Treatment method for chronic inflammatory demyelinating polyneuropathy using anti-FcRN antibody

Abstract

The present disclosure relates to methods of treating CIDP with anti-FcRn antibodies.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 63 / 374,644, filed September 6, 2022, which is incorporated herein by reference in its entirety.

[0002] Incorporating an array list by reference The Sequence Listing associated with this application has been provided electronically in XML file format and is incorporated herein by reference. The name of the XML file containing the Sequence Listing is "MUNO-011_01WO_ST26." The XML file is 66,055 bytes in size and was created and electronically submitted on August 18, 2023.

[0003] Field The present disclosure relates to methods of treating chronic inflammatory demyelinating polyneuropathy using anti-FcRn antibodies. [Background technology]

[0004] Chronic inflammatory demyelinating polyneuropathy (CIDP) affects approximately 16,000 patients in the United States, with 70% of these patients requiring ongoing treatment. CIDP is characterized by primary demyelination of motor and sensory nerves. The cause of CIDP is unknown, but a growing body of evidence suggests that the disease is immunologically mediated (Mathey et al., J Urnal f Neur l Gy, Neur Surgery & Psychiatry 2015; W lbert et al., JCI Insight. 2020 Feb 13;5(3):e132411. d i: 10.1172 / jci.insight.132411). Multiple immune mechanisms, including cellular (macrophage), humoral, and complement systems, are involved in the pathogenesis of CIDP (K·ike H et al., Neurol Ther. 2020 Dec;9(2):213-227; Quer·l et al., Neurotherapeutics. 2022 Apr).

[0005] While no autoantibodies are identified in 50-60% of CIDP patients, anti-myelin peripheral nerve IgG is detected in 30-40% of patients (Mathey et al.).As mentioned above, the pathogenesis of CIDP involves multiple immune mechanisms, including cellular (macrophage), humoral, and complement systems (Mathey et al., K·ike et al.).

[0006] CIDP is a long-term, chronic condition for many patients, often requiring ongoing treatment. However, traditional CIDP treatments can cause side effects and present logistical challenges. Therefore, there remains an unmet need for easily administered, effective treatments.

[0007] Antibodies are immunological proteins that bind to specific antigens. In most animals, including humans and mice, antibodies are composed of paired heavy and light polypeptide chains, each of which has two distinct regions, called variable and constant regions. The variable regions of the heavy and light chains exhibit high sequence diversity among antibodies and are responsible for binding to target antigens. The constant regions, which exhibit less sequence diversity, are responsible for binding to other natural proteins to induce various biochemical events.

[0008] Under normal conditions, the average serum half-life of most IgGs (i.e., IgG1, IgG2, and IgG4, except for the IgG3 isotype) is approximately 21 days in humans (M·rell et al. Invest. 49(4):673-80, 1970). This is a long period compared to the serum half-lives of other plasma proteins. In relation to the long serum half-life of IgG, IgG taken up into cells by endocytosis (endo·cyt·sis) tightly binds to the neonatal Fc receptor (FcRn) in endosomes at pH 6.0, allowing it to avoid the degradative lysosomal pathway. (FcRn is a type of Fcγ receptor, also known as FcRP, FcRB, or Brambell receptor.) When the IgG-FcRn complex circulates at the plasma membrane, IgG rapidly dissociates from FcRn at the slightly basic pH (~7.4) of the bloodstream. Through this receptor-mediated recycling mechanism, FcRn effectively prevents IgG from lysosomal degradation and extends the half-life of IgG (R··penian et al., J. Immun·l. 170:3528, 2003).

[0009] FcRn is a noncovalent heterodimer generally present in the endosomes of endothelial and epithelial cells. It is a membrane-bound receptor with three heavy chain α domains (α1, α2, and α3) and a single soluble light chain β2-microglobulin (β2m) domain. Structurally, it belongs to the major histocompatibility complex class 1 molecule family, which shares the β2m light chain. The molecular weight of the FcRn chain is approximately 46 kDa and consists of an ectodomain containing the α1, α2, and α3 heavy chain domains and the β2m light chain domain, a single carbohydrate chain, a single transmembrane region, and a relatively short cytoplasmic domain. Summary of the Invention [Problem to be solved by the invention]

[0010] Provided herein is a method for treating CIDP, comprising administering a first therapeutically effective amount of an anti-FcRn antibody or its antigen-binding fragment to a patient in need of treatment for chronic inflammatory demyelinating polyneuropathy. wherein the antibody or antigen-binding fragment comprises: (a) a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence set forth in SEQ ID N·:27, an HCDR2 comprising the amino acid sequence set forth in SEQ ID N·:28, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID N·:29; and (b) a light chain variable region comprising an LCDR1 comprising the amino acid sequence set forth in SEQ ID N·:30, an LCDR2 comprising the amino acid sequence set forth in SEQ ID N·:31, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID N·:32; or (b) a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence set forth in SEQ ID N·:49, an HCDR2 comprising the amino acid sequence set forth in SEQ ID N·:22, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID N·:23; and a light chain variable region comprising an LCDR1 comprising the amino acid sequence set forth in SEQ ID N·:50, an LCDR2 comprising the amino acid sequence set forth in SEQ ID N·:25, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID N·:26. [Means for solving the problem]

[0011] In some embodiments, the antibody or antigen-binding fragment comprises (a) a heavy chain variable region comprising an amino acid sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N·:6, and a light chain variable region comprising an amino acid sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N·:16, or (b) a heavy chain variable region comprising an amino acid sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N·:51, and a light chain variable region comprising an amino acid sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N·:52. In some embodiments, the antibody or antigen-binding fragment comprises (a) a heavy chain variable region comprising the sequence set forth in SEQ ID N·:6 and a light chain variable region comprising the sequence set forth in SEQ ID N·:16, or (b) a heavy chain variable region comprising the sequence set forth in SEQ ID N·:51 and a light chain variable region comprising the sequence set forth in SEQ ID N·:52.

[0012] In some embodiments, the antibody or antigen-binding fragment binds to FcRn with a KD (dissociation constant) of 0.01 nM to 2 nM at pH 6.0 or pH 7.4, In some embodiments, the KD is measured by surface plasmon resonance (SPR).

[0013] In some embodiments, the antibody or antigen-binding fragment is administered subcutaneously. In some embodiments, the antibody or antigen-binding fragment is administered once a week.

[0014] In some embodiments, the first therapeutically effective amount of the antibody or antigen-binding fragment is 300 mg to 500 mg. In some embodiments, the first therapeutically effective amount of the antibody or antigen-binding fragment is 340 mg. In some embodiments, the first therapeutically effective amount of the antibody or antigen-binding fragment is 500 mg to 700 mg. In some embodiments, the first therapeutically effective amount of the antibody or antigen-binding fragment is 680 mg. In some embodiments, the first therapeutically effective amount of the antibody or antigen-binding fragment is administered for 12 weeks. In some embodiments, the first therapeutically effective amount of the antibody or antigen-binding fragment is administered for at least 4 weeks or at least 12 weeks. In some embodiments, the antibody or antigen-binding fragment is administered subcutaneously once weekly.

[0015] In some embodiments, the method further comprises administering to the subject a second therapeutically effective dose of the antibody or antigen-binding fragment. In some embodiments, the second therapeutically effective dose is 340 mg. In some embodiments, the second therapeutically effective dose of the antibody or antigen-binding fragment is administered for 12 weeks. In some embodiments, the first therapeutically effective dose of the antibody or antigen-binding fragment is administered for at least 4 weeks or at least 12 weeks. In some embodiments, the antibody or antigen-binding fragment is administered subcutaneously once a week.

[0016] In some embodiments, the method further comprises administering to the patient a third therapeutically effective amount of the antibody or antigen-binding fragment. In some embodiments, the third therapeutically effective amount is 340 mg. In some embodiments, the third therapeutically effective amount is 680 mg. In some embodiments, the third therapeutically effective amount is administered for at least 4 weeks, at least 12 weeks, or at least 28 weeks. In some embodiments, the third therapeutically effective amount is administered for 28 weeks. In some embodiments, the antibody or antigen-binding fragment is administered subcutaneously once a week.

[0017] In some embodiments, patients who do not relapse during administration of the second therapeutically effective dose are administered 340 mg of the antibody or antigen-binding fragment. In some embodiments, patients who relapse during administration of the second therapeutically effective dose are administered 680 mg of the antibody or antigen-binding fragment (e.g., for at least 4 weeks), followed by 340 mg of the antibody or antigen-binding fragment. In some embodiments, the antibody or antigen-binding fragment is administered subcutaneously once weekly. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered with at least one additional therapeutic agent.

[0018] In another aspect, provided herein is a method for treating chronic inflammatory demyelinating polyneuropathy, comprising administering to a patient in need of treatment thereof a first therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment thereof. wherein the antibody or antigen-binding fragment: (a) a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence set forth in SEQ ID N·:27, an HCDR2 comprising the amino acid sequence set forth in SEQ ID N·:28, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID N·:29, and a light chain variable region comprising an LCDR1 comprising the amino acid sequence set forth in SEQ ID N·:30, an LCDR2 comprising the amino acid sequence set forth in SEQ ID N·:31, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID N·:32; or (b) a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence set forth in SEQ ID N·:49, an HCDR2 comprising the amino acid sequence set forth in SEQ ID N·:22, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID N·:23, and an LCDR1 comprising the amino acid sequence set forth in SEQ ID N·:50, an LCDR2 comprising the amino acid sequence set forth in SEQ ID N·:25, and a light chain variable region comprising an LCDR1 comprising the amino acid sequence set forth in SEQ ID N·:30, an LCDR2 comprising the amino acid sequence set forth in SEQ ID N·:31, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID N·:32. N·:26, wherein the first therapeutically effective dose of the antibody or antigen-binding fragment is 340 mg or 680 mg administered subcutaneously once a week, and optionally, the administration is for about 12 weeks or more.

[0019] In some embodiments, the method further comprises administering to the patient a second therapeutically effective amount of the antibody or antigen-binding fragment, wherein the second therapeutically effective amount is 340 mg administered subcutaneously once weekly, optionally for about 12 weeks or more.

[0020] In some embodiments, the method further comprises administering to the patient a third therapeutically effective amount of the antibody or antigen-binding fragment, wherein the patient has recurrent CIDP, and wherein the third therapeutically effective amount is 680 mg administered subcutaneously once a week, optionally for about 4 weeks or more; and optionally, 340 mg administered subcutaneously once a week for a period thereafter.

[0021] In some embodiments, the patient is a human. [Brief explanation of the drawings]

[0022] [Figure 1] Figure 1 is a schematic diagram illustrating a phase 2B trial of an anti-FcRn antibody for the treatment of CIDP. Four cohorts (A–D) were defined based on CIDP treatment at screening. Participants in cohorts A, B, and D who had not progressed by week 0 were withdrawn from the study at week 0. Non-responders in phase 1 who completed phase 1 were withdrawn from the study after completing week 12 and the subsequent 4-week follow-up visit (F·ll·w-Up visit). Non-responders in phase 1 who required protocol-prohibited rescue therapy before week 12 could discontinue IMP administration and return to standard of care. These participants were encouraged to remain in the study for safety follow-up observations (Safety F·ll·w-Up) until week 12 and through the follow-up visit. Participants who completed phase 2 without relapse or recurrence were eligible to participate in the long-term extension study (L·ng-Term Extension study).

[0023] Abbreviations: CIDP = chronic inflammatory demyelinating polyneuropathy; EAN / PNS = European Academy of Neurology / Peripheral Nerve Society; Ig = immunoglobulin (IVIg and SCIg) therapy; IMP = investigational drug; LTE = long-term extension; PLEX = plasma exchange; QW = weekly; Wk = weekly; SC = subcutaneous; INCAT = Inflammat·ry Neur·pathy Cause and Treatment DETAILED DESCRIPTION OF THE INVENTION

[0024] Certain terms are defined throughout the detailed description so that the present disclosure can be more easily understood. Unless otherwise defined herein, all scientific and technical terms used in connection with the present disclosure have the same meaning as commonly understood by those skilled in the art. All references cited herein are incorporated by reference for all purposes. If the cited references contradict the disclosure of this specification, the present specification shall prevail.

[0025] As used herein, the singular forms of words include the plural forms unless the context clearly dictates otherwise. For example, the terms "a," "an," and "the" are understood as either singular or plural. For example, "an element" means one or more elements. The term "or" means "and / or" unless expressly stated otherwise. All ranges expressed as "between value X and value Y" are intended to be inclusive of the endpoints and encompass all values ​​therebetween, unless the context dictates otherwise.

[0026] In some embodiments, the present disclosure relates to methods for treating CIDP by administering an anti-FcRn antibody or antigen-binding fragment thereof, or a pharmaceutical composition comprising at least one pharmaceutically acceptable carrier and an anti-FcRn antibody or antigen-binding fragment thereof. In some embodiments, the present disclosure relates to the use of an anti-FcRn antibody or antigen-binding fragment thereof in methods for treating CIDP by administering an anti-FcRn antibody or antigen-binding fragment thereof, or a pharmaceutical composition comprising at least one pharmaceutically acceptable carrier and an anti-FcRn antibody or antigen-binding fragment thereof. In some embodiments, the present disclosure relates to the use of an anti-FcRn antibody or antigen-binding fragment thereof in the manufacture of a medicament for the treatment of CIDP. In some embodiments, the present disclosure relates to an anti-FcRn antibody or antigen-binding fragment thereof for use in methods for treating CIDP. Pharmaceutical compositions comprising an anti-FcRn antibody or antigen-binding fragment thereof and at least one pharmaceutically acceptable carrier are also disclosed and are useful for the treatment methods and uses described herein.

[0027] As used herein, the term "treating" and its cognates refer to the amelioration of a disease, disorder, or condition (e.g., CIDP) or at least one discernible symptom thereof (e.g., one or more of the signs and symptoms described herein). The term "treating" includes, but is not limited to, a complete cure or complete amelioration of one or more symptoms of CIDP. In some embodiments, "treating" refers to at least a partial improvement of at least one measurable physical parameter, which may not be discernible to the patient. For example, a reduction in at least one autoantibody and / or pathogenic antibody (e.g., pathogenic IgG) and / or total serum IgG levels. In some embodiments, "treating" refers to inhibiting the progression of CIDP, which may be physical (e.g., stabilization of discernible symptoms), physiological (e.g., stabilization of physical parameters), or both. In some embodiments, "treating" refers to slowing or reversing the progression of CIDP.

