[0210] The screening period is up to 28 days long and can be extended by an additional 14 days, with written approval from the medical monitor, for a total of 42 days. Further extensions of the screening period to align the participant's subsequent IDV1 or IMV1 with their IVIg dosing schedule do not cause screening failure.

[0211] (IVIg Dependence Period (IVDP)) The IVDP is used to determine the IVIg dependence of participants whose IVIg dependence is unclear from the explanations provided to the MCC that are summarized in the participant profile during screening.

[0212] The IVDP lasts for up to 15 weeks (105 days), depending on the IVIg administration frequency. The IVIg administration of the participants is postponed during the IVDP. The evaluation is performed at the time points described in the SoA. See Table 3.

[0213] Participants receive IVIg after a delayed dosing interval compared to their stable IVIg regimen intervals as follows: - Participants receiving IVIg every 2 weeks extend the interval to 4 weeks. - Participants receiving IVIg every 3 weeks extend the interval to 6 weeks. - Participants receiving IVIg every 4 weeks extend the interval to 8 weeks. - Participants receiving IVIg every 5 weeks extend the interval to 10 weeks.

[0214] If a participant shows a clinically significant deterioration between the scheduled visits of the IVDP, the participant receives a visit earlier than planned during the IVDP. Clinically significant deterioration is defined as a >30% decrease in GS of either hand observed for at least 2 consecutive days from the maximum post-IVIg GS after IDV1 (based on the calculation of the 3-day average) and / or a decrease of at least 2 points in the total mMRC-10 score from IDV1 to IDV2.

[0215] (IVIg Monitoring Period (IVMP)) The IVMP starts after the participant has completed the screening period and, if applicable, the IVDP, and consists of multiple IVIg dosing cycles (see Table 3).

[0216] This period establishes the baseline values for all clinical evaluation items evaluated during the DBTP. - Participants receive IVIg at the frequency, duration, and dose described in their medical history. - The IVMP includes three IVIg treatment cycles. - The length of the IVMP is determined by the individual IVIg administration frequency as follows: · Administered every 2 weeks: 35 days ·Administered every 3 weeks: 49 days ·Administered every 4 weeks: 63 days ·Administered every 5 weeks: 77 days

[0217] If participants receive IVIg over several days, the length of IVMP may be longer. Assessments are made at the time points described in Table 3. Table 3: Schedule of activities during IVIg dependence and IVIg monitoring period up to day 7

Table 3

Table 4

[0218] (Double-blind treatment period) Administration of the investigational medicinal product (IMP) is initiated at the first visit (V1) and continued throughout the entirety of the DBTP as described in the schedule of activities (SoA, Table 5). The DBTP starts 7 days after the last IVIg administration of the IVMP (i.e., V1 is 7 days after the last IVIg administration). Participants are randomly assigned to ARGX-117 or placebo at a ratio of 2:1 or 2:2:1:1 at V1 of the DBTP as discussed below. Randomization is stratified based on the individual IVIg dosing frequency.

[0219] Two dosing regimens are investigated in this study (see Table 4 below): (Cohort 1:) · Dosing regimen 1 A single dose of 30 mg / kg of ARGX-117 or placebo is administered on Day 1, followed by 4 weekly administrations of 10 mg / kg of ARGX-117 or placebo on Days 8, 15, 22, and 29 (total of 4 infusions), and 10 mg / kg of ARGX-117 or placebo is administered every 2 weeks starting on Day 43 until the end of the DBTP (total of 5 infusions). Participants are randomly assigned to ARGX-117 or placebo at a ratio of 2:1 at V1 of the DBTP. (Cohort 2:) Three options are available as the dosing regimen for cohort 2, and one of them is evaluated according to the determination of EDRT: · Option 1 (Dosing Regimen 2) Administer a single dose of 60 mg / kg of ARGX-117 or placebo on Day 1, and then administer 30 mg / kg of ARGX-117 or placebo four times a week on Days 8, 15, 22, and 29 (total of 4 infusions), and administer 30 mg / kg of ARGX-117 or placebo every two weeks starting from Day 43 until the end of DBTP (total of 5 infusions). Participants are randomly assigned to ARGX-117 or placebo in a 2:1 ratio at V1 of DBTP. · Option 2 (Dosing Regimen 3) Administer a single dose of 15 mg / kg of ARGX-117 or placebo on Day 1, and then administer 5 mg / kg of ARGX-117 or placebo four times a week on Days 8, 15, 22, and 29 (total of 4 infusions), and administer 5 mg / kg of ARGX-117 or placebo every four weeks on Days 57 and 85 until the end of DBTP (total of 2 infusions). Additionally, administer placebo every four weeks on Days 43, 71, and 99. Participants are randomly assigned to ARGX-117 or placebo in a 2:1 ratio at V1 of DBTP. · Option 3 (Dosing Regimens 2 and 3) Participants are randomly assigned to ARGX-117 (high dose / Dosing Regimen 2), ARGX-117 (low dose / Dosing Regimen 3), placebo (high dose / Dosing Regimen 2), or placebo (low dose / Dosing Regimen 3) in a 2:2:1:1 ratio at V1 of DBTP.

