Methods of treating chronic inflammatory demyelinating polyneuropathy using anti-FCRN antibodies

Abstract

The present disclosure relates to methods of treating chronic inflammatory demyelinating polyneuropathy using anti-FcRn antibodies.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 374,644, filed on September 6, 2022, the entire disclosure of which is incorporated herein by reference.

[0003] Reference to Sequence Listing

[0004] The Sequence Listing XML related to this application is provided electronically in XML file format and is incorporated into this specification by reference. The XML file containing the Sequence Listing XML is named "MUNO - 011_01WO_ST26". The size of this XLM file is 66,055 bytes, created on August 18, 2023, and submitted electronically. Technical Field

[0005] The present disclosure relates to methods of treating chronic inflammatory demyelinating polyneuropathy using anti - FcRn antibodies. Background Art

[0006] In the United States, chronic inflammatory demyelinating polyneuropathy (CIDP) affects approximately 16,000 patients, and 70% of these patients require ongoing treatment. CIDP is characterized by demyelination of motor and sensory nerves. Although the cause of CIDP is not well understood, significant evidence suggests that the disease is immune - mediated (Mathey et al., Journal of Neurology, Neurosurgery & Psychiatry 2015; Wolbert et al., JCI Insight. February 13, 2020; 5(3):e132411. doi:10.1172 / jci.insight.132411). Multiple immune mechanisms, including cellular mechanisms (macrophages), humoral mechanisms, and the complement pathway, are involved in the pathogenesis of CIDP (Koike H et al., Neurol Ther. December 2020; 9(2):213 - 227; Querol et al., Neurotherapeutics. April 2022).

[0007] Autoantibodies have not been identified in 50 - 60% of CIDP patients, while anti - perineuronal myelin IgG has been found in 30 - 40% of patients (Mathey et al.). Multiple immune mechanisms, including cellular mechanisms (macrophages), humoral mechanisms, and the complement pathway, are involved in the pathogenesis of CIDP (Mathey et al., Koike et al.).

[0008] For many patients, CIDP is a long-term chronic disease that typically requires ongoing treatment. However, existing CIDP treatments can have side effects and pose logistical challenges. Accordingly, there remains an unmet need for effective treatments that can be conveniently administered.

[0009] Antibodies are immune proteins that bind to specific antigens. In most animals, including humans and mice, antibodies are composed of paired heavy and light chain polypeptide chains, each chain consisting of two distinct regions called the variable and constant regions. The variable regions of the heavy and light chains exhibit significant sequence diversity between antibodies and are responsible for binding to the target antigen. The constant regions exhibit low sequence diversity and are responsible for binding to a variety of native proteins to initiate various biochemical events.

[0010] Under normal conditions, the average serum half-life of most IgG (i.e., IgG1, IgG2, and IgG4, excluding the IgG3 isotype) in humans is approximately 21 days (Morell et al., J. Clin. Invest. 49(4): 673-80, 1970), a relatively long period compared to the serum half-lives of other plasma proteins. Relative to this extended serum half-life of IgG, IgG that enters cells via endocytosis can strongly bind to the neonatal Fc receptor (FcRn) in endosomes at a pH of 6.0 to avoid degradation via the lysosomal pathway (FcRn, an Fcγ (gamma) receptor, also known as FcRP, FcRB, or the Brambell receptor). When the IgG-FcRn complex cycles to the plasma membrane, IgG rapidly dissociates from FcRn in the bloodstream at a slightly alkaline pH (approximately 7.4). Through this receptor-mediated recycling mechanism, FcRn effectively rescues IgG from degradation in lysosomes, thereby extending the half-life of IgG (Roopenian et al., J. Immunol. 170: 3528, 2003).

[0011] FcRn is a non-covalent heterodimer that is typically present in the endosomes of endothelial and epithelial cells. FcRn 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 I molecule family, which molecules share β2m as a common light chain. The FcRn chain has a molecular weight of approximately 46 kDa and consists of an extracellular structure containing the α1, α2, and α3 heavy chain domains and the β2m light chain domain, and has a single sugar chain, a single transmembrane segment, and a relatively short cytoplasmic tail. SUMMARY OF THE INVENTION

[0012] The present invention provides a method for treating CIDP in a patient in need thereof, comprising administering to the patient a first therapeutically effective amount of an anti-FcRn antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment comprises: (a) a heavy-chain variable region comprising: an HCDR1 comprising the amino acid sequence shown in SEQ ID No: 27, an HCDR2 comprising the amino acid sequence shown in SEQ ID No: 28, and an HCDR3 comprising the amino acid sequence shown in SEQ ID No: 29; and a light-chain variable region comprising: an LCDR1 comprising the amino acid sequence shown in SEQ ID No: 30, an LCDR2 comprising the amino acid sequence of SEQ ID No: 31, and an LCDR3 comprising the amino acid sequence shown in SEQ ID No: 32; or (b) a heavy-chain variable region comprising: an HCDR1 comprising the amino acid sequence shown in SEQ ID No: 49, an HCDR2 comprising the amino acid sequence shown in SEQ ID No: 22, and an HCDR3 comprising the amino acid sequence shown in SEQ ID No: 23; and a light-chain variable region comprising: an LCDR1 comprising the amino acid sequence shown in SEQ ID No: 50, an LCDR2 comprising the amino acid sequence shown in SEQ ID No: 25, and an LCDR3 comprising the amino acid sequence shown in SEQ ID No: 26.

[0013] In some embodiments, the antibody or antigen-binding fragment comprises: (a) a heavy-chain variable region comprising an amino acid sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to the sequence shown in SEQ ID No: 6, and a light-chain variable region comprising an amino acid sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to the sequence shown in SEQ ID No: 16; or (b) a heavy-chain variable region comprising an amino acid sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to the sequence shown in SEQ ID No: 51, and a light-chain variable region comprising an amino acid sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to the sequence shown in SEQ ID No: 52. In some embodiments, the antibody or antigen-binding fragment comprises: (a) a heavy-chain variable region comprising the sequence shown in SEQ ID No: 6, and a light-chain variable region comprising the sequence shown in SEQ ID No: 16; or (b) a heavy-chain variable region comprising the sequence shown in SEQ ID No: 51, and a light-chain variable region comprising the sequence shown in SEQ ID No: 52.

[0014] In some embodiments, the antibody or antigen-binding fragment binds FcRn at pH 6.0 or pH 7.4 with a K D (dissociation constant) of from 0.01 nM to 2 nM. In some embodiments, KD Measured by surface plasmon resonance (SPR).

[0015] 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.

[0016] In some embodiments, the first therapeutically effective amount of the antibody or antigen-binding fragment is from 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 from 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 effective amount of the antibody or antigen-binding fragment is administered for 12 weeks. In some embodiments, the first 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 a week.

[0017] In some embodiments, the method further comprises administering to the subject a second therapeutically effective amount of the antibody or antigen-binding fragment. In some embodiments, the second therapeutically effective amount is 340 mg. In some embodiments, the second therapeutically effective amount of the antibody or antigen-binding fragment is administered for 12 weeks. In some embodiments, the first 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 a week.

[0018] In some embodiments, the method further comprises administering to the subject 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.

[0019] In some embodiments, patients who do not experience relapse during the administration of the second therapeutically effective amount are administered 340 mg of the antibody or antigen-binding fragment. In some embodiments, patients who experience relapse during the administration of the second therapeutically effective amount are administered 680 mg of the antibody or antigen-binding fragment (e.g., for at least 4 weeks), and then 340 mg of the antibody or antigen-binding fragment. In some embodiments, the antibody or antigen-binding fragment is administered subcutaneously once a week.

[0020] In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered in combination with at least one additional therapeutic agent.

[0021] In another aspect, the present disclosure provides a method of treating CIDP in a patient in need thereof, comprising administering to the patient a first therapeutically effective amount of an anti-FcRn antibody or an antigen-binding fragment thereof; wherein the antibody or antigen-binding fragment comprises: (a) a heavy chain variable region comprising: HCDR1 comprising the amino acid sequence shown in SEQ ID No: 27, HCDR2 comprising the amino acid sequence shown in SEQ ID No: 28, and HCDR3 comprising the amino acid sequence shown in SEQ ID No: 29; and a light chain variable region comprising: LCDR1 comprising the amino acid sequence shown in SEQ ID No: 30, LCDR2 comprising the amino acid sequence shown in SEQ ID No: 31, and LCDR3 comprising the amino acid sequence shown in SEQ ID No: 32; or (b) a heavy chain variable region comprising: HCDR1 comprising the amino acid sequence shown in SEQ ID No: 49, HCDR2 comprising the amino acid sequence shown in SEQ ID No: 22, and HCDR3 comprising the amino acid sequence shown in SEQ ID No: 23; and a light chain variable region comprising: LCDR1 comprising the amino acid sequence shown in SEQ ID No: 50, LCDR2 comprising the amino acid sequence shown in SEQ ID No: 25, and LCDR3 comprising the amino acid sequence shown in SEQ ID No: 26; and wherein the first therapeutically effective amount of the antibody or antigen-binding fragment is administered subcutaneously at 340 mg or 680 mg once a week, optionally wherein the administration continues for about 12 weeks or longer.