[0028] The antibodies, antigen-binding fragments, and pharmaceutical compositions disclosed herein can also be used for the prevention or prophylactic treatment of CIDP. For example, a method of prevention can include administering an antibody, antigen-binding fragment, or pharmaceutical composition disclosed herein to a subject at risk of developing CIDP, thereby preventing or reducing the likelihood of developing CIDP or at least one discernible symptom thereof.

[0029] As used herein, the terms "subject" and "patient" are used interchangeably herein and refer to a human or a non-human animal. Non-human animals include all vertebrates (e.g., mammals and non-mammals), and non-limiting examples of mammals include humans, mice, rats, rabbits, dogs, monkeys, and pigs. In various embodiments, the subject is a human. In various embodiments, the subject is a human who has or is suspected of having CIDP.

[0030] In some embodiments, patients in need of treatment for CIDP include those who exhibit one or more signs and symptoms of CIDP (e.g., symmetric muscle weakness in both proximal and distal muscles of the hips, shoulders, hands, and / or feet, impaired motor function, altered or lost sensation, loss of coordination, hypoesthesia, tingling or pins and needles, fatigue, burning sensation, pain, clumsiness, difficulty swallowing, double vision, muscle atrophy, diminished or absent deep tendon reflexes, abnormal gait, and / or impaired response to various sensory stimuli, etc.) or have been otherwise diagnosed with the disease by a physician.

[0031] In some embodiments, a patient (or a sample obtained from a patient) in need of treatment for CIDP has a detectable level of anti-myelinating peripheral nerve IgG. In some embodiments, the anti-myelinating peripheral nerve IgG is present in the patient's blood. In some embodiments, the anti-myelinating peripheral nerve IgG is anti-myelinating peripheral nerve IgG1. In some embodiments, the anti-myelinating peripheral nerve IgG is anti-myelinating peripheral nerve IgG2. In some embodiments, the anti-myelinating peripheral nerve IgG is anti-myelinating peripheral nerve IgG3. In some embodiments, the anti-myelinating peripheral nerve IgG is anti-myelinating peripheral nerve IgG4.

[0032] In some embodiments, a patient in need of treatment (or a sample obtained from a patient) has detectable levels of anti-paranode IgG. In some embodiments, the anti-paranode IgG is present in the patient's blood. In some embodiments, the anti-paranode IgG is anti-paranode IgG1. In some embodiments, the anti-paranode IgG is anti-paranode IgG2. In some embodiments, the anti-paranode IgG is anti-paranode IgG3. In some embodiments, the anti-paranode IgG is anti-paranode IgG4. Paranode antigen proteins include, for example, NF-155 and contactin-1.

[0033] One embodiment is a method for treating CIDP, comprising administering to a patient in need of such treatment (i) a therapeutically effective amount of an anti-FcRn antibody or its antigen-binding fragment, or (ii) a pharmaceutical composition comprising at least one pharmaceutically acceptable carrier and a therapeutically effective amount of an anti-FcRn antibody or its antigen-binding fragment.

[0034] Another embodiment is an anti-FcRn antibody or antigen-binding fragment thereof for use in a method for treating CIDP in a patient in need thereof, the method comprising administering to the patient (i) a therapeutically effective amount of the antibody or antigen-binding fragment, or (ii) a pharmaceutical composition comprising at least one pharmaceutically acceptable carrier and a therapeutically effective amount of the antibody or antigen-binding fragment.

[0035] Another embodiment is the use of an anti-FcRn antibody or antigen-binding fragment thereof in a method for treating CIDP in a patient in need thereof, comprising administering to the patient (i) a therapeutically effective amount of the antibody or antigen-binding fragment, or (ii) a pharmaceutical composition comprising at least one pharmaceutically acceptable carrier and a therapeutically effective amount of the antibody or antigen-binding fragment.

[0036] Another embodiment relates to the use of an anti-FcRn antibody or antigen-binding fragment thereof in the manufacture of a medicament for treating CIDP in a patient in need thereof.

[0037] In various embodiments of the therapeutic methods, uses, and compositions disclosed herein, the anti-FcRn antibody or antigen-binding fragment acts as a non-competitive inhibitor of IgG binding to FcRn. In various embodiments, binding of the antibody or antigen-binding fragment to FcRn inhibits binding of at least one autoantibody and / or pathogenic antibody to FcRn. In various embodiments, this inhibition promotes clearance of at least one autoantibody and / or pathogenic antibody from the subject's body. In various embodiments, such inhibition reduces the half-life of at least one autoantibody and / or pathogenic antibody. In various embodiments, such inhibition reduces the level of at least one autoantibody and / or pathogenic antibody in the subject and / or a sample from the subject. In various embodiments, a reduction in the level of at least one autoantibody and / or pathogenic antibody results in or correlates with an improvement in at least one clinical parameter of CIDP.

[0038] As used herein, the term "autoantibody" refers to an antibody produced by a body's immune system that targets one or more of the body's own proteins, tissues, and / or organs. For example, one or more autoantibodies may be produced when a human patient's immune system is unable to distinguish between "self" and "non-self." In some embodiments, the autoantibody is a pathogenic antibody (e.g., a pathogenic IgG, e.g., pathogenic IgG1, IgG2, IgG3, or IgG4). As used herein, the term "pathogenic antibody" refers to an antibody (e.g., an autoantibody) that is involved in or causes the pathogenesis of one or more diseases, disorders, or conditions (e.g., CIDP).

[0039] In some embodiments, the pathogenic antibody is a pathogenic IgG (e.g., pathogenic IgG1, IgG2, IgG3, or IgG4). In some embodiments, the pathogenic antibody and / or pathogenic IgG is an anti-myelinating peripheral nerve IgG antibody. In some embodiments, the pathogenic antibody is an anti-paranodal IgG.

[0040] In some embodiments, treating a patient with an antibody, antigen-binding fragment, or pharmaceutical composition described herein, e.g., by using the methods described herein, reduces levels of anti-myelinating peripheral nerve IgG antibodies (e.g., anti-myelinating peripheral nerve IgG1, anti-myelinating peripheral nerve IgG2, anti-myelinating peripheral nerve IgG3, and / or anti-myelinating peripheral nerve IgG4) by at least about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 95% compared to anti-myelinating peripheral nerve IgG levels before treatment. In some embodiments, treatment of a patient with an antibody, antigen-binding fragment, or pharmaceutical composition described herein, e.g., using the methods described herein, reduces the level of anti-paranode IgG (e.g., anti-paranode IgG1, anti-paranode IgG2, anti-paranode IgG3, and / or anti-paranode IgG4) by at least about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 95%, i.e., reduced compared to the level of anti-paranode IgG before treatment.

[0041] In some embodiments, the autoantibody and / or pathogenic antibody is IgG, IgM, IgA, IgD, or IgE. In some embodiments, the autoantibody and / or pathogenic antibody is IgG (e.g., pathogenic IgG). In some embodiments, the autoantibody and / or pathogenic antibody is IgG1, IgG2, IgG3, or IgG4. In some embodiments, the autoantibody and / or pathogenic antibody is IgG1 (e.g., pathogenic IgG1, e.g., anti-paranodal IgG1 or anti-myelinating neuron IgG1). In some embodiments, the autoantibody and / or pathogenic antibody is IgG2 (e.g., pathogenic IgG2, e.g., anti-paranodal IgG2 or anti-myelinating neuron IgG2). In some embodiments, the autoantibody and / or pathogenic antibody is IgG3 (e.g., pathogenic IgG3, e.g., anti-paranodal IgG3 or anti-myelinating neuron IgG3). In some embodiments, the autoantibody and / or pathogenic antibody is an IgG4 (e.g., a pathogenic IgG4, e.g., an anti-paranodal IgG4 or an anti-myelinating neuron IgG4). In some embodiments, the autoantibody is a pathogenic antibody.

[0042] In various embodiments of the therapeutic methods, uses, and compositions disclosed herein, the anti-FcRn antibody or antigen-binding fragment can non-competitively inhibit the binding of at least one autoantibody and / or pathogenic antibody (e.g., at least one IgG) to FcRn at physiological pH (i.e., pH 7.0-7.4). Without being bound by theory, it is believed that FcRn binds to its ligand (i.e., IgG) and exhibits no substantial affinity for IgG at physiological pH but not at acidic pH. Thus, in various embodiments, at physiological pH, the anti-FcRn antibody or antigen-binding fragment can act as a non-competitive inhibitor of IgG binding to FcRn, and the binding of the anti-FcRn antibody or antigen-binding fragment to FcRn is not affected by the presence of IgG. Thus, in various embodiments, an anti-FcRn antibody or antigen-binding fragment that specifically binds to FcRn and is non-competitive with IgG in a pH-independent manner has the advantage of being able to provide therapeutic or prophylactic effects at significantly lower concentrations through IgG FcRn-mediated signaling, compared to conventional competitive inhibitors (i.e., antibodies) that bind to FcRn competitively with IgG. Furthermore, in various embodiments, while transporting intracellularly while bound to FcRn, the anti-FcRn antibody or antigen-binding fragment can maintain its binding to FcRn with higher affinity than IgG in the blood. Thus, in various embodiments, the anti-FcRn antibody or antigen-binding fragment inhibits IgG from binding to FcRn, even in endosomes, which are acidic pH environments where IgG can bind to FcRn, thereby promoting IgG clearance. In various embodiments, the anti-FcRn antibody or antigen-binding fragment is RVT-1401 (also referred to herein as HL161BKN and bat·climab). In some embodiments, the antibody or antigen-binding fragment is RVT-1401, or an antigen-binding fragment thereof. RVT-1401 / batoclimab is described, for example, in International Patent Application Publication WO2015 / 167293 (referred to herein as HL161BKN), the entire contents of which are incorporated herein by reference.

[0043] Exemplary CDR sequences of anti-FcRn antibodies are shown in Table 1.

[0044] [Table 1]

[0045] In some embodiments, the antibody or antigen-binding fragment comprises three heavy chain CDR amino acid sequences: SEQ ID N·:27 (HCDR1), SEQ ID N·:28 (HCDR2), and SEQ ID N·:29 (HCDR3), and three light chain CDR amino acid sequences: SEQ ID N·:30 (LCDR1), SEQ ID N·:31 (LCDR2), and SEQ ID N·:32 (LCDR3). In some embodiments, the antibody or antigen-binding fragment comprises three heavy chain CDR amino acid sequences: SEQ ID N·:49 (HCDR1), SEQ ID N·:22 (HCDR2), and SEQ ID N·:23 (HCDR3), and three light chain CDR amino acid sequences: SEQ ID N·:50 (LCDR1), SEQ ID N·:25 (LCDR2), and SEQ ID N·:26 (LCDR3).

[0046] Exemplary heavy and light chain variable regions of anti-FcRn antibodies are shown in Table 2.

[0047] [Table 2]

[0048] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain variable region comprising an amino acid sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N·:6, and a light chain variable region comprising an amino acid sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N·:16. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain amino acid sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N·:46, and a light chain amino acid sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N·:48. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain amino acid sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N·:51, and a light chain amino acid sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N·:52.

[0049] In some embodiments, the antibody or antigen-binding fragment comprises the heavy chain variable region amino acid sequence of SEQ ID N·:6 and the light chain variable region amino acid sequence of SEQ ID N·:16. In some embodiments, the antibody or antigen-binding fragment comprises the heavy chain amino acid sequence of SEQ ID N·:46 and the light chain amino acid sequence of SEQ ID N·:48. In some embodiments, the antibody or antigen-binding fragment comprises the heavy chain amino acid sequence of SEQ ID N·:51 and the light chain amino acid sequence of SEQ ID N·:52.

[0050] Exemplary heavy and light chains of anti-FcRn antibodies are shown in Table 3.

[0051] [Table 3-1]

[0052] [Table 3-2]

[0053] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising an amino acid sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N·:46, 53, or 55, and a light chain comprising an amino acid sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N·:48, 54, or 56. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising the sequence set forth in SEQ ID N·:46, 53, or 55, and a light chain comprising the sequence set forth in SEQ ID N·:48, 54, or 56.

[0054] Binding "affinity" refers to the strength of the interaction between an antibody and an antigen at a single antigenic site. Within each antigenic site, the variable regions of the antibody "arms" interact with the antigen at multiple sites through weak non-covalent forces. Generally, the more interactions, the higher the affinity.

[0055] As used herein, the terms "specific," "specifically binds," and "specifically binds" refer to the binding reaction between an antibody or its antigen-binding fragment (e.g., an anti-FcRn antibody or its antigen-binding fragment) and a target antigen (e.g., FcRn) in a heterogeneous population of proteins and other biological substances. An antibody can be tested for binding specificity by comparing binding to the appropriate antigen with binding to alternative antigens or a mixture of antigens under defined conditions. An antibody is considered specific if it binds to the appropriate antigen with at least two-fold, at least five-fold, or at least ten-fold (or more) higher affinity than the alternative antigens or mixture of antigens.

[0056] A "specific antibody" or "target-specific antibody" is an antibody that binds only to a target antigen (e.g., FcRn) and does not bind (or shows minimal binding) to other antigens. In some embodiments, an antibody or antigen-binding fragment thereof that specifically binds to a target antigen (e.g., FcRn) has a specific binding activity of 1×10 at pH 6.0 or pH 7.4. -6 Less than M, 1 x 10 -7 Less than M, 1 x 10 -8 Less than M, 1 x 10 -9 Less than M, 1 x 10 -10 Less than M, 1 x 10 -11 Less than M, 1 x 10 -12 Less than M or 1 x 10 -13 In some embodiments, the KD is about 0.01 nM to about 2 nM at pH 6.0 or pH 7.4. In some embodiments, the KD is about 300 pM or less to about 2 nM or less at pH 7.4. In some embodiments, the KD is about 2 nM or less to about 900 pM or less at pH 6.0.