[0220] From the relationship between free C2 concentration and functional complement activity (CH50) after ARGX-117 administration, it is shown that a small amount of free C2 can induce a complement cascade that is reflected in CH50 activity. Therefore, different free C2 thresholds were selected to target a 99%, 98%, or 96% decrease in free C2 levels. Since the relationship between the PD effect of ARGX-117 and the clinical response (time to) in MMN patients is currently unknown, the selected dosing regimens in this study cover a wide range of PD effects from almost complete C2 and functional complement inhibition at the high-dose regimen (dosing regimen 2) to two levels of near-maximal inhibition at two low-dose regimens (dosing regimen 1 and dosing regimen 3). · Dosing regimen 1 aimed for the near-maximal PD effect of ARGX-117: a free C2 threshold of 0.4 μg / mL was selected, i.e., a mean predicted decrease in CH50 activity to approximately 35% of normal levels, along with a predicted 98% inhibition of baseline free C2 concentration (20 μg / mL). · Dosing regimen 2 (option 1; high dose) aimed for the maximal PD effect of ARGX-117: a free C2 threshold of 0.2 μg / mL, i.e., a mean predicted decrease in CH50 activity to approximately 15% of normal levels, along with a predicted 99% inhibition of baseline free C2 concentration (20 μg / mL). · Dosing regimen 3 (option 2; low dose) aimed for the near-maximal PD effect of ARGX-117: a free C2 threshold of 0.8 μg / mL, i.e., a mean predicted decrease in CH50 activity to approximately 70% of normal levels, along with a predicted 96% inhibition of baseline free C2 concentration (20 μg / mL).

[0221] For both dosing regimens, the rapid PD effect of ARGX-117 that changes the clinical response is targeted to avoid clinical deterioration and subsequent IVIg retreatment. To achieve a rapid PD effect, a dosing regimen consisting of an induction or loading phase and a subsequent maintenance phase with a lower dosing frequency has been selected. This concept of a rapid and sustained decrease in complement activity achieved by the induction or loading dose and maintained by the maintenance dose also applies to eculizumab and ravulizumab, which are C5-targeted monoclonal antibodies approved for various indications. Table 4: Study groups

Table 5

[0222] If a clinically meaningful deterioration in muscle strength and / or motor function is observed, participants are retreated with IVIg during the DBTP. Clinically meaningful deterioration is defined as a >30% decrease in grip strength (GS) of either hand (based on the calculation of the average over 3 days) and / or a decrease of at least 2 points in the total mMRC-10 score since randomization, observed continuously for at least 2 days.

[0223] The administration of the IMP is not interrupted / terminated when IVIg retreatment is initiated. Based on their clinical judgment, the principal investigator can choose not to retreat participants with IVIg in the case of a clinically meaningful deterioration. All study participants can request IVIg retreatment by the principal investigator at any time during the DBTP.

Table 6

Table 7

Table 8

[0224] (Follow-up period) The safety follow-up period characterizes the safety, PK, and PD during the washout period of ARGX-117 and includes only participants who do not roll over to LTE. The safety follow-up period begins after DBTP and is conducted over 15 months. Assessments are made at the time points described in Table 6. Table 6: Schedule of Activities during the Follow-up Period

Table 9

[0225] (Definition of study completion) A participant is considered to have completed the study when they have completed the last visit of the DBTP period and rolled over to the LTE or when they have completed the last visit of the follow-up period described in the SoA (see Table 6).

[0226] (B. Study population) (Inclusion criteria) A participant is eligible to be included in the study only if they meet all of the following criteria: 1. Be able to provide a signed informed consent including compliance with the requirements and restrictions published in the informed consent form (ICF) and this protocol. 2. Be at least 18 years old (male / female) at the time the ICF is signed. 3. Probable or definite MMN according to the EFNS / PNS 2010 guidelines at screening as confirmed by the MCC (see the clinical criteria and guidelines in Tables 7 - 10 below). 4. Have received a stable IVIg regimen prior to screening and be both of the following: a. An IVIg treatment interval of 2 - 5 weeks, and b. An IVIg dose of 0.4 - 2.0 grams per kilogram of body weight per infusion. 5. IVIg treatment dependence as confirmed by the MCC at screening or at IVIg Monitoring Visit 1 (IMV1) based on any one of the following: a. Recently initiated IVIg treatment (less than 3 months): - Clinical improvement after initiation of IVIg is recorded in the participant's medical record. b. Maintenance therapy with IVIg (for 3 months or longer) based on any one of the following: - Clinical deterioration after discontinuation of IVIg, reduction of IVIg dosage, or delay of IVIg administration within 12 months before screening (recorded in the participant's medical record), or - Clinical deterioration after delay of IVIg administration during the IVDP period. 6. Immunization with the first meningococcal vaccine, pneumococcal vaccine, and single-dose Haemophilus influenzae type B vaccine must be carried out at least 14 days before IMP administration at V1 in accordance with the country-specific immunization schedule. A documented history of vaccination against Neisseria meningitidis, Haemophilus influenzae type B, and pneumococcus is permitted. 7. The use of contraceptives by men and women should be in line with the local regulations regarding the contraceptive methods of participants in the clinical study. a. Male participants must agree not to provide sperm from the time of signing the ICF until 12 months after the last IMP administration. b. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before IMP administration can be carried out. Table 7: Clinical criteria for MMN