[0022] 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 a week, optionally wherein the administration continues for about 12 weeks or longer.

[0023] 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 relapsed with CIDP, wherein the third therapeutically effective amount is 680 mg, administered subcutaneously once a week, optionally wherein the administration continues for about 4 weeks or longer, and optionally subsequently 340 mg is administered subcutaneously once a week for a period of time.

[0024] In some embodiments, the patient is human. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1Schematic diagram showing a Phase 2B trial of an anti-FcRn antibody for the treatment of CIDP. Four groups (A - D) were defined according to CIDP treatment at screening. Participants in groups A, B, and D who did not deteriorate at Week 0 will withdraw from the study at Week 0. Participants who were non-responders in Phase 1 and completed Week 12 and the subsequent 4-week follow-up will withdraw from the study. Phase 1 non-responders who required protocol-prohibited rescue treatment before Week 12 will discontinue the IMP and may resume standard of care; these participants will be encouraged to continue to participate in the safety follow-up study during Week 12 and the follow-up period. Participants who relapsed in Phase 2 or did not relapse in Phase 2 and completed Phase 2 will be eligible to participate in the long-term extension study. Abbreviations: CIDP = chronic inflammatory demyelinating polyneuropathy; EAN / PNS = European Academy of Neurology / Peripheral Nerve Society; Ig = immunoglobulin (IVIg and SCIg) therapy; IMP = investigational medicinal product; LTE = long-term extension; PLEX = plasma exchange; QW = every week; Wk = weekly; SC = subcutaneous; INCAT = Inflammatory Neuropathy Cause and Treatment. Detailed Description

[0026] To facilitate a better understanding of the present disclosure, certain terms are defined throughout the detailed description. Unless otherwise defined herein, all scientific and technical terms used in connection with the present disclosure have the same meaning as commonly understood by one of ordinary skill in the art. For any purpose, all references cited herein are hereby incorporated by reference. If the cited references conflict with the present disclosure, the specification shall prevail.

[0027] As used herein, unless the context clearly indicates otherwise, the singular forms of words also include the plural forms; for example, the terms "a", "an", and "the" are understood to be singular or plural. By way of example, "an element" means one or more elements. The term "or" means "and / or" unless the particular context otherwise indicates. All ranges (including ranges expressed in the form "between value X and value Y") include the endpoints and all points therebetween, unless the specific context otherwise indicates.

[0028] In some embodiments, the present disclosure relates to a method of treating CIDP by administering to a patient in need thereof an anti-FcRn antibody or an antigen-binding fragment thereof, or by administering to a patient in need thereof a pharmaceutical composition comprising at least one pharmaceutically acceptable carrier and an anti-FcRn antibody or an antigen-binding fragment thereof. In some embodiments, the present disclosure relates to the use of an anti-FcRn antibody or an antigen-binding fragment thereof in a method of treating CIDP, the treatment being by administering to a patient in need thereof an anti-FcRn antibody or antigen-binding fragment, or by administering to a patient in need thereof a pharmaceutical composition comprising at least one pharmaceutically acceptable carrier and an anti-FcRn antibody or antigen-binding fragment. In some embodiments, the present disclosure relates to the use of an anti-FcRn antibody or an antigen-binding fragment thereof in the preparation of a medicament for treating CIDP. In some embodiments, the present disclosure relates to an anti-FcRn antibody or an antigen-binding fragment thereof for use in a method of treating CIDP. Also disclosed is a pharmaceutical composition comprising an anti-FcRn antibody or an antigen-binding fragment thereof and at least one pharmaceutically acceptable carrier, and which is useful for the treatment methods and uses described herein.

[0029] As used herein, the term "treatment" and its cognates refer to the amelioration of a disease, disorder or condition (e.g., CIDP) or at least one distinguishable symptom thereof (e.g., any one or more of the signs and symptoms described herein). The term "treatment" includes, but is not limited to, the complete treatment or complete amelioration of one or more symptoms of CIDP. In some embodiments, "treatment" refers to at least partial amelioration of at least one measurable physical parameter that may not be distinguishable in a patient, such as a decrease in at least one autoantibody and / or pathogenic antibody (e.g., pathogenic IgG) and / or total serum IgG levels. In some embodiments, "treatment" refers to inhibiting the progression of CIDP physically (e.g., stabilization of distinguishable symptoms), physiologically (e.g., stabilization of body parameters), or both. In some embodiments, "treatment" refers to slowing or reversing the progression of CIDP.

[0030] The antibodies, antigen-binding fragments and pharmaceutical compositions disclosed herein can also be used to prevent or prophylax CIDP. For example, a prophylactic method can include administering to a subject at risk of developing CIDP an antibody, antigen-binding fragment or pharmaceutical composition disclosed herein to prevent or reduce the likelihood of developing CIDP or at least one distinguishable symptom thereof.

[0031] The terms "subject" and "patient" are used interchangeably herein and refer to any human or non-human animal. Non-human animals include all vertebrates (e.g., mammals and non-mammals), such as any mammal. 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 having or suspected of having CIDP.

[0032] In some embodiments, a patient in need of treatment for CIDP exhibits one or more signs and symptoms of CIDP (e.g., symmetric weakness of proximal and distal muscles around the hips, shoulders, hands, and / or feet, impaired motor function, altered or lost sensation, incoordination, numbness, tingling or pins and needles, fatigue, burning sensation, pain, clumsiness, dysphagia, diplopia, atrophy, diminished or absent deep tendon reflexes, abnormal gait, and / or impaired response to various sensory stimuli) and / or has been diagnosed by a treating physician as having any form of the disease.

[0033] In some embodiments, a patient in need of treatment for CIDP (or a sample from the patient) has a detectable level of anti-myelin peripheral nerve IgG. In some embodiments, anti-myelin peripheral nerve IgG is present in the patient's blood. In some embodiments, the anti-myelin peripheral nerve IgG is anti-myelin peripheral nerve IgG1. In some embodiments, the anti-myelin peripheral nerve IgG is anti-myelin peripheral nerve IgG2. In some embodiments, the anti-myelin peripheral nerve IgG is anti-myelin peripheral nerve IgG3. In some embodiments, the anti-myelin peripheral nerve IgG is anti-myelin peripheral nerve IgG4.

[0034] In some embodiments, a patient in need of treatment (or a sample from the patient) has a detectable level of anti-paranodal IgG. In some embodiments, anti-paranodal IgG is present in the patient's blood. In some embodiments, the anti-paranodal IgG is anti-paranodal IgG1. In some embodiments, the anti-paranodal IgG is anti-paranodal IgG2. In some embodiments, the anti-paranodal IgG is anti-paranodal IgG3. In some embodiments, the anti-paranodal IgG is anti-paranodal IgG4. Paranodal antigen proteins include, for example, NF-155 and contactin-1.

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

[0036] Another embodiment is an anti-FcRn antibody or antigen-binding fragment thereof for use in a method of 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.

[0037] Another embodiment is the use of an anti-FcRn antibody or antigen-binding fragment thereof in a method of 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 composition comprising at least one pharmaceutically acceptable carrier and a therapeutically effective amount of the antibody or antigen-binding fragment.

[0038] Another embodiment is 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.

[0039] In various embodiments of the treatment methods, uses, and compositions disclosed herein, the anti-FcRn antibody or antigen-binding fragment functions as a non-competitive inhibitor of IgG in 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, such inhibition promotes clearance (i.e., removal) of at least one autoantibody and / or pathogenic antibody from the subject. 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 in a sample from the subject. In various embodiments, a reduction in the level of at least one autoantibody and / or pathogenic antibody results in and / or is associated with an improvement in at least one clinical parameter of CIDP.

[0040] As used herein, the term "autoantibody" refers to an antibody produced by an organism's immune system that targets one or more of the organism's own proteins, tissues, and / or organs. For example, one or more autoantibodies may be produced when a human patient's immune system fails to distinguish between "self" and "non-self". In some embodiments, the autoantibody is a pathogenic antibody (e.g., 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 contributes to the pathogenesis of one or more diseases, disorders, or conditions (e.g., CIDP) and / or causes one or more diseases, disorders, or conditions (e.g., CIDP).

[0041] In some embodiments, the pathogenic antibody is pathogenic IgG (e.g., pathogenic IgG1, IgG2, IgG3, or IgG4). In some embodiments, the pathogenic antibody and / or pathogenic IgG is anti-peripheral myelin IgG. In some embodiments, the pathogenic antibody is anti-paranodal IgG.