[0057] As used herein, the term "KD" refers to the equilibrium dissociation constant of antibody-antigen binding, which is obtained from the ratio of kd to ka (i.e., kd / ka) and is generally expressed as a molar concentration (M). The terms "kass·c" or "ka" refer to the on-rate of a particular antibody-antigen interaction, and the terms "kdis" or "kd" refer to the off-rate of a particular antibody-antigen interaction. Measurements of kd and / or ka can be performed at 25°C or 37°C. KD values ​​for antibodies and antigen-binding fragments can be determined using methods well-established in the art (see, e.g., P·llard, M·l. Bi·l. Cell 21(23):4061-7, 2010). In some embodiments, KD is measured by direct binding and / or competitive binding assays (e.g., surface plasmon resonance and / or competitive ELISA). In some embodiments, KD is measured by surface plasmon resonance (e.g., human FcRn-immobilized surface plasmon resonance). In some embodiments, the KD of the anti-FcRn antibodies or antigen-binding fragments disclosed herein is measured by human FcRn-immobilized surface plasmon resonance.

[0058] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, the anti-FcRn antibody or antigen-binding fragment has a KD (dissociation constant) of about 0.01 nM to about 2 nM at pH 6.0 and pH 7.4, as determined, for example, by surface plasmon resonance. In some embodiments, the anti-FcRn antibody or antigen-binding fragment has a KD of about 300 nM or less to about 2 nM or less at pH 7.4 and / or a KD of about 2 nM or less to about 900 pM or less at pH 6.0, as determined, for example, by surface plasmon resonance. In some embodiments, the anti-FcRn antibody or antigen-binding fragment binds to the outside of the cell and remains bound to endosomes in the bound state. In some embodiments, the anti-FcRn antibody or antigen-binding fragment effectively blocks the binding of one or more autoantibodies to FcRn (e.g., human FcRn), as determined, for example, by blocking analysis using human FcRn-expressing cells and FACS.

[0059] As used herein, the terms "anti-FcRn antibody" or "antibody that specifically binds to FcRn" refer to any form of antibody or antigen-binding fragment thereof that specifically binds to FcRn, including, for example, those that bind with a KD of less than 2 nM at pH 6.0 or pH 7.4 as determined by surface plasmon resonance (e.g., human FcRn-immobilized surface plasmon resonance). This term includes monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, and biologically functional fragments that specifically bind to FcRn.

[0060] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, the anti-FcRn antibody or antigen-binding fragment comprises: - a CDR1 comprising an amino acid sequence that is at least 90% identical to one or more amino acid sequences selected from the group consisting of SEQ ID N: 21, 24, 27, 30, 33, 36, 39, 42, 49, and 50; - a CDR2 comprising an amino acid sequence that is at least 90% identical to one or more amino acid sequences selected from the group consisting of SEQ ID N: 22, 25, 28, 31, 34, 37, 40, and 43; and - a CDR3 comprising an amino acid sequence that is at least 90% identical to one or more amino acid sequences selected from the group consisting of SEQ ID N·: 23, 26, 29, 32, 35, 38, 41, and 44.

[0061] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, the anti-FcRn antibody or antigen-binding fragment comprises: - a CDR1 comprising an amino acid sequence that is at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to one or more amino acid sequences selected from the group consisting of SEQ ID N·: 21, 24, 27, 30, 33, 36, 39, 42, 49, and 50; - a CDR2 comprising an amino acid sequence at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to one or more amino acid sequences selected from the group consisting of SEQ ID N·: 22, 25, 28, 31, 34, 37, 40, and 43; and - a CDR3 comprising an amino acid sequence that is at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to one or more amino acid sequences selected from the group consisting of SEQ ID N·:23, 26, 29, 32, 35, 38, 41, and 44.

[0062] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, the anti-FcRn antibody or antigen-binding fragment may comprise one or more amino acid deletions, additions, or substitutions in the amino acid sequences described herein.

[0063] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, the anti-FcRn antibody or antigen-binding fragment may comprise an amino acid sequence identical or homologous to an amino acid sequence described herein. The term "identity" or "homology" (h·m·l·gy) refers to the relationship between two or more polypeptide sequences, as determined by comparing the sequences. The term "identity" also refers to the degree of sequence relatedness between polypeptides, as determined by the number of matches between two or more strings of amino acid residues. The "percent identity" between two sequences is a function of the number of identical positions shared by the sequences (i.e., percent identity = number of identical positions / total number of positions × 100), taking into account the number of intervals and the length of each interval that must be introduced to optimally align the two sequences. Sequence comparison and percent identity determination between two sequences can be performed using a mathematical algorithm. For sequence comparison, typically, one sequence serves as a reference sequence, to which a test sequence is compared. When using a sequence comparison algorithm, the test and reference sequences are input into a computer, subsequence coordinates are designated as necessary, and sequence algorithm program parameters are designated. Default program parameters can be used, or alternative parameters can be designated. The sequence comparison algorithm then calculates the percent sequence identity of the test sequence relative to the reference sequence based on the program parameters. Additionally or alternatively, the amino acid sequences disclosed herein can be used as a "query sequence" to perform a search against, for example, a public database to identify related sequences. For example, such a search can be performed using the BLAST program of Altschul et al. (J. M·l. Bi·l. 215:403-10, 1990).

[0064] Two sequences are "substantially identical" if a specified percentage of amino acid residues are the same (i.e., 60% identity, optionally 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% identity, or if not specified, over the entire sequence) when the two sequences are compared and aligned for maximum correspondence over a comparison window, or designated region, as determined using any of the following sequence comparison algorithms or by manual alignment and visual inspection. Optionally, the identity exists over a region at least about 10 amino acids in length, or over a region about 20, 50, 200, or more amino acids in length. In some embodiments, the anti-FcRn antibodies and antigen-binding fragments described herein comprise at least one amino acid sequence at least 90% identical to a sequence selected from the group consisting of SEQ ID N: 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20-48. In some embodiments, the anti-FcRn antibodies and antigen-binding fragments described herein comprise at least one amino acid sequence that is at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to a sequence selected from the group consisting of SEQ ID N·:2, 4, 6, 8, 10, 12, 14, 16, 18, and 20-48.

[0065] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain variable region comprising: - CDR1 comprising the amino acid sequence of SEQ ID N·:21, CDR2 comprising the amino acid sequence of SEQ ID N·:22, and CDR3 comprising the amino acid sequence of SEQ ID N·:23, - CDR1 comprising the amino acid sequence of SEQ ID N·:27, CDR2 comprising the amino acid sequence of SEQ ID N·:28, and CDR3 comprising the amino acid sequence of SEQ ID N·:29, - CDR1 comprising the amino acid sequence of SEQ ID N·:33, CDR2 comprising the amino acid sequence of SEQ ID N·:34, and CDR3 comprising the amino acid sequence of SEQ ID N·:35, - a CDR1 comprising the amino acid sequence of SEQ ID N·:39, a CDR2 comprising the amino acid sequence of SEQ ID N·:40, and a CDR3 comprising the amino acid sequence of SEQ ID N·:41, or - CDR1 comprising the amino acid sequence of SEQ ID N·:49, CDR2 comprising the amino acid sequence of SEQ ID N·:22, and CDR3 comprising the amino acid sequence of SEQ ID N·:23.

[0066] In some embodiments, the antibody or antigen-binding fragment comprises a light chain variable region comprising: - CDR1 comprising the amino acid sequence of SEQ ID N·:24, CDR2 comprising the amino acid sequence of SEQ ID N·:25, and CDR3 comprising the amino acid sequence of SEQ ID N·:26, - CDR1 comprising the amino acid sequence of SEQ ID N·:30, CDR2 comprising the amino acid sequence of SEQ ID N·:31, and CDR3 comprising the amino acid sequence of SEQ ID N·:32, - CDR1 comprising the amino acid sequence of SEQ ID N·:36, CDR2 comprising the amino acid sequence of SEQ ID N·:37, and CDR3 comprising the amino acid sequence of SEQ ID N·:38, - a CDR1 comprising the amino acid sequence of SEQ ID N·:42, a CDR2 comprising the amino acid sequence of SEQ ID N·:43, and a CDR3 comprising the amino acid sequence of SEQ ID N·:44, or - CDR1 comprising the amino acid sequence of SEQ ID N·:50, CDR2 comprising the amino acid sequence of SEQ ID N·:25, and CDR3 comprising the amino acid sequence of SEQ ID N·:26.

[0067] In some embodiments, the antibody or antigen-binding fragment comprises one or more heavy chain variable regions and one or more light chain variable regions selected from the group consisting of: - a heavy chain variable region comprising a CDR1 comprising the amino acid sequence of SEQ ID N·:21 (HCDR1), a CDR2 comprising the amino acid sequence of SEQ ID N·:22 (HCDR2), and a CDR3 comprising the amino acid sequence of SEQ ID N·:23 (HCDR3), and a light chain variable region comprising a CDR1 comprising the amino acid sequence of SEQ ID N·:24 (LCDR1), a CDR2 comprising the amino acid sequence of SEQ ID N·:25 (LCDR2), and a CDR3 comprising the amino acid sequence of SEQ ID N·:26 (LCDR3); - a heavy chain variable region comprising a CDR1 comprising the amino acid sequence of SEQ ID N·:27 (HCDR1), a CDR2 comprising the amino acid sequence of SEQ ID N·:28 (HCDR2), and a CDR3 comprising the amino acid sequence of SEQ ID N·:29 (HCDR3), and a light chain variable region comprising a CDR1 comprising the amino acid sequence of SEQ ID N·:30 (LCDR1), a CDR2 comprising the amino acid sequence of SEQ ID N·:31 (LCDR2), and a CDR3 comprising the amino acid sequence of SEQ ID N·:32 (LCDR3); - a heavy chain variable region comprising a CDR1 comprising the amino acid sequence of SEQ ID N·:33 (HCDR1), a CDR2 comprising the amino acid sequence of SEQ ID N·:34 (HCDR2), and a CDR3 comprising the amino acid sequence of SEQ ID N·:35 (HCDR3), and a light chain variable region comprising a CDR1 comprising the amino acid sequence of SEQ ID N·:36 (LCDR1), a CDR2 comprising the amino acid sequence of SEQ ID N·:37 (LCDR2), and a CDR3 comprising the amino acid sequence of SEQ ID N·:38 (LCDR3); - a heavy chain variable region comprising a CDR1 comprising the amino acid sequence of SEQ ID N·:39 (HCDR1), a CDR2 comprising the amino acid sequence of SEQ ID N·:40 (HCDR2), and a CDR3 comprising the amino acid sequence of SEQ ID N·:41 (HCDR3), and a light chain variable region comprising a CDR1 comprising the amino acid sequence of SEQ ID N·:42 (LCDR1), a CDR2 comprising the amino acid sequence of SEQ ID N·:43 (LCDR2), and a CDR3 comprising the amino acid sequence of SEQ ID N·:44 (LCDR3), and - a heavy chain variable region comprising a CDR1 having the amino acid sequence of SEQ ID N·:49 (HCDR1), a CDR2 having the amino acid sequence of SEQ ID N·:22 (HCDR2), and a CDR3 having the amino acid sequence of SEQ ID N·:23 (HCDR3), and a light chain variable region comprising a CDR1 having the amino acid sequence of SEQ ID N·:50 (LCDR1), a CDR2 having the amino acid sequence of SEQ ID N·:25 (LCDR2), and a CDR3 having the amino acid sequence of SEQ ID N·:26 (LCDR3).

[0068] In some embodiments, the antibody or antigen-binding fragment comprises one or more heavy chain variable regions and / or one or more light chain variable regions comprising one or more amino acid sequences selected from the group consisting of the amino acid sequences of SEQ ID N·:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 51, and 52.

[0069] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID N·:2, 4, 6, 8, 10, or 51, and / or a light chain variable region comprising the amino acid sequence of SEQ ID N·:12, 14, 16, 18, 20, or 52.

[0070] In some embodiments, the antibody or antigen-binding fragment comprises one or more heavy chain variable regions and one or more light chain variable regions selected from the group consisting of: - a heavy chain variable region comprising the amino acid sequence of SEQ ID N·:2 and a light chain variable region comprising the amino acid sequence of SEQ ID N·:12; - a heavy chain variable region comprising the amino acid sequence of SEQ ID N·:4 and a light chain variable region comprising the amino acid sequence of SEQ ID N·:14; - a heavy chain variable region comprising the amino acid sequence of SEQ ID N·:6 and a light chain variable region comprising the amino acid sequence of SEQ ID N·:16; - a heavy chain variable region comprising the amino acid sequence of SEQ ID N·:8 and a light chain variable region comprising the amino acid sequence of SEQ ID N·:18; - a heavy chain variable region comprising the amino acid sequence of SEQ ID N·:10 and a light chain variable region comprising the amino acid sequence of SEQ ID N·:20, and - a heavy chain variable region comprising the amino acid sequence of SEQ ID N·:51 and a light chain variable region comprising the amino acid sequence of SEQ ID N·:52.

[0071] As used herein with respect to antibodies, the terms "fragment," "antibody fragment," and "antigen-binding fragment" all refer to one or more fragments of a full-length antibody that retain the ability to specifically bind to a target antigen (e.g., FcRn) and / or provide a function of the full-length antibody (e.g., non-competitive interference with IgG binding to FcRn). Antigen-binding fragments can also be present in larger macromolecules, such as bispecific, trispecific, and multispecific antibodies, e.g., diabodies, triabodies, and tetrabodies. Examples of antigen-binding fragments include, but are not limited to, single-chain antibodies, Fab fragments, F(ab')2 fragments, Fds, scFvs, domain antibodies, bispecific antibodies, minibodies, scaps (sterol regulatory binding protein cleavage activating proteins), chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, and small modular immunopharmaceuticals (SMIPs).

[0072] In some embodiments, the antibody or antigen-binding fragment is a binding domain immunoglobulin fusion protein, a camelized antibody, a VHH-containing antibody, an IgD antibody, an IgE antibody, an IgM antibody, an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody. In some embodiments, the antibody or antigen-binding fragment comprises a derivative of an antibody constant region. In some embodiments, the antibody or antigen-binding fragment is a synthetic antibody based on a protein scaffold capable of binding to FcRn.

[0073] In some embodiments, antigen-binding fragments exhibit the same or similar properties as full-length antibodies. Without limitation, antigen-binding fragments can be prepared by any suitable method known in the art. For example, the various antigen-binding fragments described herein can be prepared by enzymatic or chemical modification of full-length antibodies, synthesized de novo using recombinant DNA methodologies (e.g., scFv), or identified using phage display libraries (see, e.g., Pini and Bracci, Curr. Pr·tein Pept. Sci. 1(2):155-69, 2000). Antigen-binding fragments can be screened for utility (e.g., specificity, binding affinity, activity) in the same manner as full-length antibodies.