Table 10

Table 11

Table 12

Table 13

[0227] (Exclusion Criteria) Participants will be excluded from the study if any of the following criteria apply: 1. Any co-existing disease that may interfere with the assessment of the outcome (e.g., diabetic neuropathy, CIDP, inflammatory arthritis, or osteoarthritis affecting the hand). 2. Clinical signs or symptoms suggestive of a neuropathy other than MMN, such as a motor neuron disease (e.g., bulbar signs or hyperreflexia) or other inflammatory neuropathies (e.g., sensory neuropathy). 3. Severe mental disorders (e.g., major depression, psychosis, bipolar disorder), a history of suicide attempts, or current suicidal ideation that, in the opinion of the principal investigator of the clinical trial, may pose an excessive risk to the participant or may affect compliance with the trial protocol. 4. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infections during screening and / or IVMP. 5. Any other known autoimmune disease (e.g., SLE) that, in the opinion of the principal investigator of the clinical trial, may interfere with the accurate assessment of the clinical symptoms of MMN or may pose an excessive risk to the participant. 6. History of malignancy, except if resolved by appropriate treatment and no evidence of recurrence for more than 3 years prior to the first administration of the IMP. Participants with the following cancers are eligible: a. Appropriately treated basal cell carcinoma or squamous cell skin cancer; b. Cervical intraepithelial neoplasia; c. Breast intraepithelial neoplasia; or d. Incidental histological findings of prostate cancer (TNM stage T1a or T1b). 7. Clinical evidence of any other serious severe disease, history of recent major surgery, or any other disease that, in the opinion of the principal investigator of the clinical trial, may confound the results of the study or pose an excessive risk to the participant. 8. Pre-treatment / Concomitant therapy: a. Cyclophosphamide and / or rituximab and / or eculizumab and / or mycophenolate mofetil within 3 months prior to screening; and / or b. Use of investigational drug within 3 months before the first administration of IMP or within 5 half-lives (whichever is longer). 9. Positive for active viral infection meeting any of the following criteria in serum tests at screening: a. Hepatitis B virus (HBV) indicating acute or chronic infection; b. Hepatitis C virus (HCV) based on HCV antibody assay; or c. HIV based on test results related to the state defined as AIDS or a CD4 count of <200 cells / mm3. 10. History of alcohol, drug, or substance abuse currently or in the past (i.e., within 12 months from screening). 11. Known hypersensitivity reaction to any one of the components of IMP or its excipients. 12. Female participants with a positive serum or urine pregnancy test, lactating women, and women intending to become pregnant during the study or within 15 months after the last administration of IMP. 13. ALT or AST more than twice the upper limit of normal, total bilirubin more than 1.5 times the upper limit of normal in the reference range of the central laboratory, or any other clinically significant laboratory finding abnormality. 14. Estimated glomerular filtration rate of 60 mL / min / 1.73 m2 or less calculated by the central laboratory using the Modification of Diet in the Renal - Disease formula for 4 - variable kidney disease.

[0228] (C. Study Evaluation and Procedures) The test procedures and their timing are summarized in the "Activity Schedule" of Tables 3, 5, and 6 above.

[0229] For calculation of changes from baseline, the last value collected before the first administration of IMP is used as the baseline.

[0230] (Efficacy Evaluation) Efficacy evaluation is performed before the administration of IMP and IVIg and in the following preferred order: · GS · mMRC - 14 total score ·Outcome measures reported by participants, including MMN-RODS (copyright), EQ-5D-5L, CAP-PRI, PGIC, FSS, HRPQ, and TSQM ·9-HPT It is preferably carried out.

[0231] When IVIg and IMP are administered on the same day, it is preferable that IMP be administered before IVIg.

[0232] (Time to retreatment with IVIg) The criteria for retreatment with IVIg are defined based on a clinical deterioration of at least a 30% decrease in either GS (based on the calculation of the average over 3 days) observed continuously for at least 2 days and / or a decrease of at least 2 points in the total mMRC-10 score compared to the day of randomization. Both GS and the total mMRC-10 score are standard and clinically meaningful means used to measure clinical efficacy in clinical trials of MMN. By using these measures as the criteria for retreatment with IVIg, the time to retreatment is thus directly associated with a clinically meaningful outcome. Both outcomes are evaluated individually as secondary endpoints to support the results of the evaluation item of the time to IVIg retreatment. The threshold for each deterioration is set to represent a clinically significant decrease in disease activity.

[0233] The time at which a participant reaches this threshold is considered the time to recurrence. The date and time of administration of IVIg retreatment are considered the time to retreatment with IVIg. Both the time to recurrence and the time to retreatment with IVIg are recorded.

[0234] All study participants can request IVIg retreatment by the treating physician at any time during DBTP. The treating physician will contact the medical monitor if the participant requests IVIg retreatment but does not meet the criteria for clinically significant deterioration.

[0235] (Total mMRC-14 and mMRC-10 scores) The mMRC total score assesses the strength / weakness of movements of pre-determined muscle groups (upper and lower limbs). Participants are recommended to be scored for the mMRC total score by the same assessor during the test visit.

[0236] The scoring system for the mMRC total score and the muscle groups examined for each mMRC total score are provided in Table 11 and Table 12, respectively. Table 11: Scoring of mMRC total score

Table 14

Table 15

[0237] (Grip strength) Martin - type hand dynamometers are used for the measurement of daily grip strength during the screening period, IVDP (if applicable), IVMP, and DBTP, respectively. During these periods, grip strength is measured daily in a standardized manner.