[0042] In some embodiments, a patient is treated with an antibody, antigen-binding fragment, or pharmaceutical composition described herein, e.g., using a method described herein, to reduce the level of anti-peripheral myelin IgG (e.g., anti-peripheral myelin IgG1, anti-peripheral myelin IgG2, anti-peripheral myelin IgG3, and / or anti-peripheral myelin 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., relative to the level of anti-peripheral myelin IgG prior to treatment. In some embodiments, a patient is treated with an antibody, antigen-binding fragment, or pharmaceutical composition described herein, e.g., using a method described herein, to reduce the level of anti-paranodal IgG (e.g., anti-paranodal IgG1, anti-paranodal IgG2, anti-paranodal IgG3, and / or anti-paranodal 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., relative to the level of anti-paranodal IgG prior to treatment.

[0043] 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-peripheral nerve IgG1). In some embodiments, the autoantibody and / or pathogenic antibody is IgG2 (e.g., pathogenic IgG2, e.g., anti-paranodal IgG2 or anti-peripheral nerve IgG2). In some embodiments, the autoantibody and / or pathogenic antibody is IgG3 (e.g., pathogenic IgG3, e.g., anti-paranodal IgG3 or anti-peripheral nerve IgG3). In some embodiments, the autoantibody and / or pathogenic antibody is IgG4 (e.g., pathogenic IgG4, e.g., anti-paranodal IgG4 or anti-peripheral nerve IgG4). In some embodiments, the autoantibody is a pathogenic antibody.

[0044] In various embodiments of the therapeutic methods, uses, and compositions disclosed herein, an 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 substantially no affinity for IgG at physiological pH rather than 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. Accordingly, in various embodiments, an anti-FcRn antibody or antigen-binding fragment that binds to FcRn non-competitively and specifically with IgG in a non-pH-dependent manner has an advantage over conventional competitive inhibitors (i.e., antibodies that bind to FcRn competitively with IgG) because it can provide a therapeutic or prophylactic effect even at significantly low concentrations through FcRn-mediated signaling of IgG. Further, in various embodiments, during the intracellular trafficking process in the state of being bound to FcRn, the anti-FcRn antibody or antigen-binding fragment can maintain its binding to FcRn with an affinity higher than that of IgG in the blood. Thus, in various embodiments, the anti-FcRn antibody or antigen-binding fragment can inhibit the binding of IgG to FcRn, even in endosomes where the acidic pH environment allows IgG to bind to FcRn, thereby promoting the clearance of IgG. In various embodiments, the anti-FcRn antibody or antigen-binding fragment is RVT-1401 (also referred to herein as HL161BKN and bartolimab). In some embodiments, the antibody or antigen-binding fragment is RVT-1401 or an antigen-binding fragment thereof. RVT-1401 / bartolimab is also described, for example, in International Patent Application Publication WO2015 / 167293 (referred to herein as HL161BKN), the entire content of which is incorporated herein by reference.

[0045] The CDR sequences of illustrative anti-FcRn antibodies are listed in Table 1.

[0046] Table 1: CDR Sequences of the Heavy and Light Chain Variable Domains of Selected Human FcRn Antibodies

[0047]

[0048]

[0049] In some embodiments, the antibody or antigen-binding fragment comprises the three heavy-chain CDR amino acid sequences of SEQ ID No:27 (HCDR1), SEQ ID No:28 (HCDR2), and SEQ ID No:29 (HCDR3); and the three light-chain CDR amino acid sequences of SEQ ID No:30 (LCDR1), SEQ ID No:31 (LCDR2), and SEQ ID No:32 (LCDR3). In some embodiments, the antibody or antigen-binding fragment comprises the three heavy-chain CDR amino acid sequences of SEQ ID No:49 (HCDR1), SEQ ID No:22 (HCDR2), and SEQ ID No:23 (HCDR3); and the three light-chain CDR amino acid sequences of SEQ ID No:50 (LCDR1), SEQ ID No:25 (LCDR2), and SEQ ID No:26 (LCDR3).

[0050] Table 2 lists exemplary heavy and light chain variable regions of anti-FcRn antibodies.

[0051] Table 2: Amino acid sequences of the heavy and light chain variable domains of selected human FcRn antibodies

[0052]

[0053]

[0054] In some embodiments, the antibody or antigen-binding fragment comprises: a heavy-chain variable region comprising an amino acid sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to the sequence shown in SEQ ID No:6, and a light-chain variable region comprising an amino acid sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to the sequence shown in SEQ ID No:16. In some embodiments, the antibody or antigen-binding fragment comprises: heavy-chain amino acids comprising an amino acid sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to the sequence shown in SEQ ID No:46; and light-chain amino acids comprising an amino acid sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to the sequence shown in SEQ ID No:48. In some embodiments, the antibody or antigen-binding fragment comprises: heavy-chain amino acids comprising an amino acid sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to the sequence shown in SEQ ID No:51; and light-chain amino acids comprising an amino acid sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to the sequence shown in SEQ ID No:52.

[0055] In some embodiments, the antibody or antigen-binding fragment comprises: the amino acid sequence of the heavy chain variable region of SEQ ID No: 6; and the amino acid sequence of the light chain variable region of SEQ ID No: 16. In some embodiments, the antibody or antigen-binding fragment comprises: the amino acid sequence of the heavy chain of SEQ ID No: 46; and the amino acid sequence of the light chain of SEQ ID No: 48. In some embodiments, the antibody or antigen-binding fragment comprises: the amino acid sequence of the heavy chain of SEQ ID No: 51; and the amino acid sequence of the light chain of SEQ ID No: 52.

[0056] Table 3 lists illustrative heavy and light chains of anti-FcRn antibodies.

[0057] Table 3: Amino acid sequences of full-length heavy and light chains of selected human FcRn antibodies

[0058]

[0059]

[0060] In some embodiments, the antibody or antigen-binding fragment comprises: a heavy chain comprising an amino acid sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to the sequence shown in SEQ ID No: 46, 53 or 55, and a light chain comprising an amino acid sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to the sequence shown in SEQ ID No: 48, 54 or 56. In some embodiments, the antibody or antigen-binding fragment comprises: a heavy chain comprising the sequence shown in SEQ ID No: 46, 53 or 55; and a light chain comprising the sequence shown in SEQ ID No: 48, 54 or 56.

[0061] "Affinity" of binding 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.

[0062] As used herein, the terms "specificity", "specifically bind" and "bind specifically" refer to the binding reaction between an antibody or antigen-binding fragment thereof (e.g., an anti-FcRn antibody or antigen-binding fragment thereof) and a target antigen (e.g., FcRn) in a heterogeneous population of proteins and other biologics. The binding specificity of an antibody can be tested by comparing binding to an appropriate antigen with binding to an alternative antigen or antigen mixture under a given set of conditions. An antibody is considered specific if it binds to an appropriate antigen with an affinity that is at least 2-fold, at least 5-fold, or at least 10-fold (or more) higher than that of an alternative antigen or antigen mixture.

[0063] A "specific antibody" or "target-specific antibody" is an antibody that binds only to a target antigen (e.g., FcRn) but does not bind (or exhibits 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 specificity of less than 1×10 -6 M, less than 1×10 -7 M, less than 1×10 -8 M, less than 1×10 -9 M, less than 1×10 -10 M, less than 1×10 -11 M, less than 1×10 -12 M or less than 1×10 -13 M of K D In some embodiments, at pH 6.0 or pH 7.4, KD is about 0.01 nM to about 2 nM. In some embodiments, at pH 7.4, K D In some embodiments, the KD is about 2 nM or less to 900 pM or less at pH 6.0.

[0064] As used herein, the term "K D ” refers to the equilibrium dissociation constant of antibody-antigen binding, which is composed of k d With k a The ratio (i.e. k d / k a ) is obtained, usually expressed as a molar concentration (M). assoc " or "k a ” refers to the binding rate of a specific antibody-antigen interaction, while the term “k dis " or "k d ” refers to the dissociation rate of a specific antibody-antigen interaction. d and / or k aMeasurements can be performed at 25°C or 37°C. The K D values of antibodies and antigen-binding fragments can be determined using methods established in the art (see, for example, Pollard, Mol. Biol. Cell 21(23):4061-7, 2010). In some embodiments, the K D is measured by direct binding and / or competitive binding assays (e.g., surface plasmon resonance and / or competitive ELISA). In some embodiments, the K D is measured by surface plasmon resonance (e.g., human FcRn immobilized surface plasmon resonance). In some embodiments, the K D of the anti-FcRn antibodies or antigen-binding fragments disclosed herein is measured by human FcRn immobilized surface plasmon resonance.