[0074] Furthermore, antibodies or antigen-binding fragments with mutations in the variable and / or constant regions can be used in the therapeutic methods, applications, and compositions described herein. Examples of such antibodies or antigen-binding fragments include antibodies with conservative substitutions of amino acid residues in the variable and / or constant regions. As used herein, the term "conservative substitution" refers to the substitution of an amino acid residue with another amino acid residue with similar properties to the original amino acid residue. For example, lysine, arginine, and histidine have similar properties in that they have basic side chains, while aspartic acid and glutamic acid have similar properties in that they have acidic side chains. Furthermore, glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, and tryptophan have similar properties in that they have uncharged polar side chains, and alanine, valine, leucine, threonine, isoleucine, proline, phenylalanine, and methionine have similar properties in that they have nonpolar side chains. Therefore, as will be apparent to those skilled in the art, substitution of amino acid residues within a group exhibiting similar properties is unlikely to result in a substantial change in the properties of the antibody or antigen-binding fragment.

[0075] In some embodiments, the antibodies or antigen-binding fragments can be conjugated to other substances (e.g., therapeutic agents or detectable labels). Substances that can be conjugated to or co-administered with the antibodies or antigen-binding fragments described herein include, but are not limited to, therapeutic agents commonly used to treat CIDP (e.g., standard therapeutic agents, e.g., one or more of the standard therapeutic agents described or incorporated by reference herein), agents capable of inhibiting the activity of FcRn, and moieties that can be physically associated with the antibodies or antigen-binding fragments, e.g., moieties to improve stabilization and / or retention time in blood, serum, lymph, or other tissues. For example, the antibodies or antigen-binding fragments can be associated with polymers, e.g., non-antigenic polymers such as polyalkylene oxides or polyethylene oxides. Suitable polymers vary considerably by weight. Polymers with number-average molecular weights ranging from about 200 to about 35,000 (or from about 1,000 to about 15,000 and from 2,000 to about 12,500) can be used. For example, the antibody or antigen-binding fragment can be conjugated to a water-soluble polymer, e.g., a hydrophilic polyvinyl polymer such as polyvinyl alcohol and polyvinylpyrrolidone. Non-limiting examples of such polymers include polyalkylene oxide homopolymers such as polyethylene glycol (PEG) or polypropylene glycol, polyoxyethylated polyols, and copolymers and block copolymers thereof, provided that the water solubility of the block copolymer is maintained.

[0076] In various embodiments, the antibody or antigen-binding fragment binds to FcRn with a KD (dissociation constant) of 0.01 nM to 2 nM at pH 6.0 or pH 7.4, as measured, for example, by surface plasmon resonance.

[0077] RVT-1401 (also referred to herein as HL161BKN) is an example of an anti-FcRn antibody. In some embodiments, the antibody or antigen-binding fragment is RVT-1401, or an antigen-binding fragment thereof. In some embodiments, the antibody or antigen-binding fragment comprises the three heavy chain CDR amino acid sequences of RVT-1401 (HCDR1 (SEQ ID N·:27), HCDR2 (SEQ ID N·:28), HCDR3 (SEQ ID N·:29)) and the three light chain CDR amino acid sequences of RVT-1401 (LCDR1 (SEQ ID N·:30), LCDR2 (SEQ ID N·:31), LCDR3 (SEQ ID N·:32)). In some embodiments, the antibody or antigen-binding fragment comprises the heavy chain variable region amino acid sequence of RVT-1401 (SEQ ID N·:6) and the light chain variable region amino acid sequence of RVT-1401 (SEQ ID N·:16). In some embodiments, the antibody or antigen-binding fragment comprises the heavy chain amino acid sequence of RVT-1401 (SEQ ID N·:46) and the light chain amino acid sequence of RVT-1401 (SEQ ID N·:48).

[0078] In various embodiments of the therapeutic methods and uses disclosed herein, the antibody or antigen-binding fragment is administered alone. In various embodiments, the antibody or antigen-binding fragment is administered in combination with at least one additional therapeutic regimen. In various embodiments, the at least one additional therapeutic regimen may comprise or consist of a standard of care regimen or treatment for CIDP.

[0079] As used herein, "concomitant administration" or "co-administration" refers to the provision of two or more different therapies to a subject while the subject is suffering from CIDP. For example, in some embodiments, two or more therapies are delivered after the subject is diagnosed with the disease and before the disease is cured or eliminated, or after the subject is identified as being at risk but before the onset of disease symptoms. In some embodiments, overlap occurs when delivery of one treatment is ongoing and delivery of a second treatment is initiated. In some embodiments, the first and second treatments are initiated simultaneously. This type of delivery is sometimes referred to herein as "simultaneous," "concurrent," or "combined" delivery. In other embodiments, delivery of one treatment is completed and delivery of the second treatment is initiated. This type of delivery is sometimes referred to herein as "continuous" or "sequential" delivery. In some embodiments, the antibody or antigen-binding fragment and at least one additional therapeutic agent are administered simultaneously. In some embodiments, the antibody or antigen-binding fragment and at least one additional therapeutic agent are administered sequentially.

[0080] In some embodiments, the two therapies (e.g., an anti-FcRn antibody or antigen-binding fragment and a second therapeutic modality) are present in the same composition. Such a composition can be administered in an appropriate form and via an appropriate route. In other embodiments, the two therapies (e.g., an anti-FcRn antibody or antigen-binding fragment and a second therapeutic modality) are administered in separate compositions in an appropriate form and via an appropriate route. For example, a composition comprising an anti-FcRn antibody or antigen-binding fragment and a composition comprising a second therapeutic modality (e.g., a standard treatment for CIDP) can be administered in any order, concurrently or sequentially, at different times; in either case, they must be administered sufficiently close in time to provide the desired therapeutic or prophylactic effect.

[0081] As used herein, the term "therapeutic agent" refers to a chemical compound, a mixture of chemical compounds, a biological macromolecule, or an extract made from biological materials. The term "therapeutic agent" or "drug" refers to a therapeutic agent that can modulate a biological process or has biological activity. The anti-FcRn antibodies and antigen-binding fragments described herein are examples of therapeutic agents.

[0082] As used herein, the term "standard-·f-care agent" refers to any therapeutic agent or other form of therapy that is recognized as an appropriate treatment for a particular type of disease (e.g., febrile autoimmune hemolytic anemia). As used herein, the term "standard d·sage" or "standard d·sing regimen" refers to the usual or routine dosing regimen for a therapeutic agent, e.g., a regimen proposed by a manufacturer, approved by a regulatory agency, or tested in human subjects to meet the needs of the average patient.

[0083] Examples of standard therapies and treatments for CIDP include glucocorticoids (steroids), intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin (SCIg), and plasma exchange (PLEx).

[0084] The anti-FcRn antibodies and antigen-binding fragments described herein can be administered in combination with any of the exemplary standard of care treatments or regimens described herein. In some embodiments, the anti-FcRn antibodies and antigen-binding fragments described herein are administered in combination with glucocorticoids (steroids) or plasma exchange (PLEx). In some embodiments, the anti-FcRn antibodies and antigen-binding fragments described herein are administered in combination with intravenous immunoglobulin (IVIg) and / or subcutaneous immunoglobulin (SCIg). In some embodiments, the anti-FcRn antibodies and antigen-binding fragments described herein are not administered in combination with any of the exemplary standard of care treatments or therapies described herein. In some embodiments, the anti-FcRn antibodies and antigen-binding fragments described herein are administered alone or in combination with no other treatments or therapies.

[0085] Also provided herein is a pharmaceutical composition comprising an anti-FcRn antibody or its antigen-binding fragment formulated with at least one pharmaceutically acceptable carrier. The composition may include one or more additional therapeutic agents suitable for treating, for example, CIDP. Methods for formulating pharmaceutical compositions and suitable formulations are known in the art (see, for example, "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, PA). Suitable formulations vary depending on the route of administration.

[0086] As used herein, the term "pharmaceutical composition" refers to a formulation of an anti-FcRn antibody or antigen-binding fragment thereof and other ingredients suitable for administration to a patient, such as a pharmaceutically acceptable carrier and / or excipient. The pharmaceutical compositions provided herein may be suitable for in vitro and / or in vivo administration. In some embodiments, the pharmaceutical compositions provided herein are in a form that allows for administration and thereafter can provide the intended biological activity of the active ingredient and / or achieve a therapeutic effect. The pharmaceutical compositions provided herein preferably do not contain additional ingredients that have unacceptable toxicity to the subject to which the formulation is administered.

[0087] As used herein, the terms "pharmaceutically acceptable carrier" and "physiologically acceptable carrier" can be used interchangeably and refer to a carrier, diluent, or excipient that does not cause significant irritation to a subject and does not inhibit the biological activity and properties of an administered antibody or antigen-binding fragment. Thus, a pharmaceutically acceptable carrier is compatible with an active ingredient, such as an antibody or antigen-binding fragment thereof, and can include saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, or a mixture of two or more of these. A pharmaceutically acceptable carrier can be used to improve or stabilize a composition or to facilitate preparation of the composition. A pharmaceutically acceptable carrier can also include other known physiologically compatible additives, such as antioxidants, buffers, solvents, antibacterial agents, dispersion media, coating agents, antibacterial and antifungal agents, isotonic and absorption delaying agents, etc. The carrier can be selected to minimize adverse effects on the subject and / or to minimize degradation of the active ingredient. In some embodiments, the carrier comprises one or more of L-histidine hydrochloride, L-histidine, L-arginine hydrochloride, and / or polysorbate 20.

[0088] The term "excipient" as used herein refers to an inert substance added to a pharmaceutical composition to facilitate administration of an active ingredient. Formulations for parenteral administration may contain excipients such as, for example, sterile water or saline, polyalkylene glycols such as polyethylene glycol, vegetable oils, or hydrogenated naphthalenes. Other excipients include, but are not limited to, calcium bicarbonate, calcium phosphate, various sugars and starches, cellulose derivatives, gelatin, ethylene-vinyl acetate copolymer particles, and surfactants, including, for example, polysorbate 20.

[0089] In various embodiments of the therapeutic methods, uses, and compositions disclosed herein, the anti-FcRn antibody, antigen-binding fragment, or pharmaceutical composition can be administered by various methods known in the art. The route and / or method of administration varies depending on the desired results. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered orally, intravenously, intramuscularly, intra-arterially, intramedullary, intradurally, intracardially, transdermally, subcutaneously, intraperitoneally, intragastrointestinal, sublingually, or topically. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered orally or parenterally. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered parenterally, for example, intravenously or subcutaneously (e.g., by injection or infusion). In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered subcutaneously (e.g., by injection or infusion). In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered by one or more subcutaneous injections. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered in a single (i.e., single) subcutaneous injection. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered in two or more (e.g., two) consecutive subcutaneous injections. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered without intravenous administration (e.g., intravenous induction) prior to the one or more subcutaneous injections. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is delivered via a syringe, catheter, pump delivery system, or stent. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is delivered via a syringe (e.g., a pre-filled syringe). Depending on the route of administration, the active compound, i.e., the anti-FcRn antibody or antigen-binding fragment, can be coated with a material to protect it from the action of acids and other natural conditions that may inactivate the compound.

[0090] The antibody, antigen-binding fragment, or pharmaceutical composition can be formulated in various forms, such as powder, tablet, capsule, liquid, injectable, ointment, or syrup, and / or can be contained in a single-dose or multi-dose container, such as a sealed ampule, vial, or syringe. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated in an injectable form. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated as an aqueous solution, suspension, or emulsion with one or more excipients, diluents, dispersing agents, surfactants, binders, and / or lubricants. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is contained in a syringe (e.g., a pre-filled syringe). In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is contained in a syringe with and / or compatible with a small gauge needle (e.g., about 25 gauge or larger, about 26 gauge or larger, about 27 gauge or larger, about 28 gauge or larger, about 29 gauge or larger, and / or about 30 gauge or larger).

[0091] In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is formulated to achieve stability prior to administration and / or to prevent or minimize physical and / or chemical degradation. Physical instability can include processes such as denaturation and aggregation, and common chemical degradation pathways include, but are not limited to, cross-linking, deamidation, isomerization, oxidation, and fragmentation (see, e.g., Wang et al., J. Pharm. Sci. 91(1):1-26, 2007). As used herein, the term "stable" or "stability," when describing an antibody or antigen-binding fragment thereof, means that the antibody or antigen-binding fragment maintains activity (e.g., binding to FcRn) and / or maintains integrity such that it can achieve a therapeutic effect. In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is formulated with one or more pharmaceutically acceptable carriers (e.g., one or more excipients) to be stable under standard storage conditions. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated with one or more pharmaceutically acceptable carriers (e.g., one or more excipients) to be stable at high concentrations. In some embodiments, the antibody or antigen-binding fragment can be stably concentrated in the formulation to about 150 mg / mL or more. In some embodiments, the antibody or antigen-binding fragment can be stably concentrated in the formulation to about 170 mg / mL or more. In some embodiments, the antibody or antigen-binding fragment can be stably concentrated in the formulation to about 170 mg / mL or more (e.g., about 180 mg / mL, about 200 mg / mL, about 220 mg / mL, or more). In some embodiments, the stably concentrated formulation (e.g., a formulation comprising about 170 mg / mL or more of the antibody or antigen-binding fragment) has an acceptable viscosity suitable for administration through a small gauge needle. In some embodiments, the small gauge needle is about 25 gauge or larger, about 26 gauge or larger, about 27 gauge or larger, about 28 gauge or larger, about 29 gauge or larger, or about 30 gauge or larger.

[0092] The administration regimen of the anti-FcRn antibody or antigen-binding fragment, alone or in combination with one or more additional therapeutic agents or therapies, can be adjusted to provide the optimal desired response (e.g., therapeutic response). For example, a single bolus of the anti-FcRn antibody or antigen-binding fragment may be administered all at once, multiple divided doses may be administered over a predetermined period of time, or the dose of the anti-FcRn antibody or antigen-binding fragment may be proportionally reduced or increased depending on the needs of the therapeutic situation. For a particular subject, a specific administration regimen can be adjusted over time based on the individual needs and the professional judgment of the treating physician. For example, in some embodiments, the dose of the anti-FcRn antibody or antigen-binding fragment may be appropriately determined taking into account the patient's severity, condition, age, medical history, etc.