[0238] Daily grip strength measurements consist of three repeated contractions with maximum effort by the participant. The duration of each contraction is 3 seconds. Each examination is recommended to start with the participant gripping with the right hand and then with the left hand. The examination is performed in the following recommended order: three repetitions are performed continuously with the right hand, and then three repetitions are performed with the left hand. There is a 30 - second rest period between each of the three repetitions, and a 2 - minute rest period between each hand.

[0239] Participants perform all grip strength tests sitting: Participants sit comfortably in a chair without armrests, place both feet flat on the floor, sink their buttocks as deeply as possible into the chair, and position their hips and knees at approximately 90°. Rotate the shoulder of the limb being tested medially and neutrally, flex the elbow to 90°, keep the forearm in a neutral position, and position the wrist at a dorsiflexion of 0° - 30° and a ulnar flexion of 0° - 15°. Participants are instructed to maintain these positions during the grip strength test.

[0240] Measurements are evaluated and reported by the investigator during the on-site test visit. It is recommended that participants be evaluated by the same evaluator during the on-site visit. Grip strength is measured daily by the participants throughout the IVDP, IVMP, and DBTP. When performed by the participants, the date, time, and results are recorded electronically.

[0241] It is recommended that measurements be taken at the same time of day (preferably in the morning) for each assessment.

[0242] The measured values of the left hand GS for 3 days and the measured values of the right hand GS for 3 days are recorded respectively, and the 1-day averages of the left and right hands are calculated. Based on the averages obtained for each hand, a 3-day moving average is determined. The 1-day moving average consists of the -2nd day, -1st day, and 0th day.

[0243] (Rasch-built Overall Disability Scale (RODS)) The MMN-RODS (copyright) is a disease-specific PRO tool specifically constructed to capture the activity limitations of MMN patients. It is scored for each item as 0 (not able to perform), 1 (able to perform with difficulty), or 2 (able to perform without difficulty), and consists of 25 items with a total score of 0 - 50. The 25-item MMN-RODS (copyright) is provided in Table 13. Table 13: 25-item Rasch-built Overall Disability Scale for MMN (MMN-RODS (copyright))

Table 16

[0244] (Nine-hole peg test) The 9-HPT is a quantitative measurement tool for upper limb (arm and hand) function. Both the dominant and non-dominant hands are examined twice (the dominant hand is tested twice in succession, and immediately afterwards, the non-dominant hand is tested twice in succession). To exclude training effects, all participants should receive training when evaluating the 9-HPT before the start of the test. It is recommended that participants be evaluated by the same assessor during the on-site visit.

[0245] (EuroQol 5-Dimension 5-Level) Quality of life is evaluated by the EQ-5D-5L, which enables response recording based on five levels of severity. This is a standardized tool for use as a health measure for clinical and economic evaluations. The descriptive system includes five dimensions: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. Each dimension score includes five levels: no problems, mild problems, moderate problems, severe problems, and extreme problems. Participants rate their health state from 0 (the worst imaginable health) to 100 (the best imaginable health).

[0246] (Chronic Acquired Polyneuropathy Patient Report Index) Next to general QOL, disease-specific QOL is evaluated by the CAP-PRI. This tool includes a 15-item assessment. The items are scored 0 (none), 1 (a little), or 2 (a lot), and a total score in the range of 0-30 is obtained.

[0247] (Patient Global Impression of Change) The PGIC is a patient-reported outcome, which was published by the National Institute of Mental Health in 1976. The self-report scale PGIC reflects the patient's beliefs about the effectiveness of treatment. The PGIC is a 7-point scale indicating the patient's assessment of overall improvement.

[0248] (Fatigue Severity Scale) The FSS is a 9-item self-report questionnaire scale developed in 1989 and designed to distinguish between fatigue and clinical depression since they share some of the same symptoms. The FSS consists of having participants rate their level of fatigue over 9 items according to how well they feel the description applied to themselves in the previous week and asking them to rate on a scale of 1 - 7, answering a short questionnaire. A low value indicates that the description is not very appropriate, while a high value indicates agreement. Scoring is done by calculating the average response to the questions (adding up all the answers and dividing by 9).

[0249] (Health-Related Productivity Questionnaire) The HRPQ was originally developed in Parkinson's disease patients to provide data on lost time at work or educational activities and decreased effectiveness in work attempts. These criteria form an important part of work-related productivity and are used in this study to evaluate health-related and work-related productivity.

[0250] (14-Item Questionnaire on Drug Therapy) The original version (version 1.4) of the TSQM questionnaire was developed in 2004 to measure patients' satisfaction with drug therapy using 4 scales (side effects, effectiveness, convenience, and overall satisfaction) and is used in this study.

[0251] (D. Pharmacokinetics) The concentration of ARGX-117 in serum is determined using a validated enzyme-linked immunosorbent assay. The concentration is calculated by interpolation from a calibration curve. Quality control samples are analyzed throughout the test. Their measured concentrations are used to determine the overall precision between assays and the accuracy of the analysis.