[0065] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, the anti-FcRn antibodies or antigen-binding fragments have a K D (dissociation constant) of about 0.01 nM to 2 nM at pH 6.0 and pH 7.4, as determined by, for example, surface plasmon resonance. In some embodiments, the anti-FcRn antibodies or antigen-binding fragments have a K D of about 300 pM or less to about 2 nM or less at pH 7.4, and / or a K D of about 2 nM or less to about 900 pM or less at pH 6.0, as determined by, for example, surface plasmon resonance. In some embodiments, the anti-FcRn antibodies or antigen-binding fragments bind to the exterior of the cell and maintain their binding to endosomes when bound. In some embodiments, the anti-FcRn antibodies or antigen-binding fragments effectively block the binding of one or more autoantibodies to FcRn (e.g., human FcRn), as determined by, for example, a blocking assay performed using cells expressing human FcRn and FACS.

[0066] As used herein, the term "anti-FcRn antibody" or "antibody that specifically binds FcRn" refers to any form of antibody or its antigen-binding fragment that specifically binds FcRn, e.g., an antibody or its antigen-binding fragment that binds with a K D of less than 2 nM at pH 6.0 or pH 7.4, as determined by, for example, surface plasmon resonance (e.g., human FcRn immobilized surface plasmon resonance). The term includes monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, and biological functional fragments, provided that they specifically bind FcRn.

[0067] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, the anti-FcRn antibodies or antigen-binding fragments comprise:

[0068] ● CDR1, which comprises an amino acid sequence having at least 90% identity with one or more amino acid sequences selected from the group consisting of SEQ ID No: 21, 24, 27, 30, 33, 36, 39, 42, 49 and 50;

[0069] ● CDR2, which comprises an amino acid sequence having at least 90% identity with one or more amino acid sequences selected from the group consisting of SEQ ID No: 22, 25, 28, 31, 34, 37, 40 and 43; and

[0070] ● CDR3, which comprises an amino acid sequence having at least 90% identity with one or more amino acid sequences selected from the group consisting of SEQ ID No: 23, 26, 29, 32, 35, 38, 41 and 44.

[0071] In some embodiments of the therapeutic methods, uses and compositions disclosed herein, the anti-FcRn antibody or antigen-binding fragment comprises:

[0072] ● CDR1, which comprises an amino acid sequence having 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% identity with one or more amino acid sequences selected from the group consisting of SEQ ID No: 21, 24, 27, 30, 33, 36, 39, 42, 49 and 50;

[0073] ● CDR2, which comprises an amino acid sequence having 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% identity with one or more amino acid sequences selected from the group consisting of SEQ ID No: 22, 25, 28, 31, 34, 37, 40 and 43; and

[0074] ● CDR3, which comprises an amino acid sequence having 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% identity with one or more amino acid sequences selected from the group consisting of SEQ ID No: 23, 26, 29, 32, 35, 38, 41 and 44.

[0075] 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.

[0076] 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 that is the same as or homologous to the amino acid sequences described herein. The terms "identity" or "homology" refer to the relationship between the sequences of two or more polypeptides, 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 strings of two or more 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 gaps and the length of each gap that need to be introduced for optimal alignment of the two sequences. Comparison of sequences and determination of the percent identity between two sequences can be accomplished using a mathematical algorithm. For sequence comparison, typically one sequence is used as a reference sequence to be compared with a test sequence. When using a sequence comparison algorithm, the test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Default program parameters can be used, or alternative parameters can be specified. Then, the sequence comparison algorithm 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 also be used as a "query sequence" to perform a search of public databases, e.g., to identify related sequences. For example, such a search can be performed using the BLAST program of Altschul et al. (J. Mol. Biol. 215:403-10, 1990).

[0077] In the case of comparison and alignment to obtain maximum correspondence within a comparison window or specified region, two sequences are "substantially identical" if they have the same specified percentage of amino acid residues (i.e., 60% identity within the specified region, or within the entire sequence if no region is specified, optionally 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99% identity), as measured using one of the following sequence comparison algorithms or by manual alignment and visual inspection. Optionally, the identity exists in a region of at least about 10 amino acids, or a region of about 20, 50, 200 or more amino acids. In some embodiments, the anti-FcRn antibodies and antigen-binding fragments described herein comprise at least one amino acid sequence that has at least 90% identity to a sequence selected from the group consisting of SEQ ID No: 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 has 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% identity to a sequence selected from the group consisting of SEQ ID No: 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 - 48.

[0078] In some embodiments, the antibody or antigen-binding fragment comprises: a heavy chain variable region that comprises:

[0079] ● CDR1 comprising the amino acid sequence of SEQ ID No: 21, CDR2 comprising the amino acid sequence of SEQ ID No: 22, and CDR3 comprising the amino acid sequence of SEQ ID No: 23;

[0080] ● CDR1 comprising the amino acid sequence of SEQ ID No: 27, CDR2 comprising the amino acid sequence of SEQ ID No: 28, and CDR3 comprising the amino acid sequence of SEQ ID No: 29;

[0081] ● CDR1 comprising the amino acid sequence of SEQ ID No: 33, CDR2 comprising the amino acid sequence of SEQ ID No: 34, and CDR3 comprising the amino acid sequence of SEQ ID No: 35;

[0082] ● CDR1 comprising the amino acid sequence of SEQ ID No: 39, CDR2 comprising the amino acid sequence of SEQ ID No: 40, and CDR3 comprising the amino acid sequence of SEQ ID No: 41; or

[0083] ● A CDR1 comprising the amino acid sequence of SEQ ID No:49, a CDR2 comprising the amino acid sequence of SEQ ID No:22, and a CDR3 comprising the amino acid sequence of SEQ ID No:23.

[0084] In some embodiments, the antibody or antigen-binding fragment comprises a light chain variable region that includes:

[0085] ● A CDR1 comprising the amino acid sequence of SEQ ID No:24, a CDR2 comprising the amino acid sequence of SEQ ID No:25, and a CDR3 comprising the amino acid sequence of SEQ ID No:26;

[0086] ● A CDR1 comprising the amino acid sequence of SEQ ID No:30, a CDR2 comprising the amino acid sequence of SEQ ID No:31, and a CDR3 comprising the amino acid sequence of SEQ ID No:32;

[0087] ● A CDR1 comprising the amino acid sequence of SEQ ID No:36, a CDR2 comprising the amino acid sequence of SEQ ID No:37, and a CDR3 comprising the amino acid sequence of SEQ ID No:38;

[0088] ● A CDR1 comprising the amino acid sequence of SEQ ID No:42, a CDR2 comprising the amino acid sequence of SEQ ID No:43, and a CDR3 comprising the amino acid sequence of SEQ ID No:44; or

[0089] ● A CDR1 comprising the amino acid sequence of SEQ ID No:50, a CDR2 comprising the amino acid sequence of SEQ ID No:25, and a CDR3 comprising the amino acid sequence of SEQ ID No:26.

[0090] 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:

[0091] ● A heavy chain variable region that includes: a CDR1 (HCDR1) comprising the amino acid sequence of SEQ ID No:21, a CDR2 (HCDR2) comprising the amino acid sequence of SEQ ID No:22, and a CDR3 (HCDR3) comprising the amino acid sequence of SEQ ID No:23; and a light chain variable region that includes: a CDR1 (LCDR1) comprising the amino acid sequence of SEQ ID No:24, a CDR2

[0092] (LCDR2) and CDR3 (LCDR3) comprising the amino acid sequence of SEQ ID No:26;

[0093] ● A heavy chain variable region comprising: CDR1 (HCDR1) comprising the amino acid sequence of SEQ ID No:27, CDR2 (HCDR2) comprising the amino acid sequence of SEQ ID No:28, and CDR3 (HCDR3) comprising the amino acid sequence of SEQ ID No:29; and a light chain variable region comprising: CDR1 (LCDR1) comprising the amino acid sequence of SEQ ID No:30, CDR2

[0094] (LCDR2) and CDR3 (LCDR3) comprising the amino acid sequence of SEQ ID No:32;

[0095] ● A heavy chain variable region comprising: CDR1 (HCDR1) comprising the amino acid sequence of SEQ ID No:33, CDR2 (HCDR2) comprising the amino acid sequence of SEQ ID No:34, and CDR3 (HCDR3) comprising the amino acid sequence of SEQ ID No:35; and a light chain variable region comprising: CDR1 (LCDR1) comprising the amino acid sequence of SEQ ID No:36, CDR2

[0096] (LCDR2) and CDR3 (LCDR3) comprising the amino acid sequence of SEQ ID No:38;

[0097] ● A heavy chain variable region comprising: CDR1 (HCDR1) comprising the amino acid sequence of SEQ ID No:39, CDR2 (HCDR2) comprising the amino acid sequence of SEQ ID No:40, and CDR3 (HCDR3) comprising the amino acid sequence of SEQ ID No:41; and a light chain variable region comprising: CDR1 (LCDR1) comprising the amino acid sequence of SEQ ID No:42, CDR2

[0098] (LCDR2) and CDR3 (LCDR3) comprising the amino acid sequence of SEQ ID No:44; and

[0099] ● Heavy chain variable region, which comprises: CDR1 (HCDR1) comprising the amino acid sequence of SEQ ID No: 49, CDR2 (HCDR2) comprising the amino acid sequence of SEQ ID No: 22, and CDR3 (HCDR3) comprising the amino acid sequence of SEQ ID No: 23; and light chain variable region, which comprises: CDR1 (LCDR1) comprising the amino acid sequence of SEQ ID No: 50, CDR2

[0100] (LCDR2) comprising the amino acid sequence of SEQ ID No: 25, and CDR3 (LCDR3) comprising the amino acid sequence of SEQ ID No: 26.