[0093] Anti-FcRn antibodies or antigen-binding fragments can be formulated into pharmaceutically acceptable dosage forms by methods known to those skilled in the art. For example, parenteral compositions can be formulated in dosage unit form for ease of administration and uniformity of dosage. As used herein, "dose unit form" refers to physically discrete units suitable for single administration to a subject, each unit containing a predetermined amount of active compound associated with a pharmaceutically acceptable carrier and calculated to produce a desired therapeutic effect. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated in dosage unit form. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated in dosage unit form for subcutaneous administration. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated in dosage unit form for administration as one or more subcutaneous injections (e.g., one subcutaneous injection, or two or more (e.g., two) consecutive subcutaneous injections). In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated in a dosage unit form (e.g., as one or more subcutaneous injections) for patient self-administration and / or administration by a medical practitioner.

[0094] The dosage of the anti-FcRn antibody or antigen-binding fragment, composition comprising the anti-FcRn antibody or antigen-binding fragment, and / or additional therapeutic agent may be selected depending on the unique characteristics of the active compound and the particular therapeutic effect to be achieved. A physician or veterinarian may begin administering the antibody or antigen-binding fragment at a level lower than that required to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. A physician or veterinarian may begin administering the antibody or antigen-binding fragment at a level higher than that required to achieve the desired therapeutic effect and gradually decrease the dosage until the desired effect is achieved. In general, the effective dose of an antibody or antigen-binding fragment for the treatment of CIDP will vary depending on many factors, including the stage of the disease, the severity of symptoms, and the subject's prognosis. The selected dosage level may vary depending on various pharmacokinetic factors, such as the particular composition or ester, salt, or amide thereof used, the route of administration, the time of administration, the excretion rate of the particular compound used, the duration of treatment, other drugs, compounds, and / or substances used in conjunction with the particular composition used, and the age, sex, weight, condition, general health, and previous medical history of the patient being treated. In some embodiments, treatment may be administered once or multiple times. Intermittent and / or chronic (continuous) administration strategies may be applied, taking into account the condition of a particular patient.

[0095] In some embodiments, a therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment is used in the methods, uses, and pharmaceutical compositions of the disclosure.

[0096] As used herein, the terms "therapeutically effective amount" and "therapeutically effective dose" are used interchangeably and refer to an amount sufficient to reduce at least one symptom or measurable parameter associated with a disease, disorder, or condition, an amount sufficient to normalize bodily function in a disease, disorder, or condition that results in impairment of a specific bodily function, and / or an amount sufficient to provide improvement in or slow the progression of one or more clinically measured parameters of a disease, disorder, or condition. A therapeutically effective amount may be, for example, an amount sufficient to treat, reduce the severity of, delay the onset of, and / or reduce the risk of onset of one or more symptoms of CIDP. The therapeutically effective amount and therapeutically effective administration frequency may be determined by methods known in the art and described herein. In some embodiments of the methods, uses, and compositions described herein, the anti-FcRn antibody or antigen-binding fragment is administered in a therapeutically effective amount when administered as a single formulation. In some embodiments, the anti-FcRn antibody or antigen-binding fragment and at least one additional therapeutic agent are each administered in a therapeutically effective amount when the formulations are used in combination. In some embodiments, a therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment is the amount necessary to reduce total serum IgG levels and / or the level of at least one autoantibody (e.g., at least one IgG) in a patient with or suspected of having CIDP.

[0097] In some embodiments, a therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment is the amount necessary to reduce the total serum IgG level and / or the level of at least one autoantibody and / or pathogenic antibody (e.g., at least one IgG) in a CIDP patient and / or a sample from a CIDP patient by at least about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, or about 80% compared to the level before treatment with the anti-FcRn antibody or antigen-binding fragment. In some embodiments, a therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment is the amount required to reduce the total serum IgG level and / or the level of at least one autoantibody and / or pathogenic antibody (e.g., at least one IgG) in a CIDP patient and / or a sample from a CIDP patient by at least about 40%, about 50%, about 60%, about 70%, or about 80% compared to the level before treatment with the anti-FcRn antibody or antigen-binding fragment. In some embodiments, a therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment is the amount required to reduce the serum endogenous IgG concentration in a CIDP patient and / or a sample from a CIDP patient to less than about 40%, about 50%, about 60%, about 70%, or about 80% of the pre-treatment level. In some embodiments, the autoantibody is anti-myelin peripheral nerve IgG. In some embodiments, the autoantibody is anti-paranodal IgG.

[0098] As used herein, the phrase "total IgG level" or "total serum IgG level" refers to the serum endogenous IgG concentration, e.g., as it appears in a patient or in a patient's biological sample (e.g., a blood sample).

[0099] As used herein, the phrase "level of at least one autoantibody" refers to the serum endogenous concentration of at least one autoantibody, e.g., as present in a patient or a biological sample from a patient.

[0100] As used herein, the phrase "level of at least one IgG" refers to the serum endogenous concentration of at least one IgG, e.g., as present in a patient or a biological sample from a patient. In some embodiments, the at least one IgG comprises a pathogenic IgG. In some embodiments, the at least one IgG comprises a serum IgG1. In some embodiments, the at least one IgG comprises a serum IgG2. In some embodiments, the at least one IgG comprises a serum IgG3. In some embodiments, the at least one IgG comprises a serum IgG4.

[0101] As used herein, the terms "about" or "approximately" in the context of numerical values ​​and ranges refer to a value or range that is close to or approximates the stated value or range and ensures that the example can be performed as intended, as would be apparent to one of ordinary skill in the art from the teachings provided herein. These terms also encompass variations in values ​​due to systematic error. In some embodiments, "about" or "approximately" refers to ±10% of the numerical amount.

[0102] In some embodiments, a therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment is the amount required to reduce the adjusted Inflammatory Neuropathy Causes and Treatment (Adj INCAT) score in patients with CIDP and / or in samples obtained from patients with CIDP. The Adj INCAT disability score is a measure of activity limitation and is composed of two components: an upper extremity score and a lower extremity score. Depending on the degree of disability in the patient's upper and lower extremities, each component is assigned a score from 0 to 5, resulting in a total INCAT score ranging from 0 to 10. In some embodiments, a therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment is the amount required to reduce a patient's Adj INCAT score by at least 1 point, at least 2 points, at least 3 points, at least 4 points, at least 5 points, at least 6 points, at least 7 points, at least 8 points, or at least 9 points compared to the level before treatment with the anti-FcRn antibody or antigen-binding fragment. In some embodiments, a therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment is the amount required to reduce a patient's Adj INCAT score by 1 point, 2 points, 3 points, 4 points, 5 points, 6 points, 7 points, 8 points, 9 points, or 10 points compared to the level before treatment with the anti-FcRn antibody or antigen-binding fragment.

[0103] In various embodiments of the methods of treatment and uses disclosed herein, the antibody or antigen-binding fragment is administered to the patient in a fixed dose. In various embodiments of the methods of treatment and uses disclosed herein, the antibody or antigen-binding fragment is administered to the patient in a weight-based dose, i.e., a dose that depends on the patient's weight. In various embodiments of the methods of treatment and uses disclosed herein, the antibody or antigen-binding fragment is administered to the patient in a body surface area-based dose, i.e., a dose that depends on the patient's body surface area (BSA). In various embodiments, the dose administered to the patient comprises a therapeutically effective amount of the antibody or antigen-binding fragment.

[0104] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 170 mg to about 1500 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 300 mg to about 800 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 170 mg, about 200 mg, about 250 mg, about 255 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, about 1200 mg, about 1250 mg, about 1300 mg, about 1350 mg, about 1400 mg, about 1450 mg, or about 1500 mg, for example, once weekly or once every two weeks.

[0105] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 170 mg to about 300 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, or about 300 mg.

[0106] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 300 mg to about 500 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, about 400 mg, about 410 mg, about 420 mg, about 430 mg, about 440 mg, about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg, or about 500 mg.

[0107] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 300 mg to about 400 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, about 350 mg, about 360 mg, about 370 mg, about 380 mg, about 390 mg, or about 400 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 320 mg, about 330 mg, about 340 mg, about 350 mg, or about 360 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 340 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient once a week or once every two weeks at a dose of about 340 mg. In some embodiments, the antibody or antigen-binding fragment is administered to the patient once a week at a dose of about 340 mg. In some embodiments, the antibody or antigen-binding fragment is administered to the patient as a single subcutaneous injection once a week at a dose of about 340 mg. In some embodiments, the antibody or antigen-binding fragment is administered to the patient once a week at a dose of about 340 mg for at least two weeks (e.g., 2, 3, 4, 5, 6, 7, 8, 10, 12, or more weeks). In some embodiments, the antibody or antigen-binding fragment is administered to the patient once a week at a dose of about 340 mg for at least four weeks. In some embodiments, the antibody or antigen-binding fragment is administered to the patient once a week at a dose of about 340 mg for at least seven weeks. In some embodiments, the antibody or antigen-binding fragment is administered to the patient once a week at a dose of about 340 mg for at least 12 weeks.

[0108] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 500 mg to about 700 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 500 mg, about 510 mg, about 520 mg, about 530 mg, about 540 mg, about 550 mg, about 560 mg, about 570 mg, about 580 mg, about 590 mg, about 600 mg, about 610 mg, about 620 mg, about 630 mg, about 640 mg, about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, or about 700 mg.

[0109] In some embodiments, the antibody or antigen-binding fragment is administered to the patient at a dose of about 650 mg to about 750 mg. In some embodiments, the antibody or antigen-binding fragment is administered to the patient at a dose of about 650 mg, about 660 mg, about 670 mg, about 680 mg, about 690 mg, about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, or about 750 mg. In some embodiments, the antibody or antigen-binding fragment is administered to the patient at a dose of about 660 mg, about 670 mg, about 680 mg, about 690 mg, or about 700 mg. In some embodiments, the antibody or antigen-binding fragment is administered to the patient at a dose of about 680 mg. In some embodiments, the antibody or antigen-binding fragment is administered to the patient weekly or biweekly at a dose of about 680 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 680 mg once per week. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 680 mg by at least two (e.g., two) consecutive subcutaneous injections once per week. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 680 mg once per week for at least two weeks (e.g., 2, 3, 4, 5, 6, 7, 8, 10, 12, or more weeks). In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 680 mg once per week for at least four weeks. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 680 mg once per week for at least seven weeks. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 680 mg once per week for at least 12 weeks.

[0110] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 700 mg to about 900 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 700 mg, about 710 mg, about 720 mg, about 730 mg, about 740 mg, about 750 mg, about 760 mg, about 765 mg, about 770 mg, about 780 mg, about 790 mg, about 800 mg, about 810 mg, about 820 mg, about 830 mg, about 840 mg, about 850 mg, about 860 mg, about 870 mg, about 880 mg, about 890 mg, or about 900 mg.

[0111] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 900 mg to about 1100 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 900 mg, about 910 mg, about 920 mg, about 930 mg, about 940 mg, about 950 mg, about 960 mg, about 970 mg, about 980 mg, about 990 mg, about 1000 mg, about 1010 mg, about 1020 mg, about 1030 mg, about 1040 mg, about 1050 mg, about 1060 mg, about 1070 mg, about 1080 mg, about 1090 mg, or about 1100 mg.

[0112] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1100 mg to about 1300 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1100 mg, about 1110 mg, about 1120 mg, about 1130 mg, about 1140 mg, about 1150 mg, about 1160 mg, about 1170 mg, about 1180 mg, about 1190 mg, about 1200 mg, about 1210 mg, about 1220 mg, about 1230 mg, about 1240 mg, about 1250 mg, about 1260 mg, about 1270 mg, about 1280 mg, about 1190 mg, or about 1300 mg.

[0113] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1300 mg to about 1500 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1300 mg, about 1310 mg, about 1320 mg, about 1330 mg, about 1340 mg, about 1350 mg, about 1360 mg, about 1370 mg, about 1380 mg, about 1390 mg, about 1400 mg, about 1410 mg, about 1420 mg, about 1430 mg, about 1440 mg, about 1450 mg, about 1460 mg, about 1470 mg, about 1480 mg, about 1490 mg, or about 1500 mg.

[0114] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1 mg to about 2000 mg per kg of body weight. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1 mg to about 200 mg, about 200 mg to about 400 mg, about 400 mg to about 600 mg, about 600 mg to about 800 mg, about 800 mg to about 1000 mg, about 1000 mg to about 1200 mg, about 1200 mg to about 1400 mg, about 1400 mg to about 1600 mg, about 1600 mg to about 1800 mg, or about 1800 mg to about 2000 mg per kg of body weight. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1 mg to about 200 mg per kg of body weight. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, or about 200 mg per kg of body weight. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1 mg to about 40 mg per kg of body weight. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1 mg, about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, or about 40 mg per kg of body weight.

[0115] The antibody or antigen-binding fragment may be administered to a patient one or more times, either as a single formulation or in combination with one or more additional therapeutic agents. In some embodiments, the antibody or antigen-binding fragment is administered a single time. In some embodiments, the antibody or antigen-binding fragment is administered multiple times. The interval between doses may be, for example, daily, weekly, every two weeks, monthly, or yearly. The intervals may also be irregular, for example, based on measuring the antibody or antigen-binding fragment in the patient to maintain relatively constant blood levels of the antibody or antigen-binding fragment, or based on measuring the levels of at least one autoantibody and / or pathogenic antibody (e.g., at least one IgG) to maintain reduced levels to provide the desired therapeutic or prophylactic effect, based on measuring total serum IgG levels to maintain reduced levels of total serum IgG to provide the desired therapeutic or prophylactic effect, and / or based on measuring hemoglobin levels to maintain increased hemoglobin levels to provide the desired therapeutic or prophylactic effect. In another embodiment, the antibody or antigen-binding fragment may be administered as a sustained-release formulation, in which case less frequent administration is required. The dosage and frequency will vary depending on the half-life of the antibody or antigen-binding fragment in the patient. The dosage and frequency will also vary depending on whether the treatment is prophylactic or therapeutic. In prophylactic applications, relatively low doses are administered at relatively infrequent intervals over an extended period of time. Some patients may continue treatment for the rest of their lives. In therapeutic applications, relatively high doses are administered intermittently at relatively short intervals until the progression of the disease is suppressed or halted, and optionally, until the patient shows partial or complete improvement in one or more symptoms of the disease. Thereafter, the patient may be administered lower doses, for example, as a prophylactic treatment.