[0252] The serum PK parameters of ARGX-117 are derived by non-compartmental analysis of serum concentration-time profiles using the actual collection times. The PK parameters, definitions, and calculation methods are as follows: AUC 0-t AUC from time 0 to time t of the last measurable concentration calculated using the linear up-log down trapezoidal method AUC 0-xh AUC from time 0 to x hours after IMP administration calculated using the linear up-log down trapezoidal method AUC ∞ AUC 0-t +(C t / λ z )(where C t is the last observed measurable concentration and λ z is the terminal elimination rate constant) to calculate AUC from time 0 to infinity C max Observed maximum serum concentration C xh Concentration x hours after dosing t max Time to reach Cmax t 1 / 2 Apparent terminal half-life V z (Apparent) volume of distribution ( / F) C L (Apparent) total clearance ( / F)

[0253] C max Dose-normalized parameters including C / dose and AUC / dose are evaluated.

[0254] (E. Pharmacodynamics) Blood samples are collected for determination of free C2 concentration, total C2 concentration, and functional complement activity (CH50) as indicated in the evaluation schedule. Visits 2 (Day 4), 10 (Day 78), and 13 (Day 102) are not mandatory and are considered optional. The goal is for a minimum of 14 participants per cohort to participate in any of the optional visits.

[0255] Blood is collected following the standard procedures of a specialized laboratory. Further details regarding information on the equipment and procedures during sample collection are documented in the individual laboratory manuals.

[0256] These PD markers are determined using assays that are validated for their intended use.

[0257] (F. Genetics) Blood samples for DNA isolation are collected from participants who have consented to participate in the genetic analysis component of the study. Participation is voluntary. Participants who do not wish to participate in the genetic study can still participate in the trial.

[0258] DNA is isolated from blood samples for single nucleotide polymorphism (SNP) analysis, including complement regulatory proteins. Samples are collected according to the schedule described in the SoA.

[0259] (G. Biomarkers) Blood samples are collected to evaluate the effect of ARGX-117 treatment on components of the complement cascade. Biomarkers include C1q, C3, C4, and C5. Samples are collected according to the schedule described in the SoA.

[0260] (H. Exploratory Assessment Items) The following exploratory assessment items are reported in the clinical trial report. Blood samples for cytokine measurement are collected. At a minimum, the following cytokines: TNF-α, IFN-γ, IL-2, IL-6, IL-8, and IL-10 are evaluated. Blood samples for biomarkers are collected to evaluate the effect of ARGX-117 treatment on components of the complement cascade.

[0261] The following exploratory assessment items are reported separately from the main clinical trial report. Blood samples are collected to evaluate the effect of ARGX-117 on NfL, a marker of neurological injury.

[0262] Blood samples are collected to evaluate the effect of ARGX-117 treatment on the titers of autoantibodies against gangliosides including, but not limited to, anti-GM1 and anti-GM2.

[0263] Blood samples are also collected for SNP analysis.

[0264] Study samples are also collected; additional markers may be measured in samples stored for future analysis.

[0265] Trial sponsors can store the samples for up to 15 years after the end of the trial. Further, with the consent of the participants, the samples can be used for further research by the trial sponsor or other parties, such as universities or other companies, to address any scientific questions related to the development of ARGX-117, complement biology, MMN, or other diseases, related or new treatments, or research methods. Further, the blood samples can be used to validate the methods used to measure ARGX-117, antibodies, and biomarkers.

[0266] (I. Immunogenicity assessment) (Assessment of anti-ARGX-117 antibodies) Blood samples are collected at the time points specified in the activity schedule to evaluate the serum levels of ADA against ARGX-117. These samples are examined by the trial sponsor or a designated agent of the trial sponsor.

[0267] Serum samples are screened and confirmed for ADA against ARGX-117, and the titers of samples confirmed as positive are reported. Other assays may be performed to further characterize the immunogenicity of ARGX-117.

[0268] Samples may be stored for up to 15 years (or in accordance with local regulations) after the last study visit of the last participant at a facility selected by the trial sponsor to enable further analysis of the immune response against ARGX-117.

[0269] (Anti-ARGX-117 neutralizing antibody) Neutralizing antibodies against ARGX-117 are evaluated in the collected serum samples and can be retained from all participants according to the schedule of activities.

[0270] Samples are stored for up to 15 years (or according to local regulations) at a facility selected by the sponsor of the clinical trial, after the last study visit of the last participant, to enable further analysis of the immune response to ARGX-117 for future use. (J. Objectives and evaluation items) Table 14: Objectives and evaluation items

Table 17

[0271] To determine the efficacy of ARGX-117 compared to placebo in adult participants with MMN previously stabilized with IVIg, the median time to the first retreatment with IVIg is estimated separately for each treatment group using the Kaplan-Meier product-limit method, and a comparison between treatment groups is performed using the stratified log-rank test. Participants who discontinue the study for any reason or who complete DBTP before retreatment with IVIg are censored at the last visit on the date of contact.

[0272] A sensitivity analysis is also performed for the time to relapse. The time to relapse is defined as the time until the participant reaches the threshold of clinical deterioration.

[0273] To correct for differences in the duration of the study, evaluation items based on AUC are standardized to the mean AUC per week (7 days).

[0274] For continuous evaluation items, an ANCOVA model that includes the treatment factor, stratification variables, and baseline (mMRC-10 score or GS) as covariates is used. For proportions, a stratified Cochran-Mantel-Haenszel test that controls for the stratification variables is used. (Incorporation by reference) All patents and non-patent references cited above are hereby incorporated by reference in their entirety into this specification.