[0101] 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, which comprise one or more amino acid sequences selected from the group consisting of the amino acid sequences of SEQ ID No: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 51, and 52.

[0102] In some embodiments, the antibody or antigen-binding fragment comprises: a heavy chain variable region comprising the amino acid sequence of SEQ ID No: 2, 4, 6, 8, 10, or 51 and / or a light chain variable region comprising the amino acid sequence of SEQ ID No: 12, 14, 16, 18, 20, or 52.

[0103] 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:

[0104] ● A heavy chain variable region comprising the amino acid sequence of SEQ ID No: 2 and a light chain variable region comprising the amino acid sequence of SEQ ID No: 12;

[0105] ● A heavy chain variable region comprising the amino acid sequence of SEQ ID No: 4 and a light chain variable region comprising the amino acid sequence of SEQ ID No: 14;

[0106] ● A heavy chain variable region comprising the amino acid sequence of SEQ ID No: 6 and a light chain variable region comprising the amino acid sequence of SEQ ID No: 16;

[0107] ● A heavy chain variable region comprising the amino acid sequence of SEQ ID No: 8 and a light chain variable region comprising the amino acid sequence of SEQ ID No: 18;

[0108] ● A heavy chain variable region comprising the amino acid sequence of SEQ ID No: 10 and a light chain variable region comprising the amino acid sequence of SEQ ID No: 20; and

[0109] ● A heavy chain variable region comprising the amino acid sequence of SEQ ID No:51 and a light chain variable region comprising the amino acid sequence of SEQ ID No:52.

[0110] As used herein, the terms "fragment", "antibody fragment", and "antigen-binding fragment" when used in reference to an antibody 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-competitively interfering with the binding of IgG to FcRn). Antigen-binding fragments can also be present in larger macromolecules, such as bispecific, trispecific, and multispecific antibodies, such as diabodies, triabodies, and tetra-bodies. Examples of antigen-binding fragments include, but are not limited to, single-chain antibodies, Fab fragments, F(ab′)2 fragments, Fd, scFv, domain antibodies, bispecific antibodies, microantibodies, sterol regulatory binding protein cleavage activating protein (scap), chelate recombinant antibodies, triabodies or diabodies, intrabodies, nanobodies, and small modular immunopharmaceuticals (SMIP).

[0111] In some embodiments, the antibody or antigen-binding fragment is a binding domain immunoglobulin fusion protein, a camelized antibody, an antibody containing VHH, an IgD antibody, an IgE antibody, an IgM antibody, an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody. In some embodiments, the antibody or antigen-binding fragment comprises: a derivative in the antibody constant region. In some embodiments, the antibody or antigen-binding fragment is a synthetic antibody based on a protein scaffold having the ability to bind to FcRn.

[0112] In some embodiments, the antigen-binding fragment exhibits the same or similar properties as the full-length antibody. Without limitation, the antigen-binding fragment can be produced by any suitable method known in the art. For example, the various antigen-binding fragments described herein can be produced by enzymatic or chemical modification of a full-length antibody, de novo synthesis using recombinant DNA methods (e.g., scFv), or identification using a phage display library (see, e.g., Pini and Bracci, Curr. Protein Pept. Sci. 1(2):155-69, 2000). The utility of the antigen-binding fragment (e.g., specificity, binding affinity, activity) can be screened in the same manner as that of the full-length antibody.

[0113] In addition, antibodies or antigen-binding fragments having mutations in the variable region and / or constant region can be used in the therapeutic methods, uses, and compositions described herein. Examples of such antibodies or antigen-binding fragments include antibodies having conservative substitutions of amino acid residues in the variable region and / or constant region. As used herein, the term "conservative substitution" refers to a substitution with another amino acid residue having similar properties to the original amino acid residue. For example, lysine, arginine, and histidine have similar properties because they have basic side chains; aspartic acid and glutamic acid have similar properties because they have acidic side chains. In addition, glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, and tryptophan have similar properties because they have uncharged polar side chains; while alanine, valine, leucine, threonine, isoleucine, proline, phenylalanine, and methionine have similar properties because they have nonpolar side chains. In addition, tyrosine, phenylalanine, tryptophan, and histidine have similar properties because they have aromatic side chains. Thus, it will be apparent to those skilled in the art that even when an amino acid residue in a group showing similar properties as described above is substituted, the properties of the antibody or antigen-binding fragment may not change significantly.

[0114] In addition, in some embodiments, the antibody or antigen-binding fragment can be conjugated to another substance (e.g., a therapeutic agent or a detectable label). Substances that can be conjugated 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., any one or more of the standard therapeutic agents described herein and / or incorporated herein by reference); substances capable of inhibiting the activity of FcRn; and moieties that can physically bind to the antibody or antigen-binding fragment, e.g., to increase its stability and / or retention in circulation, e.g., in blood, serum, lymph, or other tissues. For example, the antibody or antigen-binding fragment can be conjugated to a polymer, e.g., a non-antigenic polymer such as a polyalkylene oxide or a polyethylene oxide. Suitable polymers will vary significantly by weight. Polymers having a number average molecular weight in the range of about 200 to about 35,000 (or about 1000 to about 15,000 and 2000 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 polyethylene polymer such as polyvinyl alcohol and polyvinylpyrrolidone. Non-limiting examples of such polymers include, but are not limited to: polyalkylene oxide homopolymers (such as polyethylene glycol (PEG) or polypropylene glycol), polyoxyethylated polyols, copolymers thereof, and block copolymers thereof, provided that the water solubility of the block copolymer is maintained.

[0115] In various embodiments, the antibody or antigen-binding fragment has a K of 0.01 nM to 2 nM at pH 6.0 or pH 7.4 D(Dissociation constant) Binding to FcRn, as measured by, for example, surface plasmon resonance.

[0116] 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 No:27), HCDR2 (SEQ ID No:28), HCDR3 (SEQ ID No:29)); and the three light-chain CDR amino acid sequences of RVT-1401 (LCDR1 (SEQ ID No:30), LCDR2 (SEQ ID No:31), LCDR3 (SEQ ID No:32)). In some embodiments, the antibody or antigen-binding fragment comprises: the heavy-chain variable region amino acid sequence of RVT-1401 (SEQ ID No:6); and the light-chain variable region amino acid sequence of RVT-1401 (SEQ ID No:16). In some embodiments, the antibody or antigen-binding fragment comprises: the heavy-chain amino acid sequence of RVT-1401 (SEQ ID No:46); and the light-chain amino acid sequence of RVT-1401 (SEQ ID No:48).

[0117] 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 agent. In various embodiments, the at least one additional therapeutic agent may comprise or consist of a standard-of-care therapeutic agent or treatment for CIDP.

[0118] As used herein, "combined" administration or "co - administration" refers to the delivery of two or more different treatments to a subject during the subject's CIDP. For example, in some embodiments, two or more treatments are delivered after the subject has been diagnosed with the disease and before the disease has been cured or eliminated, or when the subject is identified as being at risk but before the subject has developed symptoms of the disease. In some embodiments, when the delivery of the second treatment begins, the delivery of one treatment is still occurring, so there is an overlap. In some embodiments, the first treatment and the second treatment start simultaneously. These types of delivery are sometimes referred to herein as "simultaneous", "concurrent", or "concomitant" delivery. In other embodiments, the delivery of one treatment ends before the delivery of the second treatment begins. This type of delivery is sometimes referred to herein as "successive" or "sequential" delivery. In some embodiments, an antibody or antigen - binding fragment and at least one additional therapeutic agent are co - administered. In some embodiments, an antibody or antigen - binding fragment and at least one additional therapeutic agent are administered sequentially.

[0119] In some embodiments, the two treatments (e.g., an anti - FcRn antibody or antigen - binding fragment and a second therapeutic agent) are present in the same composition. This composition can be administered in any suitable form and by any suitable route. In other embodiments, the two treatments (e.g., an anti - FcRn antibody or antigen - binding fragment and a second therapeutic agent) are administered as separate compositions in any suitable form and by any suitable route. For example, a composition comprising an anti - FcRn antibody or antigen - binding fragment and a composition comprising a second therapeutic agent (e.g., a standard treatment for CIDP) can be administered simultaneously or sequentially in any order at different time points; in either case, they should be administered close enough in time to provide the desired therapeutic or prophylactic effect.