[0116] In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient one or more times over a period of about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 ​​months, 52 months, 60 months, or more.

[0117] In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to a patient once in a single dose.

[0118] In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once a week. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once a week for at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 12 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 40 weeks, at least 50 weeks, at least 60 weeks, at least 70 weeks, at least 76 weeks, at least 80 weeks, or more. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once a week for 6 to 76 weeks, or any period therebetween. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once a week for at least 2 weeks, at least 3 weeks, at least 4 weeks, or at least 6 weeks. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once a week for at least 4 weeks. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once a week for at least 7 weeks. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once a week for at least 12 weeks. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once a week for at least 24 weeks. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once a week for at least 52 weeks. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once a week until sufficient to treat, prevent, reduce the severity of, delay the onset of, and / or reduce the risk of onset of one or more symptoms of CIDP.

[0119] In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once a week as a single (i.e., one) subcutaneous injection. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once a week in two or more consecutive subcutaneous injections (e.g., two consecutive subcutaneous injections). As used herein, the term "sequentially," as used in the context of subcutaneous injections (or other routes of administration), means that two or more subcutaneous injections are administered consecutively, but within a time period sufficiently close enough to provide the desired therapeutic or prophylactic effect. In some embodiments, the consecutive subcutaneous injections are administered within about 30 seconds, about 1 minute, about 2 minutes, about 5 minutes, about 10 minutes, about 30 minutes, about 1 hour, about 2 hours, or about 5 hours of each other.

[0120] In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once every two weeks (every other week). In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once every two weeks for at least 2 weeks, at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, at least 12 weeks, at least 20 weeks, at least 24 weeks, at least 30 weeks, at least 40 weeks, at least 50 weeks, at least 60 weeks, at least 70 weeks, at least 76 weeks, at least 80 weeks, or more. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once every two weeks for 6 to 76 weeks, or any period therebetween. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once every two weeks for at least 12 weeks. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient weekly for at least 12 weeks. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient weekly for at least 24 weeks. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient weekly for at least 52 weeks. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient weekly for up to 24 weeks. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient weekly for up to 52 weeks. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient weekly in an amount sufficient to treat or prevent, reduce the severity, delay the onset, or reduce the risk of onset of one or more symptoms of CIDP. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient weekly as a single subcutaneous injection. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient weekly in two or more consecutive subcutaneous injections.

[0121] In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient monthly. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient monthly for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 18 months, at least 24 months, at least 30 months, at least 36 months, or more. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient monthly until sufficient to treat or prevent, reduce the severity, delay the onset, and / or reduce the risk of developing one or more symptoms of CIDP. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient monthly as a single subcutaneous injection. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient monthly as two or more consecutive subcutaneous injections.

[0122] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, the therapeutically effective amount of the antibody or antigen-binding fragment is about 170 mg to about 1500 mg, administered in a single dose. More specifically, in some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 170 mg to about 300 mg, administered in a single dose. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 300 mg to about 500 mg, administered in a single dose. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 500 mg to about 700 mg, administered in a single dose. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 700 mg to about 900 mg, administered in a single dose. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 900 mg to about 1100 mg, administered in a single dose. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 1100 mg to about 1300 mg administered once as a single dose. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 1300 mg to about 1500 mg administered once as a single dose.

[0123] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, the therapeutically effective amount of the antibody or antigen-binding fragment is about 300 mg to about 800 mg, administered in a single dose. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 300 mg to about 400 mg, administered in a single dose. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 340 mg, administered in a single dose. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 450 mg to about 550 mg, administered in a single dose. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 500 mg, administered in a single dose. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 700 mg to about 800 mg, administered in a single dose. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 765 mg, administered in a single dose. In some embodiments, the treatment reduces the patient's total serum IgG levels by at least about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50%. In some embodiments, the treatment reduces the patient's total serum IgG levels by at least about 25%. In some embodiments, the treatment reduces the patient's total serum IgG levels by at least about 35%. In some embodiments, the treatment reduces the patient's total serum IgG levels by at least about 45%. In some embodiments, the maximum decrease in the patient's total serum IgG levels occurs between about 5 days and about 20 days after administration of the antibody or antigen-binding fragment, or a pharmaceutical composition comprising the antibody or antigen-binding fragment. In some embodiments, the maximum decrease in the patient's total serum IgG levels occurs between about 8 days and about 15 days after administration of the antibody or antigen-binding fragment, or a pharmaceutical composition comprising the antibody or antigen-binding fragment. In some embodiments, the maximum decrease in total serum IgG levels occurs after about 3 to about 5 administrations (e.g., about 4 administrations) of the antibody or antigen-binding fragment, or pharmaceutical composition comprising the antibody or antigen-binding fragment. In some embodiments, the treatment increases the patient's hemoglobin levels by at least about 5%, about 10%, about 15%, or about 20% (e.g., about 5% to about 30%).In some embodiments, the treatment increases the patient's hemoglobin level by at least about 10% (e.g., about 10% to about 15%). In some embodiments, the treatment increases the patient's hemoglobin level by at least about 20% (e.g., about 20% to about 25%). In some embodiments, the treatment increases the patient's hemoglobin level by more than about 20% (e.g., about 25%, about 30%, or more).

[0124] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, the therapeutically effective amount of the antibody or antigen-binding fragment is about 170 mg to about 1500 mg and is administered once per week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 170 mg to about 300 mg and is administered once per week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 300 mg to about 500 mg and is administered once per week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 500 mg to about 700 mg and is administered once per week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 700 mg to about 900 mg and is administered once per week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 900 mg to about 1100 mg and is administered once per week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 1100 mg to about 1300 mg administered once per week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 1300 mg to about 1500 mg administered once per week.

[0125] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, the therapeutically effective amount of the antibody or antigen-binding fragment is about 300 mg to about 800 mg and is administered once per week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 300 mg to about 400 mg and is administered once per week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 340 mg and is administered once per week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 650 mg to about 750 mg and is administered once per week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 680 mg and is administered once per week. In some embodiments, the treatment reduces the patient's total serum IgG levels by at least about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, or about 80%. In some embodiments, the treatment reduces the patient's total serum IgG levels by at least about 60%. In some embodiments, the treatment reduces the patient's total serum IgG level by at least about 70%. In some embodiments, the treatment reduces the patient's total serum IgG level by at least about 80%. In some embodiments, the maximum decrease in the patient's total serum IgG level occurs between about 20 and about 30 days after administration of the antibody or antigen-binding fragment, or a pharmaceutical composition comprising the antibody or antigen-binding fragment. In some embodiments, the maximum decrease in the patient's total serum IgG level occurs about 24 days after administration of the antibody or antigen-binding fragment, or a pharmaceutical composition comprising the antibody or antigen-binding fragment. In some embodiments, the maximum decrease in the patient's total serum IgG level occurs after about 3 to about 5 administrations (e.g., about 4 administrations) of the antibody or antigen-binding fragment, or a pharmaceutical composition comprising the antibody or antigen-binding fragment. In some embodiments, the treatment increases the patient's hemoglobin level by at least about 5%, about 10%, about 15%, or about 20% (e.g., about 5% to about 30%). In some embodiments, the treatment increases the patient's hemoglobin level by more than about 20%. In some embodiments, treatment increases a patient's hemoglobin levels by at least about 10% (e.g., about 10% to about 15%) after about one or two weeks of weekly dosing (e.g., 680 mg once a week).In some embodiments, treatment increases a patient's hemoglobin level by at least about 20% (e.g., about 20% to about 25%) after about one or two weeks of weekly administration (e.g., 680 mg or 340 mg weekly). In some embodiments, the increase in a patient's hemoglobin level (e.g., an increase of about 10%, about 20%, or more) is maintained throughout all or part of the treatment period. In some embodiments, the increase in a patient's hemoglobin level (e.g., an increase of about 10%, about 20%, or more) is maintained for at least four weeks (e.g., at least four, six, eight, ten, twelve, or more weeks).

[0126] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, the therapeutically effective amount of the antibody or antigen-binding fragment is about 170 mg to about 1500 mg and is administered once every two weeks. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 300 mg to about 800 mg and is administered once every two weeks. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 170 mg to about 300 mg and is administered once every two weeks. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 300 mg to about 500 mg and is administered once every two weeks. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 500 mg to about 700 mg and is administered once every two weeks. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 700 mg to about 900 mg and is administered once every two weeks. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 900 mg to about 1100 mg and is administered once every two weeks. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 1100 mg to about 1300 mg and is administered once every two weeks. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 1300 mg to about 1500 mg and is administered once every two weeks.

[0127] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, the therapeutically effective amount of the antibody or antigen-binding fragment is about 170 mg to about 1500 mg and is administered once a month. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 300 mg to about 800 mg and is administered once a month. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 170 mg to about 300 mg and is administered once a month. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 300 mg to about 500 mg and is administered once a month. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 500 mg to about 700 mg and is administered once a month. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 700 mg to about 900 mg and is administered once a month. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 900 mg to about 1100 mg and is administered once a month. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 1100 mg to about 1300 mg administered once a month. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 1300 mg to about 1500 mg administered once a month.

[0128] In some embodiments of the methods, uses, and compositions disclosed herein, the therapeutically effective amount of the antibody or antigen-binding fragment is about 340 mg or about 680 mg and is administered once a week. In some embodiments, the antibody or antigen-binding fragment is administered subcutaneously.

[0129] In some embodiments, treatment with an antibody or antigen-binding fragment administered once weekly at a dose of about 340 mg or about 680 mg reduces total serum IgG levels in a patient and / or sample from the patient by at least about 40% (e.g., about 40% to about 50%) after about one or two weeks of weekly administration, compared to the total serum IgG levels in the patient and / or sample before treatment. In some embodiments, treatment with an antibody or antigen-binding fragment administered once weekly at a dose of about 340 mg or about 680 mg reduces total serum IgG levels in a patient and / or sample from the patient by at least about 60% (e.g., about 60% to about 70%) after about three weeks of weekly administration, compared to the total serum IgG levels in the patient and / or sample before treatment. In some embodiments, treatment with an antibody or antigen-binding fragment administered once weekly at a dose of about 340 mg or about 680 mg reduces total serum IgG levels in a patient and / or a sample from the patient by at least about 70% (e.g., about 70% to about 80%) after about 5 weeks of weekly administration, compared to total serum IgG levels in the patient and / or a sample from the patient before treatment. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is about 680 mg and administered once weekly. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is about 680 mg and administered once weekly for at least 2 weeks (e.g., 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 10 weeks, 12 weeks, 24 weeks, 48 ​​weeks, 52 weeks, or more). In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is about 340 mg and administered once weekly. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 680 mg administered once a week for at least 2 weeks (e.g., 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 52, or more weeks).

[0130] In some embodiments, the antibody or antigen-binding fragment is administered to the patient in one or more doses (e.g., two or more different doses). For example, in some embodiments, the antibody or antigen-binding fragment is administered to the patient in two different doses, e.g., at least one high dose followed by at least one low dose. The high dose (e.g., the higher of the two different doses) may be referred to herein as the "induction" dose, i.e., the dose that is capable of reducing the level of at least one autoantibody and / or pathogenic antibody (e.g., at least one IgG) in the patient and / or in a sample from the patient. The low dose (e.g., the lower of the two different doses) may be referred to herein as the "maintenance" dose, i.e., the dose that is capable of maintaining a reduced level of at least one autoantibody and / or pathogenic antibody (e.g., at least one IgG) in the patient and / or in a sample from the patient after at least one induction dose of the antibody or antigen-binding fragment (e.g., about 20-80% of the pre-treatment (pre-induction dose) level). In some embodiments, the maintenance dose maintains the level of at least one autoantibody and / or pathogenic antibody (e.g., at least one IgG) in the patient and / or in a sample from the patient at about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, or about 80% of the pre-treatment (pre-induction dose) level.

[0131] In some embodiments, the antibody or antigen-binding fragment is administered to the patient in two or more doses (e.g., three or more different doses). For example, in some embodiments, the antibody or antigen-binding fragment is administered to the patient in three different doses, for example, at least one high dose (e.g., 680 mg) administered over a period of time, followed by at least one low dose (e.g., 340 mg) administered over a period of time, and then a third dose administered over a period of time. In some embodiments, the third dose administered is the same as the high dose administered (e.g., 680 mg). In some embodiments, the third dose administered is the same as the low dose administered (e.g., 340 mg). In some embodiments, the third dose administered is about 340 mg or 680 mg per dose. In some embodiments, if the patient does not relapse during the second low dose administration period, the patient is administered a low dose (e.g., 340 mg) during the third dose period. In some embodiments, if a patient relapses during the second lower dose period, the patient is administered a higher dose (e.g., 680 mg, e.g., for at least 4 weeks, at least 12 weeks, or at least 28 weeks) followed by a lower dose (e.g., 340 mg) as part of a third dose period, which in some embodiments is administered subcutaneously once weekly.

[0132] In some embodiments, the antibody or antigen-binding fragment is administered to a patient in two or more doses, wherein the patient is in a relapsed state. In some embodiments, the patient is in a relapsed state after treatment with at least one maintenance dose. In some embodiments, the relapsed patient is treated with a dose of about 680 mg followed by a dose of about 340 mg. In some embodiments, the relapsed patient is treated with a dose of about 680 mg administered subcutaneously once weekly, for example, for four weeks or at least four weeks, followed by treatment with a dose of about 340 mg administered subcutaneously once weekly.

[0133] In some embodiments, the induction dose and the maintenance dose are administered in alternating fashion, e.g., a patient may receive an induction dose for a first period, followed by a maintenance dose for a first period, followed by an induction dose for a second period, optionally followed by a maintenance dose for a second period. In some embodiments, the cycle of induction and maintenance doses (where an induction dose for a period, followed by a maintenance dose for a period) is repeated 1, 2, 3, 4, 5, 6, 7, or 10 times. In some embodiments, the cycle of induction and maintenance doses is repeated every about 3 months, about 6 months, about 12 months, about 15 months, about 18 months, about 24 months, or more.