Claims

**Claim 1** A method for treating multifocal motor neuropathy (MMN) in a subject in need thereof, the method comprising administering to the subject an effective amount of a complement component 2 (C2) inhibitor. **Claim 2** The method according to claim 1, wherein the C2 inhibitor is administered at a dose of 0.1 mg / kg to 100 mg / kg. **Claim 3** The method according to claim 1 or 2, wherein the C2 inhibitor is administered at a dose of 5 mg / kg to 60 mg / kg. **Claim 4** The method according to any one of claims 1 to 3, wherein the C2 inhibitor is administered at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg. **Claim 5** The method according to any one of claims 1 to 4, wherein the C2 inhibitor is administered at a dose of 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, or 60 mg / kg. **Claim 6** The method according to claim 1, wherein the C2 inhibitor is administered at a fixed dose of 500 mg to 1500 mg. **Claim 7** The method according to claim 6, wherein the C2 inhibitor is administered at a fixed dose of 1200 mg. **Claim 8** The method according to any one of claims 1 to 7, wherein the C2 inhibitor is administered intravenously. **Claim 9** The method according to any one of claims 1 to 7, wherein the C2 inhibitor is administered subcutaneously. **Claim 10** The method according to any one of claims 1 to 9, wherein the C2 inhibitor is administered once a week. **Claim 11** The method according to any one of claims 1 to 9, wherein the C2 inhibitor is administered once every two weeks. **Claim 12** The method according to any one of claims 1 to 9, wherein the C2 inhibitor is administered once every four weeks. **Claim 13** The method according to any one of claims 1 to 9, wherein the C2 inhibitor is administered once every eight weeks. **Claim 14** The method according to any one of claims 1 to 9, wherein the C2 inhibitor is administered at a dose of 5 mg / kg once a week, once every two weeks, or once every four weeks. **Claim 15** The method according to any one of claims 1 to 9, wherein the C2 inhibitor is administered at a dose of 10 mg / kg once a week, once every two weeks, or once every four weeks. **Claim 16** The method according to any one of claims 1 to 9, wherein the C2 inhibitor is administered at a dose of 15 mg / kg once a week, once every two weeks, or once every four weeks. **Claim 17** The method according to any one of claims 1 to 9, wherein the C2 inhibitor is administered once a week, once every two weeks, or once every four weeks at a dose of 30 mg / kg.

18. The method according to any one of claims 1 to 9, wherein the C2 inhibitor is administered once a week, once every two weeks, or once every four weeks at a dose of 60 mg / kg.

19. The method according to any one of claims 1 to 18, wherein the C2 inhibitor is administered according to a loading regimen that reduces the level of free C2 in the blood of the subject to or below a threshold level.

20. The method according to claim 19, further comprising a maintenance regimen after the loading regimen, wherein the maintenance regimen comprises administering the C2 inhibitor according to a regimen that maintains the level of free C2 in the blood of the subject at or below the threshold level.

21. The method according to claim 19 or 20, wherein the threshold level is 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, or 0.8 μg / mL.

22. The method according to claim 19 or 20, wherein the threshold level is 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20% of the baseline level of free C2 of the subject.

23. The method according to any one of claims 19 to 22, wherein the loading regimen is a single initial dose and one or more subsequent doses thereafter.

24. The method according to claim 23, wherein each of the one or more subsequent doses is an amount less than the single initial dose.

25. The method according to claim 23 or 24, wherein 1, 2, 3, 4, 5, or 6 subsequent doses follow the single initial dose.

26. The method according to any one of claims 23 to 25, wherein the subsequent doses are administered once a week or once every two weeks.

27. The method according to any one of claims 23 to 26, wherein 4 subsequent doses follow the single initial dose, and the subsequent doses are administered once a week.

28. The method according to any one of claims 23 to 27, wherein the first subsequent dose is administered one week after the single initial dose.

29. The method according to any one of claims 23 to 28, wherein the single initial dose is 0.1 mg / kg to 100 mg / kg.

30. The method according to any one of claims 23 to 28, wherein the single initial dose is 10 mg / kg to 60 mg / kg.

31. The method according to claim 30, wherein the single initial dose is 15 mg / kg.

32. The method according to claim 30, wherein the single initial dose is 30 mg / kg.

33. The method according to claim 30, wherein the single initial dose is 60 mg / kg.

34. The method according to any one of claims 23 to 28, wherein the single initial dose is a fixed dose of 500 mg to 1500 mg.

35. The method according to claim 34, wherein the single initial dose is a fixed dose of 1200 mg.

36. The method according to any one of claims 23 to 35, wherein each of the subsequent doses is 0.1 mg / kg to 100 mg / kg.

37. The method according to any one of claims 23 to 35, wherein each of the subsequent doses is 5 mg / kg to 60 mg / kg.

38. The method according to claim 37, wherein each of the subsequent doses is 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg.

39. The method according to claim 38, wherein each of the subsequent doses is 5 mg / kg.

40. The method according to claim 38, wherein each of the subsequent doses is 10 mg / kg.

41. The method according to claim 38, wherein each of the subsequent doses is 30 mg / kg.

42. The method according to any one of claims 23 to 35, wherein each of the subsequent doses is a fixed dose of 500 mg to 1500 mg.