[0120] As used herein, the term "agent" refers to a compound, a mixture of compounds, a biological macromolecule, or an extract made from a biological material. The term "therapeutic agent" or "drug" refers to an agent that can modulate biological processes and / or has biological activity. The anti - FcRn antibodies and antigen - binding fragments described herein are examples of therapeutic agents.

[0121] As used herein, the term "standard therapeutic agent" refers to any therapeutic agent or other form of therapy that is accepted as an appropriate treatment for a particular type of disease (e.g., warm autoimmune hemolytic anemia). As used herein, the term "standard dose" or "standard administration regimen" refers to any customary or conventional administration regimen of a therapeutic agent, such as that proposed by the manufacturer, approved by a regulatory agency, or otherwise tested in human subjects to meet the needs of the average patient.

[0122] Examples of standard treatments and agents for CIDP include glucocorticoids (steroids), intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin (SCIg), and plasma exchange (PLEx).

[0123] The anti-FcRn antibodies and antigen-binding fragments described herein can be administered in combination with any of the exemplary standard therapeutic agents or therapies described herein. In some embodiments, the anti-FcRn antibodies and antigen-binding fragments described herein are administered in combination with glucocorticoids (steroids) or in combination with 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 therapeutic agents or therapies described herein. In some embodiments, the anti-FcRn antibodies and antigen-binding fragments described herein are administered alone or not in combination with any other agent or therapy.

[0124] The present invention also provides a pharmaceutical composition comprising an anti-FcRn antibody or an antigen-binding fragment thereof formulated together with at least one pharmaceutically acceptable carrier. The composition may also contain one or more additional therapeutic agents suitable for treating, for example, CIDP. Methods of formulating pharmaceutical compositions and suitable formulations are known in the art (e.g., see Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, PA). Suitable formulations may depend on the route of administration.

[0125] As used herein, "pharmaceutical composition" refers to a formulation of an anti-FcRn antibody or an antigen-binding fragment thereof, as well as other components suitable for administration to a patient, such as a pharmaceutically acceptable carrier and / or excipient. The pharmaceutical compositions provided herein are suitable for in vitro and / or in vivo administration. In some embodiments, the pharmaceutical compositions provided herein are in a form that permits administration and subsequent delivery of the desired biological activity of the active ingredient and / or achievement of a therapeutic effect. The pharmaceutical compositions provided herein preferably do not contain additional components that have unacceptable toxicity to the subject to whom the formulation is administered.

[0126] As used herein, the terms “pharmaceutically acceptable carrier” and “physiologically acceptable carrier” are used interchangeably and refer to a carrier, diluent, or excipient that does not cause significant irritation to a subject and does not abrogate the biological activity and properties of the administered antibody or antigen-binding fragment. Thus, a pharmaceutically acceptable carrier should be compatible with the active ingredient, such as an antibody or an antigen-binding fragment thereof, and can include saline, sterile water, Ringer's solution, buffered saline, glucose solution, maltodextrin solution, glycerol, ethanol, or a mixture of two or more thereof. A pharmaceutically acceptable carrier can also enhance or stabilize the composition, or can be used to facilitate the preparation of the composition. A pharmaceutically acceptable carrier can include other conventional additives, such as physiologically compatible additives including antioxidants, buffers, solvents, bacteriostatic agents, dispersion media, coatings, antibacterial and antifungal agents, isotonic agents, and absorption delaying agents. The carrier can be selected to minimize adverse side effects to 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.

[0127] As used herein, the term “excipient” refers to an inert substance added to a pharmaceutical composition to further facilitate the administration of the active ingredient. For example, formulations for parenteral administration can contain excipients such as sterile water or saline, polyalkylene glycols such as polyethylene glycol, vegetable oils, or hydrogenated naphthalene. Other excipients include, but are not limited to, calcium bicarbonate, calcium phosphate, various sugars, and various types of starches, cellulose derivatives, gelatin, ethylene-vinyl acetate copolymer particles, and surfactants including, for example, polysorbate 20.

[0128] In various embodiments of the therapeutic methods, uses, and compositions disclosed herein, anti-FcRn antibodies, antigen-binding fragments, or pharmaceutical compositions can be administered by a variety of methods known in the art. The route and / or mode of administration can vary depending on the desired outcome. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered by oral, intravenous, intramuscular, intraarterial, intramedullary, intradural, intracardiac, percutaneous, subcutaneous, intraperitoneal, enteral, sublingual, or topical routes. 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, e.g., intravenously or subcutaneously (e.g., by injection or infusion). In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered subcutaneously (e.g., by injection or infusion). In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered as one or more subcutaneous injections. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered as a single (i.e., one) subcutaneous injection. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered as 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 one or more subcutaneous injections. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is delivered by syringe, catheter, pumping system, or stent. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is delivered by syringe (e.g., prefilled syringe). Depending on the route of administration, the active compound, i.e., the anti-FcRn antibody or antigen-binding fragment, can be coated in a material to protect the compound from acids and other natural conditions that may inactivate the compound.

[0129] The antibody, antigen-binding fragment, or pharmaceutical composition can be formulated into various forms, such as powders, tablets, capsules, liquids, injections, ointments, or syrups, and / or contained in single-dose or multi-dose containers, such as sealed ampoules, vials, or syringes. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated into an injectable form. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated into an aqueous solution, suspension, or emulsion, with one or more excipients, diluents, dispersants, surfactants, binders, and / or lubricants. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is contained in a syringe (e.g., prefilled 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., a needle greater than about 25 gauge, greater than about 26 gauge, greater than about 27 gauge, greater than about 28 gauge, greater than about 29 gauge, and / or greater than about 30 gauge).

[0130] In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is formulated to achieve stability and / or prevent or minimize physical and / or chemical degradation prior to administration. Physical instability may involve processes such as denaturation and aggregation, while common chemical degradation pathways include, but are not limited to, cross-linking, deamidation, isomerization, oxidation, and cleavage (see, e.g., Wang et al., J. Pharm. Sci. 91(1):1-26, 2007). As used herein, the term “stable” or “stability,” when used to describe an antibody or its antigen-binding fragment, refers to the antibody or antigen-binding fragment remaining intact in a manner that maintains activity (e.g., binding to FcRn) and / or achieves 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) such that it is stable under standard storage conditions. 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) such that it is stable at high concentrations. In some embodiments, an antibody or antigen-binding fragment can be stably concentrated in a formulation up to about 150 mg / mL or higher. In some embodiments, an antibody or antigen-binding fragment can be stably concentrated in a formulation up to about 170 mg / mL or higher. In some embodiments, an antibody or antigen-binding fragment can be stably concentrated in a formulation to above about 170 mg / mL (e.g., about 180 mg / mL, about 200 mg / mL, about 220 mg / mL or higher). In some embodiments, a stably concentrated formulation (e.g., a formulation containing up to about 170 mg / mL or higher of an antibody or antigen-binding fragment) maintains an acceptable viscosity for administration via a small gauge needle. In some embodiments, the small gauge needle is greater than about 25 gauge, greater than about 26 gauge, greater than about 27 gauge, greater than about 28 gauge, greater than about 29 gauge, or greater than about 30 gauge.

[0131] The dosage regimen of an anti-FcRn antibody or antigen-binding fragment, whether administered alone or in combination with one or more additional therapeutic agents or therapies, can be adjusted to provide an optimal desired response (e.g., a therapeutic response). For example, a single bolus of an anti-FcRn antibody or antigen-binding fragment can be administered as a single dose, several separate doses can be administered over a predetermined period of time, or the dose of an anti-FcRn antibody or antigen-binding fragment can be proportionally decreased or increased as indicated by the exigencies of the treatment situation. For any particular subject, the specific dosage regimen can be adjusted over time according to the individual's needs and the professional judgment of the treating clinician. For example, in some embodiments, the dose of an anti-FcRn antibody or antigen-binding fragment can be appropriately determined by considering the severity, condition, age, medical history, etc. of the patient.

[0132] An anti-FcRn antibody or antigen-binding fragment can be formulated into a pharmaceutically acceptable dosage form by conventional methods known to those skilled in the art. For example, a parenteral composition can be formulated into unit dosage forms for ease of administration and uniformity of dosage. As used herein, "unit dosage form" refers to a physically discrete unit suitable as a single dose for a subject to be treated; each unit contains a predetermined quantity of the active compound calculated to produce the desired therapeutic effect, together with a pharmaceutically acceptable carrier. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated in unit dosage form. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated in unit dosage form for subcutaneous administration. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is formulated in unit dosage form for administration as one or more subcutaneous injections (e.g., a single 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 unit dosage form (e.g., as one or more subcutaneous injections) for self-administration by the patient and / or for administration by a treating clinician.