[0134] In some embodiments, at least one high dose and / or induction dose is about 680 mg per dose or more (e.g., about 700 mg per dose, about 720 mg per dose, about 750 mg per dose, or more). In some embodiments, at least one high dose and / or induction dose is about 1 dose, about 2 doses, about 3 doses, about 4 doses, or about 5 doses of about 680 mg per dose or more (e.g., about 700 mg per dose, about 720 mg per dose, about 750 mg per dose, or more). In some embodiments, at least one high dose and / or induction dose is about 3 doses of about 680 mg per dose or more (e.g., about 700 mg per dose, about 720 mg per dose, about 750 mg per dose, or more).

[0135] In some embodiments, at least one high dose and / or induction dose is administered to the patient once, once a week, once every two weeks, or once a month. In some embodiments, at least one high dose and / or induction dose is administered to the patient intravenously. In some embodiments, at least one high dose and / or induction dose is administered to the patient subcutaneously. In some embodiments, each high dose is administered to the patient by one or more subcutaneous injections. In some embodiments, each high dose is administered to the patient by two consecutive subcutaneous injections.

[0136] In some embodiments, at least one lower dose and / or maintenance dose is about 340 mg per dose. In some embodiments, at least one lower dose and / or maintenance dose is about 300 mg per dose. In some embodiments, at least one lower dose and / or maintenance dose is about 340 mg per dose, about 1 dose, about 2 doses, about 3 doses, about 4 doses, or about 5 doses. In some embodiments, at least one lower dose and / or maintenance dose is about 300 mg per dose, or about 3 doses of about 340 mg per dose. In some embodiments, at least one lower dose and / or maintenance dose is administered to a patient once, once weekly, once every two weeks, or once monthly. In some embodiments, at least one lower dose and / or maintenance dose is administered to a patient subcutaneously. In some embodiments, each lower dose is administered to a patient by one or more subcutaneous injections. In some embodiments, each sub-dose is administered to the patient in a single subcutaneous injection.

[0137] In various embodiments, the present disclosure also provides kits for use in the therapeutic applications described herein. In various embodiments, the present disclosure provides kits comprising an anti-FcRn antibody or antigen-binding fragment thereof for use in treating or preventing CIDP. In various embodiments, the kit further comprises one or more additional components, including, but not limited to, instructions for use, other therapeutic modalities, e.g., one or more additional therapeutic modalities (e.g., one or more standard of care modalities), a device, container, or other material for preparing the antibody or antigen-binding fragment for therapeutic administration, a pharmaceutically acceptable carrier (e.g., excipient), and a device, container, or other material for administering the antibody or antigen-binding fragment to a patient. In some embodiments, the kit comprises a pre-filled syringe containing a single dose of the antibody or antigen-binding fragment thereof (e.g., a dosage described herein) and instructions for use. The instructions for use can include guidance for therapeutic application, including, for example, a suggested dose and / or method of administration, in patients with or suspected of having CIDP. In various embodiments, the kit includes an anti-FcRn antibody or antigen-binding fragment thereof and instructions for therapeutic use, e.g., using the antibody or antigen-binding fragment to treat or prevent CIDP in a patient. In various embodiments, the kit further includes at least one additional therapeutic agent (e.g., for administration in combination with the antibody or antigen-binding fragment). In various embodiments, the antibody or antigen-binding fragment is formulated as a pharmaceutical composition.

[0138] In some embodiments, the anti-FcRn antibody or antigen-binding fragment is prepared by expression and purification using recombinant DNA methods. In some embodiments, polynucleotide sequences encoding the variable regions of the antibody or antigen-binding fragment are prepared by expression in separate host cells or co-expression in a single host cell. Exemplary polynucleotides encoding the VH and VL, and heavy and light chains of anti-FcRn antibodies are shown in Tables 4 and 5, respectively.

[0139] [Table 4-1]

[0140] [Table 4-2]

[0141] [Table 4-3]

[0142] [Table 5-1]

[0143] [Table 5-2]

[0144] [Table 5-3]

[0145] As used herein, the term "recombinant vector" refers to an expression vector capable of expressing a protein of interest in a suitable host cell. This term encompasses a DNA construct containing the necessary regulatory elements operably linked to express a nucleic acid insert.

[0146] As used herein, the term "operably linked" refers to a nucleic acid expression control sequence that is functionally linked to a nucleic acid sequence encoding a protein of interest so as to perform its general function. Operable linkage with a recombinant vector can be achieved using recombinant gene technology well known in the art, and site-specific DNA cleavage and ligation can be easily achieved using enzymes commonly known in the art.

[0147] Suitable expression vectors can include expression regulatory elements such as promoters, operators, initiation codons, termination codons, polyadenylation signals, and enhancers, as well as signal sequences for membrane targeting or secretion. The initiation and termination codons are typically considered part of the nucleotide sequence encoding the immunogenic target protein and are necessary for the gene construct to function in the administered individual and must be in frame with the coding sequence. Promoters can typically be constitutive or inducible. Prokaryotic promoters include, but are not limited to, lac, tac, T3, and T7 promoters. Eukaryotic promoters include, but are not limited to, the simian virus 40 (SV40) promoter, mouse mammary tumor virus (MMTV) promoter, human immunodeficiency virus (HIV) promoter (e.g., the HIV long terminal repeat (LTR) promoter), Moloney virus promoter, cytomegalovirus (CMV) promoter, Epstein-Barr virus (EBV) promoter, Ruth Sacoma virus (RSV) promoter, and promoters derived from human genes such as human β-actin, human hemoglobin, human muscle creatine, and human metallothionine. Expression vectors can contain a selectable marker that allows for the selection of host cells containing the vector. Genes encoding products that confer a selectable phenotype, such as drug resistance, auxotrophy, resistance to toxic substances, or expression of surface proteins, can be used as common selectable markers. Only cells expressing the selectable marker survive in an environment treated with a selective agent, allowing for the selection of transformed cells. Furthermore, replicable expression vectors can contain an origin of replication, i.e., a specific nucleic acid sequence that initiates replication. Recombinant expression vectors that can be used include a variety of vectors, such as plasmids, viruses, and cosmids. The type of recombinant vector is not limited, and the recombinant vector can function to express a desired gene and produce a desired protein in various host cells, such as prokaryotic and eukaryotic cells.In some embodiments, a vector is used that has a strong expression ability together with a promoter that exhibits strong activity, and that can produce large amounts of a foreign protein similar to the native protein.

[0148] Various expression host or vector combinations can be used to express anti-FcRn antibodies or antigen-binding fragments thereof. For example, expression vectors suitable for eukaryotic hosts include, but are not limited to, SV40, bovine papilloma virus, adenovirus, adeno-associated virus, cytomegalovirus, and retrovirus. Expression vectors that can be used in bacterial hosts include bacterial plasmids such as pET, pRSET, pBluescript, pGEX2T, pUC, c·l E1, pCR1, pBR322, pMB9, and their derivatives; broad-host-range plasmids such as RP4; phage DNA, represented by various phage lambda derivatives such as gt10, gt11, and NM989; and other DNA phages such as the M13 filamentous single-stranded DNA phage. Useful expression vectors for yeast cells include the 2µm plasmid and its derivatives. A useful vector for insect cells is pVL941.

[0149] In some embodiments, the recombinant vector is introduced into a host cell to form a transformant. Suitable host cells for use include prokaryotic cells such as Escherichia coli (E. c·i), Bacillus subtilis, Streptomyces sp., Pseudomonas sp., Proteus mirabilis, and Staphylococcus sp., fungi such as Aspergillus sp., yeasts such as Pichia pastoris, Saccharomyces cerevisiae, Schizosaccharomyces sp., and Neurospora crassa, and eukaryotic cells such as lower eukaryotic cells and other higher eukaryotic cells, such as insect cells.

[0150] In some embodiments, the host cells are derived from plants or animals (e.g., mammals), including, but not limited to, monkey kidney cells (COS7), NSO cells, SP2 / 0, Chinese hamster ovary (CHO) cells, W138, baby hamster kidney (BHK) cells, MDCK, myeloma cells, HuT 78 cells, and HEK293 cells. In some embodiments, CHO cells are used.

[0151] Transduction or transformation of host cells includes any method by which nucleic acid can be introduced into an organism, cell, tissue, or organ, and can be carried out using standard techniques known in the art, appropriate to the type of host cell, including, but not limited to, electroporation, protoplast fusion, calcium phosphate (CaPO) precipitation, calcium chloride (CaCl) precipitation, agitation with silicon carbide fibers, and Agrobacterium-, PEG-, dextran sulfate-, lipofectamine-, and desiccation / suppression-mediated transformation.

[0152] Anti-FcRn antibodies or antigen-binding fragments can be produced in large quantities by culturing transformants containing the recombinant vector in a nutrient medium. The medium and culture conditions used can be selected depending on the type of host cell. During cultivation, conditions such as temperature, medium pH, and culture time can be controlled to suit cell growth and large-scale protein production. Antibodies or antigen-binding fragments produced by the recombinant methods described herein can be collected from the medium or cell lysate and separated and purified using conventional biochemical separation techniques (Sambrook et al., Cellular Clone: ​​A Laboratory Manual, 2nd Ed., Spring Harbour Laboratory Press (1989); Deuscher, Guide to Protein Purification in Meth- and Enzyme-Lysics, Vol. 182, No. 1, Academic Press, Inc., San Diego, CA (1990)). These techniques include, but are not limited to, electrophoresis, centrifugation, gel filtration, precipitation, dialysis, chromatography (e.g., ion exchange chromatography, affinity chromatography, immunoadsorption chromatography, size exclusion chromatography, etc.), isoelectric focusing, and various variations and combinations thereof. In some embodiments, antibodies or antigen-binding fragments are separated and purified using Protein A.

[0153] Example The present disclosure will now be described in more detail with reference to examples. As will be apparent to those skilled in the art, these examples are for illustrative purposes only and are not to be construed as limiting the scope of the present disclosure.

[0154] Example 1: Clinical study of batoclimab treatment in CIDP This example describes a phase 2b, multicenter, randomized, quadruple-blind, placebo-controlled study of batoclimab treatment in adult participants with active CIDP. An overview of the clinical trial is shown in Figure 1. Approximately 277 patients will be enrolled.

[0155] Four cohorts (designated Cohort A, B, C, or D) were defined by whether patients received baseline CIDP treatment and met diagnostic criteria based on EAN / PNS criteria at screening (Cohorts A, B, and C) or clinical criteria (Cohort D). Cohort A: patients receiving immunoglobulin (IVIg or SCIg) therapy or PLEX; Cohort B: patients receiving chronic systemic corticosteroids (i.e., pulse or daily use); Cohort C: patients receiving untreated treatment (i.e., newly diagnosed patients or patients previously stable without treatment but currently experiencing disease worsening); and Cohort D: patients receiving immunoglobulin (IVIg or SCIg) therapy or PLEX who met clinical criteria for CIDP but did not meet full diagnostic criteria based on the EAN / PNS CIDP Diagnosis and Treatment Guidelines.

[0156] Batoclimab is formulated in a 340 mg prefilled syringe (170 mg / mL, 2 mL) containing 340 mg batoclimab, 25.16 mg L-histidine hydrochloride, 12.416 mg L-histidine, 42.14 mg L-arginine hydrochloride, and 0.4 mg polysorbate 20 in water. The placebo formulation contains the same buffer and surfactant (but no batoclimab).

[0157] Participants in Cohorts A, B, or D will enter a washout period (wash·ut peri·d) of up to 12 weeks, during which standard of care will be discontinued or tapered. Participants in Cohorts A, B, or D who have not progressed by the end of this washout period (Week 0) will be withdrawn from the study. Participants who meet the progression criteria and those in Cohort C who do not enter the washout period will be randomly assigned to receive 680 mg or 340 mg of batoclimab subcutaneously once weekly during Period 1 (12 weeks). Non-responders who complete Period 1 will be withdrawn from the study after completing Week 12 and the subsequent 4-week follow-up visit. Period 1 non-responders who require protocol-prohibited rescue therapy before Week 12 can discontinue batoclimab and return to standard of care, and these participants are encouraged to remain in the study for safety follow-up (Safety F·ll·w-Up) through Week 12 and the follow-up visits.

[0158] During Phase 2 (up to 24 weeks), participants will be randomly assigned to receive either placebo or 340 mg of batoclimab subcutaneously once weekly. Participants who relapse during Phase 2 or complete Phase 2 without relapse will be eligible to participate in the long-term extension (L·ng-Term Extensi·n study). Phase 2 will be followed by a long-term extension (LTE) period (up to 52 weeks). During the LTE period, participants who relapse during Phase 2 will receive 680 mg of batoclimab subcutaneously once weekly for 4 weeks, followed by 340 mg of batoclimab subcutaneously once weekly. Participants in the LTE period who do not relapse during Phase 2 will receive 340 mg of batoclimab subcutaneously once weekly.

[0159] the purpose The primary objective of the study is to evaluate the efficacy of batoclimab compared with placebo in maintaining clinical response, as assessed by the adjusted Inflammatory Neuropathy Causes and Treatment (Adj INCAT) score, in participants receiving immunoglobulin (IVIg or SCIg) or plasma exchange (PLEX) for the treatment of CIDP at screening.

[0160] The secondary objectives were: (1) to evaluate the effectiveness of batoclimab compared to placebo in maintaining clinical response in participants receiving immunoglobulin (IVIg or SCIg) or PLEX for the treatment of CIDP at screening, (2) to evaluate the effectiveness of batoclimab compared to placebo in maintaining clinical response in participants receiving any CIDP treatment at screening, and (3) to evaluate the effectiveness of batoclimab compared to placebo in maintaining clinical response, regardless of prior CIDP treatment.

[0161] Inclusion criteria 1. Be over 18 years of age at the time of the screening visit.