43. The method according to claim 42, wherein each of the subsequent doses is a fixed dose of 1200 mg.

44. The method according to any one of claims 23 to 31, wherein the single initial dose is 15 mg / kg and each of the subsequent doses is 5 mg / kg.

45. The method according to any one of claims 23 to 31, wherein the single initial dose is 30 mg / kg and each of the subsequent doses is 10 mg / kg.

46. The method according to any one of claims 23 to 31, wherein the single initial dose is 60 mg / kg and each of the subsequent doses is 30 mg / kg.

47. The method according to any one of claims 19 to 46, wherein the loading regimen is administered intravenously.

48. The method according to any one of claims 19 to 46, wherein the loading regimen is administered subcutaneously.

49. The method according to any one of claims 19 to 48, wherein the loading regimen reduces the level of free C2 to or below the threshold level in 1, 2, 3, 4, 5, 6, or 7 days.

50. The method according to any one of claims 19 to 48, wherein the loading regimen reduces the level of free C2 to or below the threshold level in 1, 2, 3, 4, or 5 weeks.

51. The method according to any one of claims 20 to 50, wherein the maintenance regimen is administered once a week, once every two weeks, once every three weeks, once every four weeks, once every five weeks, once every six weeks, once every seven weeks, or once every eight weeks, at a dose of 0.1 to 100 mg / kg.

52. The method according to any one of claims 20 to 51, wherein the maintenance regimen is administered once a week at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg.

53. The method according to any one of claims 20 to 51, wherein the maintenance regimen is administered once every two weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg.

54. The method according to claim 53, wherein the maintenance regimen is administered once every two weeks at a dose of 10 mg / kg.

55. The method according to claim 53, wherein the maintenance regimen is administered once every two weeks at a dose of 30 mg / kg.

56. The method according to any one of claims 20 to 51, wherein the maintenance regimen is administered once every three weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg.

57. The method according to any one of claims 20 to 51, wherein the maintenance regimen is administered once every four weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg.

58. The method according to claim 57, wherein the maintenance regimen is administered once every four weeks at a dose of 5 mg / kg.

59. The method according to any one of claims 20 to 51, wherein the maintenance regimen is administered once every 5 weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg.

60. The method according to any one of claims 20 to 51, wherein the maintenance regimen is administered once every 6 weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg.

61. The method according to any one of claims 20 to 51, wherein the maintenance regimen is administered once every 7 weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg.

62. The method according to any one of claims 20 to 51, wherein the maintenance regimen is administered once every 8 weeks at a dose of 0.1 mg / kg, 0.5 mg / kg, 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg, 30 mg / kg, 60 mg / kg, or 80 mg / kg.

63. The method according to any one of claims 20 to 51, wherein the maintenance regimen is administered once every 1, 2, 3, 4, 5, 6, 7, or 8 weeks at a dose of 500 mg to 1500 mg.

64. The method according to claim 63, wherein each of the subsequent doses is a fixed dose of 1200 mg.

65. The method according to any one of claims 20 to 64, wherein the maintenance regimen is administered 1, 2, 3, 4, 5, 6, 7, or 8 weeks after the loading regimen.

66. The method according to any one of claims 20 to 65, wherein the maintenance regimen is administered when the level of free C2 in the blood of the subject exceeds a threshold level.

67. The method according to any one of claims 20 to 66, wherein the maintenance regimen is administered intravenously.

68. The method according to any one of claims 20 to 66, wherein the maintenance regimen is administered subcutaneously.

69. The loading regimen is a single initial dose of 15 mg / kg; and four subsequent doses of 5 mg / kg each, administered once a week, starting 1 week after the single initial dose : and wherein the maintenance regimen is a dose of 5 mg / kg administered once every four weeks : The method according to claim 20.

70. wherein the loading regimen is a single initial dose of 30 mg / kg; and four subsequent doses of 10 mg / kg each, administered once a week, starting one week after the single initial dose ; and wherein the maintenance regimen is a dose of 10 mg / kg administered once every two weeks : The method according to claim 20.

71. wherein the loading regimen is a single initial dose of 60 mg / kg; and four subsequent doses of 30 mg / kg each, administered once a week, starting one week after the single initial dose ; and wherein the maintenance regimen is a dose of 30 mg / kg administered once every two weeks : The method according to claim 20.

72. The method according to any one of claims 69 to 71, wherein the maintenance regimen starts one week after the last subsequent dose of the loading regimen.

73. The method according to any one of claims 69 to 71, wherein the maintenance regimen starts two weeks after the last subsequent dose of the loading regimen.

74. The method according to any one of claims 20 to 73, wherein the loading regimen is administered intravenously and the maintenance regimen is administered subcutaneously.

75. The method according to any one of claims 20 to 73, wherein the loading regimen is administered subcutaneously and the maintenance regimen is administered intravenously.

76. The method according to any one of claims 20 to 73, wherein both the loading regimen and the maintenance regimen are administered intravenously.

77. The method according to any one of claims 20 to 73, wherein both the loading regimen and the maintenance regimen are administered subcutaneously.

78. The method according to any one of claims 1 to 77, wherein the motility of the subject is improved as compared to the motility of the subject achieved with standard treatment using intravenous immunoglobulin (IVIg) and / or the sensory symptoms of the subject.

79. The method according to any one of claims 1 to 78, wherein the subject shows a decrease in the level of free C2 in the subject's blood after administration of the C2 inhibitor as compared to the baseline level of free C2 in the subject's blood.