[0133] The dosage value of an anti-FcRn antibody or antigen-binding fragment, a composition comprising an anti-FcRn antibody or antigen-binding fragment, and / or any additional therapeutic agent can be selected based on the unique properties of the active compound and the specific therapeutic effect to be achieved. A physician or veterinarian can start the dosage of 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 can also start the dosage of 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. Generally, the effective dosage of an antibody or antigen-binding fragment for treating CIDP can vary depending on many different factors, such as the stage of the disease, the severity of the symptoms, and the prognosis of the subject. The dosage level selected can also depend on a variety of pharmacokinetic factors, including the activity of the specific composition or its ester, salt, or amide used, the route of administration, the time of administration, the excretion rate of the specific compound used, the duration of treatment, other drugs, compounds, and / or materials used in combination with the specific composition, factors such as the age, sex, weight, condition, general health, and medical history of the patient being treated, etc. In some embodiments, the treatment can be administered one or more times. Given the condition of a particular patient, intermittent and / or long-term (continuous) dosing strategies can be applied.

[0134] In some embodiments, a therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment is employed in the methods, uses, and pharmaceutical compositions of the present disclosure.

[0135] As used herein, the terms "therapeutically effective amount" and "therapeutically effective dose" are used interchangeably herein and refer to an amount sufficient to reduce at least one symptom or measurable parameter associated with a disease, disorder or condition such that the body function in a disease, disorder or condition resulting in impairment of a particular body function is normalized, and / or to provide an improvement in one or more clinical measurement parameters of the disease, disorder or condition or to slow the progression of the disease, disorder or condition. A therapeutically effective amount can, for example, be an amount sufficient to treat one or more symptoms of CIDP, reduce the severity of one or more symptoms of CIDP, delay the onset of one or more symptoms of CIDP and / or reduce the risk of occurrence of one or more symptoms of CIDP. A therapeutically effective amount and a therapeutically effective frequency of administration can be determined by methods known in the art and are discussed 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 agent. 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 agents are used in combination. In some embodiments, a therapeutically effective amount of the anti-FcRn antibody or antigen-binding fragment is an amount required to reduce the total serum IgG level and / or the level of at least one autoantibody (e.g., at least one IgG) in a patient having or suspected of having CIDP.

[0136] In some embodiments, a therapeutically effective amount of the anti-FcRn antibody or antigen-binding fragment is an 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 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% relative to the level prior to treatment with the anti-FcRn antibody or antigen-binding fragment. In some embodiments, a therapeutically effective amount of the anti-FcRn antibody or antigen-binding fragment is an 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% relative to the level prior to treatment with the anti-FcRn antibody or antigen-binding fragment. In some embodiments, a therapeutically effective amount of the anti-FcRn antibody or antigen-binding fragment is an 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 value. In some embodiments, the autoantibody is anti-peripheral nerve myelin IgG. In some embodiments, the autoantibody is anti-paranodal IgG.

[0137] As used herein, the phrase "total IgG level" or "total serum IgG level" refers to the serum endogenous IgG concentration in, for example, a patient or a biological sample from a patient (e.g., a blood sample).

[0138] As used herein, the phrase "level of at least one autoantibody" refers to the serum endogenous concentration of at least one autoantibody, e.g., in a patient or a biological sample from a patient.

[0139] As used herein, the phrase "level of at least one IgG" refers to the serum endogenous concentration of at least one IgG in, for example, a patient or a biological sample from a patient. In some embodiments, the at least one IgG includes pathogenic IgG. In some embodiments, the at least one IgG includes serum IgG1. In some embodiments, the at least one IgG includes serum IgG2. In some embodiments, the at least one IgG includes serum IgG3. In some embodiments, the at least one IgG includes serum IgG4.

[0140] As used herein in the context of numerical values and ranges, the terms "about" or "approximate" refer to a value or range that is approximate or close to the stated value or range such that the embodiments can be practiced as expected, which will be apparent to those skilled in the art from the teachings contained herein. These terms encompass values that exceed those produced by systematic error. In some embodiments, "about" or "approximate" means plus or minus 10% of the numerical value.

[0141] 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 cause and treatment (Adj INCAT) score in a CIDP patient and / or a sample from a CIDP patient. The Adj INCAT disability score is a measure of activity limitation and consists of two parts: an arm score and a leg score. Based on the level of impairment of the patient's arms and legs, the score for each part ranges from 0 to 5, resulting in an INCAT total score between 0 and 10. In some embodiments, a therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment is the amount required to reduce the 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 relative to the level prior to treatment with the anti-FcRn antibody or antigen. In some embodiments, a therapeutically effective amount of an anti-FcRn antibody or antigen-binding fragment is the amount required to reduce the 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 relative to the level prior to treatment with the anti-FcRn antibody or antigen-binding fragment.

[0142] In various embodiments of the therapeutic methods and uses disclosed herein, the antibody or antigen-binding fragment is administered to a patient at a fixed dose. In various embodiments of the therapeutic methods and uses disclosed herein, the antibody or antigen-binding fragment is administered to a patient at a body weight-based dose (i.e., a dose that depends on the patient's body weight). In various embodiments of the therapeutic methods and uses disclosed herein, the antibody or antigen-binding fragment is administered to a patient at a body surface area (BSA)-based dose (i.e., a dose that depends on the patient's body surface area). In various embodiments, the dose administered to the patient comprises a therapeutically effective amount of the antibody or antigen-binding fragment.

[0143] In some embodiments, the antibody or antigen-binding fragment is administered to the patient at a dose of from about 170 mg to about 1500 mg. In some embodiments, the antibody or antigen-binding fragment is administered to the patient at a dose of from about 300 mg to about 800 mg. In some embodiments, the antibody or antigen-binding fragment is administered to the patient at a dose of about 170 mg, about 200 mg, about 250 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 a week or once every two weeks.

[0144] In some embodiments, the antibody or antigen-binding fragment is administered to the patient at a dose of from about 170 mg to about 300 mg. In some embodiments, the antibody or antigen-binding fragment is administered to the 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.

[0145] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of from 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.

[0146] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of from 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 a patient once a week at a dose of about 340 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a 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 a patient once a week at a dose of about 340 mg 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, or longer). In some embodiments, the antibody or antigen-binding fragment is administered to a patient once a week at a dose of about 340 mg for at least 4 weeks. In some embodiments, the antibody or antigen-binding fragment is administered to a patient once a week at a dose of about 340 mg for at least 7 weeks. In some embodiments, the antibody or antigen-binding fragment is administered to a patient once a week at a dose of about 340 mg for at least 12 weeks.

[0147] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of from 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.

[0148] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of from about 650 mg to about 750 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a 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 a 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 a patient at a dose of about 680 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 680 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient once a week at a dose of about 680 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient as two or more (e.g., two) consecutive subcutaneous injections once a week at a dose of about 680 mg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient once a week at a dose of about 680 mg 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 or longer). In some embodiments, the antibody or antigen-binding fragment is administered to a patient once a week at a dose of about 680 mg for at least 4 weeks. In some embodiments, the antibody or antigen-binding fragment is administered to a patient once a week at a dose of about 680 mg for at least 7 weeks. In some embodiments, the antibody or antigen-binding fragment is administered to a patient once a week at a dose of about 680 mg for at least 12 weeks.

[0149] 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 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.

[0150] 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.

[0151] 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 1290 mg, or about 1300 mg.

[0152] 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.

[0153] In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1 mg / kg to about 2000 mg / kg body weight. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1 mg / kg to about 200 mg / kg, about 200 mg / kg to about 400 mg / kg, about 400 mg / kg to about 600 mg / kg, about 600 mg / kg to about 800 mg / kg, about 800 mg / kg to about 1000 mg / kg, about 1000 mg / kg to about 1200 mg / kg, about 1200 mg / kg to about 1400 mg / kg, about 1400 mg / kg to about 1600 mg / kg, about 1600 mg / kg to about 1800 mg / kg, or about 1800 mg / kg to about 2000 mg / kg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1 mg / kg to about 200 mg / kg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1 mg / kg, about 10 mg / kg, about 20 mg / kg, about 30 mg / kg, about 40 mg / kg, about 50 mg / kg, about 60 mg / kg, about 70 mg / kg, about 80 mg / kg, about 90 mg / kg, about 100 mg / kg, about 110 mg / kg, about 120 mg / kg, about 130 mg / kg, about 140 mg / kg, about 150 mg / kg, about 160 mg / kg, about 170 mg / kg, about 180 mg / kg, about 190 mg / kg, or about 200 mg / kg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1 mg / kg to about 40 mg / kg. In some embodiments, the antibody or antigen-binding fragment is administered to a patient at a dose of about 1 mg / kg, about 5 mg / kg, about 10 mg / kg, about 15 mg / kg, about 20 mg / kg, about 25 mg / kg, about 30 mg / kg, about 35 mg / kg, or about 40 mg / kg.