[0162] 2. Meet the clinical diagnostic criteria for typical CIDP or one of the following CIDP subtypes: multifocal CIDP, focal CIDP, or motor CIDP, according to the EAN / PNS CIDP Diagnosis and Treatment Guidelines. The clinical criteria for typical CIDP and its subtypes are as follows (any one of the following criteria must be met): a. Classic CIDP: All of the following: - Progressive or recurrent, symmetrical weakness of proximal and distal muscles of the upper and lower extremities and sensory loss in at least two limbs (at any time during the course of the disease) - At least 8 weeks of progression - Absent or diminished tendon reflexes in all limbs b. CIDP subtype: Same as typical CIDP (tendon reflexes may be normal in unaffected limbs), except for one of the following: - Multifocal CIDP: documented sensory loss and a multifocal pattern of muscle weakness, typically asymmetric and upper limb predominant - Focal CIDP: loss of sensation and muscle weakness in only one limb - Motor CIDP: motor symptoms and signs without sensory impairment Cohorts A and B

[0163] 3. Have electrodiagnostic test results supporting a CIDP diagnosis according to the EAN / PNS CIDP diagnosis and treatment guidelines (meeting either criterion 3(a) or 3(b) below) a. Motor nerve conduction criteria strongly supportive of demyelination. b. Motor nerve conduction criteria weakly supportive of demyelination and two or more of the following additional diagnostic criteria: - Objective improvement on empirical treatment trials with immunoglobulin therapy, plasma exchange (PLEX), or corticosteroids. - Ultrasound or magnetic resonance imaging (MRI) supports the diagnosis of CIDP and shows nerve hypertrophy. - Cerebrospinal fluid (CSF) shows albuminocyte dissociation (i.e., elevated CSF protein levels [≥70 milligrams per deciliter (70 mg / dL) or ≥10 mg / dL for age if older than 60 years] and normal CSF white blood cell [WBC] levels). - Nerve biopsy has features supporting a diagnosis of CIDP, such as edema, demyelination, and / or onion bulb formation.

[0164] Applicable to Cohorts A and D only: 4. At the time of the screening visit, participants have been receiving immunoglobulin therapy (IVIg or SCIg) or PLEX for the treatment of CIDP for at least 3 months and are currently receiving it. Note: Participants receiving chronic systemic corticosteroids in conjunction with immunoglobulin therapy or PLEX are permitted only if their corticosteroid dose remains stable and is ≤10 mg / day of prednisolone / prednisone or equivalent during the washout period (Wash·ut) and participation in Periods 1 and 2. Participants taking other immunosuppressants are not excluded, but must discontinue these medications at the time of entering the washout period.

[0165] 5. Have a documented response to immunoglobulin therapy or PLEX prior to the lean visit (meeting any of the following criteria (a), (b), (c), or (d)): a. Treatment discontinuation (or dose or frequency reduction) trial of immunoglobulin therapy or PLEX within 5 years prior to the screening visit followed by documented worsening of symptoms. b. Requirement of therapy augmentation (i.e., increase in dose or frequency of immunoglobulin therapy or PLEX) within 12 months prior to the screening visit and documented improvement in signs and symptoms. c. After treatment initiation and initial adjustment, no therapy escalation was required (i.e., no increase in the dose or frequency of immunoglobulin therapy or PLEX was required, and no corticosteroids were added to the treatment regimen), and an INCAT score of 0 or 1 (or a clinical history consistent with an INCAT score of 0 or 1) was maintained. Note: Participants meeting criterion (c) must have an INCAT score of 0 or 1 at the screening visit. d. Has demonstrated documented improvement in an empirical treatment trial with immunoglobulin therapy or PLEX.

[0166] Applicable to Cohort B only: 6. At the time of the screening visit, the patient is receiving a chronic and stable dose of systemic corticosteroids for the treatment of CIDP (meeting either criterion (a) or (b) below): a. Receiving chronic oral corticosteroids equivalent to 20-40 mg / day of prednisolone / prednisone (including every other day or similar regimen) and willing to comply with dose reduction requests during the washout period. See reference below for participants receiving doses less than 20 mg / day. Reference: A stable dose is considered to be a daily fluctuation of 2.5 mg or less of prednisone or its equivalent for a period of 3 months or more prior to the screening visit. Note: Participants maintaining prednisolone / prednisone or equivalent at a dose less than 20 mg / day (including every other day or similar regimen) meet inclusion criteria 2(a) and 3(a) and may be considered for eligibility following consultation with the Sponsor's medical monitor. b. Receiving chronic pulse corticosteroid therapy defined as ≥100 mg / day prednisolone / prednisone equivalent (i.e., intravenous [IV] / intramuscular [IM] or oral [PO]) with a minimum interval of ≥3 weeks between pulse treatments and willingness to discontinue pulse treatment at the start of the washout period. Reference: A stable dose is considered to be repeated cycles requiring no dose adjustment to maintain disease control for a period of at least 3 months prior to the screening visit.

[0167] 7. Have a documented response to first-line standard treatment for CIDP (immunoglobulin therapy, corticosteroids, or PLEX) (meeting any of the following criteria (a), (b), (c), or (d)): a. Treatment discontinuation (or dose or frequency reduction) trial of immunoglobulin therapy, corticosteroids, or PLEX within 5 years prior to the screening visit followed by documented worsening of symptoms. b. Requirement of corticosteroid therapy augmentation (i.e., increase in corticosteroid dose or frequency) within 12 months prior to the screening visit and documented improvement in signs and symptoms. c. After treatment initiation and initial adjustment, no regimen augmentation (i.e., increase in corticosteroid dose or frequency) was required and an INCAT score of 0 or 1 (or a clinical history consistent with an INCAT score of 0 or 1) was maintained. Note: Participants meeting criterion (c) must have an INCAT score of 0 or 1 at the screening visit. d. Has demonstrated documented improvement on empirical treatment trials with immunoglobulin therapy, PLEX, or corticosteroids.

[0168] Applicable to Cohort C only: 8. According to the CIDP Diagnosis and Treatment Guidelines for EAN / PNS (van den Bergh et al., 2021), the diagnosis of CIDP is established by clinical criteria and motor nerve conduction criteria that strongly support demyelination (i.e., motor nerve conduction criteria that weakly support demyelination do not provide sufficient diagnostic evidence to support eligibility for Cohort C).

[0169] 9. Not currently receiving treatment for CIDP at the time of the screening visit (meeting either criterion (a) or (b) below): a. No prior treatment experience. b. History of treatment with immunoglobulin therapy (IVIg or SCIg), corticosteroids, or PLEX at least 3 months prior to the screening visit but within 24 months, after which treatment was discontinued.

[0170] 10. Documented evidence of clinical worsening of CIDP requiring treatment initiation or resumption within 3 months prior to the screening visit.

[0171] 11. INCAT score ≥ 2 at screening and Phase 1 baseline visits. Note: For participants with an INCAT score of 2 at the start of the study, that score must be attributed to a lower limb impairment score; for participants with an INCAT score of 3 or higher at the start of the study, there are no additional upper or lower limb requirements.

[0172] 12. Other inclusion criteria are defined in the protocol.

[0173] Exclusion criteria 1. Patients with immunoglobulin M (IgM) paraproteinemia with or without anti-myelin-associated glycoprotein antibodies.

[0174] 2. Patients with distal CIDP or sensory CIDP, or suspected diagnosis of autoimmune nodopathy according to the EAN / PNS CIDP diagnosis and treatment guidelines.

[0175] 3. If you have polyneuropathy due to causes other than CIDP, including but not limited to: a. Multifocal motor neuropathy b. Hereditary demyelinating neuropathy c. Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes syndrome (i.e., POEMS) d. Lumbar plexus disorder e. Systemic diseases, including vitamin deficiency syndromes and edematous neuropathy f. Drug- or toxin-induced 4. If you have diabetes mellitus (DM) and meet any of the following criteria: a. When the diagnosis of DM precedes the diagnosis of CIDP b. Daily insulin therapy was required c. DM duration is 5 years or more d. If there is evidence of microvascular complications of DM, including: e. Retinopathy or nephropathy

[0176] 5. If there is a history of myelopathy or evidence of central demyelination.

[0177] 6. If receiving chronic oral corticosteroid monotherapy at a dose greater than 40 mg / day of prednisolone / prednisone or equivalent at the time of the screening visit.

[0178] 7. Receiving chronic oral corticosteroids at a dose greater than 10 mg / day of prednisone or its equivalent in combination with immunoglobulin therapy or PLEX at the time of the screening visit.

[0179] 8. Other exclusion criteria are defined in the protocol.

[0180] endpoint The primary endpoint was the proportion of participants who remained relapse-free at week 36, where "relapse" was defined as a worsening (increase) of ≥1 point in the Adj INCAT score compared to Period 2 baseline at any time during Period 2, with that worsening persisting at the 1-week follow-up visit.

[0181] Secondary endpoints include: - Phase 2 / Cohort A: Time from Phase 2 baseline to first relapse o Change from baseline to week 36 in Period 2: Adj INCAT score · Inflammatory Rasch Construct Global Disability Scale (I-RODS) · Average grip strength Medical Research Council (MRC) total score Total Neurological Limitation Scale (ONLS) - Phase 2 / Combining Cohorts A and B: o Change from baseline to week 36 in Period 2: Adj INCAT score I-RODS · Average grip strength MRC Total Score ONLS - Phase 2 / Combined Cohorts A, B and C: o Percentage of participants who remained relapse-free at week 36 Although the present disclosure has been described in detail with reference to certain features, those skilled in the art will appreciate that this description is for illustrative purposes only and is not intended to limit the scope of the present disclosure, and therefore the true scope of the present disclosure is defined by the appended claims and their equivalents.

Claims

1. 1. A method of treating CIDP, comprising administering to a patient in need of treatment thereof a first therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment is (a) a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence set forth in SEQ ID N·:27, an HCDR2 comprising the amino acid sequence set forth in SEQ ID N·:28, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID N·:29, and a light chain variable region comprising an LCDR1 comprising the amino acid sequence set forth in SEQ ID N·:30, an LCDR2 comprising the amino acid sequence set forth in SEQ ID N·:31, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID N·:32; or (b) a heavy chain variable region comprising an HCDR1 having the amino acid sequence shown in SEQ ID N:49, an HCDR2 having the amino acid sequence shown in SEQ ID N:22, and an HCDR3 having the amino acid sequence shown in SEQ ID N:23, and a light chain variable region comprising an LCDR1 having the amino acid sequence shown in SEQ ID N:50, an LCDR2 having the amino acid sequence shown in SEQ ID N:25, and an LCDR3 having the amino acid sequence shown in SEQ ID N:

26.

2. The antibody or antigen-binding fragment (a) a heavy chain variable region comprising an amino acid sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N:6, and a light chain variable region comprising an amino acid sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N:16; or (b) a heavy chain variable region comprising an amino acid sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N:51, and a light chain variable region comprising an amino acid sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the sequence set forth in SEQ ID N:

52.

3. The antibody or antigen-binding fragment (a) a heavy chain variable region comprising the sequence set forth in SEQ ID N:6 and a light chain variable region comprising the sequence set forth in SEQ ID N:16; or The method of claim 1, characterized in that (b) the heavy chain variable region comprises the sequence shown in SEQ ID N:51, and the light chain variable region comprises the sequence shown in SEQ ID N:

52.

4. The method according to any one of claims 1 to 3, wherein the antibody or antigen-binding fragment binds to FcRn with a KD (dissociation constant) of 0.01 nM to 2 nM at pH 6.0 or pH 7.

4.

5. 5. The method of claim 4, wherein the KD is measured by surface plasmon resonance (SPR).

6. The method of any one of claims 1 to 5, wherein the antibody or antigen-binding fragment is administered subcutaneously.

7. The method of any one of claims 1 to 6, wherein the antibody or antigen-binding fragment is administered once weekly.

8. The method of any one of claims 1 to 7, wherein the first therapeutically effective amount of the antibody or antigen-binding fragment is 300 mg to 500 mg.

9. 9. The method of claim 8, wherein the first therapeutically effective amount of the antibody or antigen-binding fragment is 340 mg.

10. The method of any one of claims 1 to 7, wherein the first therapeutically effective amount of the antibody or antigen-binding fragment is 500 mg to 700 mg.

11. 11. The method of claim 10, wherein the first therapeutically effective amount of the antibody or antigen-binding fragment is 680 mg.

12. The method of any one of claims 1 to 11, wherein the first therapeutically effective dose of the antibody or antigen-binding fragment is administered for 12 weeks.

13. The method of any of claims 1 to 12, further comprising administering to the patient a second therapeutically effective amount of the antibody or antigen-binding fragment.

14. 12. The method of claim 11, wherein the second therapeutically effective amount is 340 mg.

15. 15. The method of claim 13 or 14, wherein the second therapeutically effective dose of the antibody or antigen-binding fragment is administered for 12 weeks.

16. The method of any of claims 13 to 15, further comprising administering to the patient a third therapeutically effective amount of the antibody or antigen-binding fragment.

17. 17. The method of claim 16, wherein the third therapeutically effective amount is 340 mg.

18. 17. The method of claim 16, wherein the third therapeutically effective amount is 680 mg.

19. 19. The method of claim 16 or 18, wherein the second therapeutically effective dose of the antibody or antigen-binding fragment is administered for 4 weeks, 12 weeks, or 28 weeks.

20. The method of any of claims 1 to 19, wherein the antibody, antigen-binding fragment, or pharmaceutical composition is administered in combination with at least one additional therapeutic measure.

21. 1. A method of treating CIDP, comprising administering to a patient in need of treatment thereof a first therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment is (a) a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence set forth in SEQ ID N·:27, an HCDR2 comprising the amino acid sequence set forth in SEQ ID N·:28, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID N·:29, and a light chain variable region comprising an LCDR1 comprising the amino acid sequence set forth in SEQ ID N·:30, an LCDR2 comprising the amino acid sequence set forth in SEQ ID N·:31, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID N·:32; or (b) a heavy chain variable region comprising an HCDR1 comprising the amino acid sequence set forth in SEQ ID N:49, an HCDR2 comprising the amino acid sequence set forth in SEQ ID N:22, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID N:23, and a light chain variable region comprising an LCDR1 comprising the amino acid sequence set forth in SEQ ID N:50, an LCDR2 comprising the amino acid sequence set forth in SEQ ID N:25, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID N:26; wherein the first therapeutically effective amount of the antibody or antigen-binding fragment is 680 mg administered subcutaneously once weekly, optionally for a period of about 12 weeks or more.

22. 22. The method of claim 21, further comprising administering to the patient a second therapeutically effective amount of the antibody or antigen-binding fragment, wherein the second therapeutically effective amount is 340 mg administered subcutaneously once weekly, optionally for about 12 weeks or more.

23. 23. The method of claim 22, further comprising administering to the patient a third therapeutically effective amount of the antibody or antigen-binding fragment, wherein the patient has relapsing CIDP and the third therapeutically effective amount is 680 mg administered subcutaneously once weekly, optionally for about 4 weeks or more, further optionally followed by administration of 340 mg subcutaneously once weekly for a period of time.

24. The method according to any one of claims 1 to 23, characterized in that the patient is a human being.

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