80. The method of claim 79, wherein the level of free C2 in the blood of the subject is reduced by at least about 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% as compared to the baseline level of free C2 in the blood of the subject.

81. The method according to any one of claims 1 to 80, further comprising administering an additional therapeutic agent to the subject.

82. The method of claim 81, wherein the additional therapeutic agent is IVIg.

83. The method of claim 81, wherein the additional therapeutic agent is rituximab, eculizumab, cyclophosphamide, or mycophenolate mofetil.

84. The method of claim 82, wherein the IVIg is administered to the subject once every two weeks, once every three weeks, once every four weeks, or once every five weeks.

85. The method according to any one of claims 1 to 84, wherein the subject has a detectable baseline serum level of anti-ganglioside IgM antibody.

86. The method according to any one of claims 1 to 85, wherein the subject has been previously treated with IVIg.

87. The method according to any one of claims 1 to 86, wherein the subject has been previously stabilized with IVIg.

88. The method according to any one of claims 1 to 87, wherein the subject is dependent on IVIg.

89. The method according to any one of claims 1 to 81, wherein the subject is not receiving concomitant IVIg.

90. The method of claim 89, wherein the subject does not require IVIg retreatment after administration of the C2 inhibitor.

91. The method according to any one of claims 1 to 89, wherein the administration of the C2 inhibitor prolongs the time to IVIg retreatment.

92. The method according to any one of claims 1 to 91, wherein the subject shows an increase in the modified Medical Research Council (mMRC) score after administration of the C2 inhibitor as compared to the subject's baseline mMRC score.

93. The method of claim 92, wherein the mMRC score is the mMRC-10 total score or the mMRC-14 total score.

94. The method according to any one of claims 1 to 93, wherein the subject shows an improvement in grip strength after administration of the C2 inhibitor as compared to the subject's baseline grip strength.

95. The method according to any one of claims 1 to 94, wherein the subject shows an increase in the MMN Rasch Overall Disorder Scale (MMN-RODS) score after administration of the C2 inhibitor as compared to the baseline MMN-RODS score of the subject.

96. The method according to any one of claims 1 to 95, wherein the C2 inhibitor is an antibody that specifically binds to C2.

97. The method according to any one of claims 1 to 96, wherein the C2 inhibitor is an antibody that specifically binds to C2b.

98. The method according to claim 96 or claim 97, wherein the antibody comprises a heavy chain variable region (VH) comprising the CDRH1, CDRH2, and CDRH3 amino acid sequences of the VH amino acid sequence shown in SEQ ID NO: 7, or a variant thereof comprising 1 to 5 amino acid changes in any one of the CDRH1, CDRH2, or CDRH3 amino acid sequences; and / or a light chain variable region (VL) comprising the CDRL1, CDRL2, and CDRL3 amino acid sequences of the VL amino acid sequence shown in SEQ ID NO: 8, or a variant thereof comprising 1 to 5 amino acid changes in any one of the CDRL1, CDRL2, or CDRL3 amino acid sequences.

99. (a) The VH each comprises SEQ ID NO: 1, or a variant thereof comprising 1 to 5 amino acid changes, SEQ ID NO: 2, or a variant thereof comprising 1 to 5 amino acid changes, and SEQ ID NO: 3, or a variant thereof comprising 1 to 5 amino acid changes in the CDRH1, CDRH2, and CDRH3 amino acid sequences; and / or (b) The VL each comprises SEQ ID NO: 4, or a variant thereof comprising 1 to 5 amino acid changes, SEQ ID NO: 5, or a variant thereof comprising 1 to 5 amino acid changes, and SEQ ID NO: 6, or a variant thereof comprising 1 to 5 amino acid changes in the CDRL1, CDRL2, and CDRL3 amino acid sequences, The method according to claim 96 or claim 97.

100. The method according to claim 99, wherein the antibody comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, and 6, respectively.

101. The method according to any one of claims 96 to 100, wherein the antibody comprises a VH comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence shown in SEQ ID NO: 7; and / or a VL comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence shown in SEQ ID NO:

8.

102. The method according to claim 96 or claim 97, wherein the antibody comprises a VH comprising the amino acid sequence shown in SEQ ID NO: 7 and a VL comprising the amino acid sequence shown in SEQ ID NO:

8.

103. The method according to any one of claims 96 to 102, wherein the antibody comprises a heavy chain comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence shown in SEQ ID NO: 9 and / or a light chain comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence shown in SEQ ID NO:

10.

104. The method according to any one of claims 96 to 102, wherein the antibody comprises a heavy chain comprising the amino acid sequence shown in SEQ ID NO: 9 and a light chain comprising the amino acid sequence shown in SEQ ID NO:

10.

105. A C2 inhibitor for use in the treatment of multifocal motor neuropathy, wherein the treatment is carried out according to the method according to any one of claims 1 to 104, said C2 inhibitor.

106. A C2 inhibitor for use in the manufacture of a medicament for the treatment of multifocal motor neuropathy, wherein the treatment is carried out according to the method according to any one of claims 1 to 105, said C2 inhibitor.

107. Use of a C2 inhibitor for the treatment of multifocal motor neuropathy, wherein the treatment is carried out according to the method according to any one of claims 1 to 106, said use.

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