[0154] The frequency of administering an antibody or antigen-binding fragment as a single agent or in combination with one or more additional therapeutic agents to a patient can be once or more than once. In some embodiments, the antibody or antigen-binding fragment is administered once. In some embodiments, the antibody or antigen-binding fragment is administered multiple times. The interval between doses can be, for example, daily, weekly, bi-weekly, monthly, or annually. The interval can also be irregular, e.g., based on measuring the blood level of the antibody or antigen-binding fragment in the patient to maintain a relatively consistent plasma concentration of the antibody or antigen-binding fragment; based on measuring the level of at least one autoantibody and / or pathogenic antibody (e.g., at least one IgG) to maintain a reduced level of at least one autoantibody and / or pathogenic antibody (e.g., at least one IgG) so as to provide a desired therapeutic or prophylactic effect; and / or based on measuring the level of total serum IgG to maintain a reduced total serum IgG level so as to provide the desired therapeutic or prophylactic effect. The interval can also be irregular, e.g., based on measuring the hemoglobin level to maintain an increase in the hemoglobin level so as to provide the desired therapeutic or prophylactic effect. Alternatively, in some embodiments, the antibody or antigen-binding fragment can be administered as a sustained-release formulation, in which case a lower frequency of administration is required. The dose and frequency can vary depending on the half-life of the antibody or antigen-binding fragment in the patient. The dose and frequency of administration can also vary depending on whether the treatment is prophylactic or therapeutic. In prophylactic applications, relatively low doses can be administered at relatively infrequent intervals over a long period of time. Some patients may continue treatment for the rest of their lives. In therapeutic applications, relatively high doses are sometimes administered at relatively short time intervals until the progression of the disease is alleviated or terminated, and optionally until the patient shows partial or complete improvement of one or more symptoms of the disease. Thereafter, a lower, e.g., prophylactic regimen, can be administered to the patient.

[0155] In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a 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 longer.

[0156] In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a patient as a single dose once.

[0157] 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 longer. In some embodiments, the antibody, antigen binding fragment or pharmaceutical composition is administered to the patient once a week for 6 weeks to 76 weeks, or any time 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 one or more symptoms of CIDP, prevent one or more symptoms of CIDP, reduce the severity of one or more symptoms of CIDP, delay the onset of one or more symptoms of CIDP, and / or reduce the risk of one or more symptoms of CIDP occurring.

[0158] In some embodiments, antibody, Fab or pharmaceutical composition is applied to the patient once a week as a single (i.e., once) subcutaneous injection. In some embodiments, antibody, Fab or pharmaceutical composition is applied to the patient once a week as two or more continuous subcutaneous injections (e.g., two continuous subcutaneous injections). As used herein, the term "continuous (consecutive)" in the context of subcutaneous injection (or other route of administration) refers to two or more subcutaneous injections being applied in succession, but close enough in time to provide desired treatment or preventive effect. In some embodiments, continuous subcutaneous injections are applied in about 30 seconds, in about 1 minute, in about 2 minutes, in about 5 minutes, in about 10 minutes, in about 30 minutes, in about 1 hour, in about 2 hours, or in about 5 hours.

[0159] In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a patient once every two weeks (biweekly). In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a 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 longer. In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a patient once every two weeks for 6 to 76 weeks, or any period therebetween. In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a patient once every two weeks for at least 12 weeks. In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a patient weekly for at least 12 weeks. In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a patient weekly for at least 24 weeks. In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a patient weekly for at least 52 weeks. In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a patient weekly for up to 24 weeks. In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a patient weekly for up to 52 weeks. In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a patient weekly until one or more symptoms of CIDP are sufficiently treated, one or more symptoms of CIDP are prevented, the severity of one or more symptoms of CIDP is reduced, the onset of one or more symptoms of CIDP is delayed, and / or the risk of occurrence of one or more symptoms of CIDP is decreased. 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 as two or more consecutive subcutaneous injections.

[0160] In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a patient once a month. In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a patient once a month for at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 18 months, at least 24 months, at least 30 months, at least 36 months, or longer. In some embodiments, an antibody, antigen-binding fragment, or pharmaceutical composition is administered to a patient once a month until one or more symptoms of CIDP are sufficiently treated, one or more symptoms of CIDP are prevented, the severity of one or more symptoms of CIDP is reduced, the onset of one or more symptoms of CIDP is delayed, and / or the risk of occurrence of one or more CIDP symptoms is reduced. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once a month as a single subcutaneous injection. In some embodiments, the antibody, antigen-binding fragment, or pharmaceutical composition is administered to the patient once a month as two or more consecutive subcutaneous injections.

[0161] In some embodiments of the methods of treatment, uses, and compositions disclosed herein, the therapeutically effective amount of the antibody or antigen-binding fragment is from about 170 mg to about 1500 mg, administered as a single dose once. More specifically, in some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is from about 170 mg to about 300 mg, administered as a single dose once. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is from about 300 mg to about 500 mg, administered as a single dose once. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is from about 500 mg to about 700 mg, administered as a single dose once. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is from about 700 mg to about 900 mg, administered as a single dose once. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is from about 900 mg to about 1100 mg, administered as a single dose once. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is from about 1100 mg to about 1300 mg, administered as a single dose once. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is from about 1300 mg to about 1500 mg, administered as a single dose once.

[0162] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, a therapeutically effective amount of an antibody or antigen-binding fragment is from about 300 mg to about 800 mg, administered as a single dose once. In some embodiments, a therapeutically effective amount of an antibody or antigen-binding fragment is from about 300 mg to about 400 mg, administered as a single dose once. In some embodiments, a therapeutically effective amount of an antibody or antigen-binding fragment is about 340 mg, administered as a single dose once. In some embodiments, a therapeutically effective amount of an antibody or antigen-binding fragment is from about 450 mg to about 550 mg, administered as a single dose once. In some embodiments, a therapeutically effective amount of an antibody or antigen-binding fragment is about 500 mg, administered as a single dose once. In some embodiments, a therapeutically effective amount of an antibody or antigen-binding fragment is from about 700 mg to about 800 mg, administered as a single dose once. In some embodiments, a therapeutically effective amount of an antibody or antigen-binding fragment is about 765 mg, administered as a single dose once. In some embodiments, treatment reduces the patient's total serum IgG level by at least about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50%. In some embodiments, treatment reduces the patient's total serum IgG level by at least about 25%. In some embodiments, treatment reduces the patient's total serum IgG level by at least about 35%. In some embodiments, treatment reduces the patient's total serum IgG level by at least about 45%. In some embodiments, the maximum reduction in the patient's total serum IgG level occurs about 5 days to 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 reduction in the patient's total serum IgG level occurs about 8 days to 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 reduction in total serum IgG level occurs after about 3 to 5 doses (e.g., about 4 doses) of the antibody or antigen-binding fragment or a pharmaceutical composition comprising the antibody or antigen-binding fragment. In some embodiments, 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, treatment increases the patient's hemoglobin level by at least about 10% (e.g., about 10% to about 15%). In some embodiments, treatment increases the patient's hemoglobin level by at least about 20% (e.g., about 20% to about 25%). In some embodiments, treatment increases the patient's hemoglobin level by more than about 20% (e.g., about 25%, about 30%, or more).

[0163] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 170 mg to about 1500 mg, administered once weekly. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 170 mg to about 300 mg, administered once weekly. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 300 mg to about 500 mg, administered once weekly. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 500 mg to about 700 mg, administered once weekly. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 700 mg to about 900 mg, administered once weekly. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 900 mg to about 1100 mg, administered once weekly. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 1100 mg to about 1300 mg, administered once weekly. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 1300 mg to about 1500 mg, administered once weekly.

[0164] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, the therapeutically effective amount of the antibody or antigen-binding fragment is from about 300 mg to about 800 mg, administered once a week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is from about 300 mg to about 400 mg, administered once a week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 340 mg, administered once a week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is from about 650 mg to about 750 mg, administered once a week. In some embodiments, the therapeutically effective amount of the antibody or antigen-binding fragment is about 680 mg, administered once a week. In some embodiments, the treatment reduces the total serum IgG level of the patient 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 total serum IgG level of the patient by at least about 60%. In some embodiments, the treatment reduces the total serum IgG level of the patient by at least about 70%. In some embodiments, the treatment reduces the total serum IgG level of the patient by at least about 80%. In some embodiments, the maximum reduction in the total serum IgG level of the patient occurs at about 20 days to about 30 days after administration of the antibody or antigen-binding fragment or the pharmaceutical composition comprising the antibody or antigen-binding fragment. In some embodiments, the maximum reduction in the total serum IgG level of the patient occurs at about 24 days after administration of the antibody or antigen-binding fragment or the pharmaceutical composition comprising the antibody or antigen-binding fragment. In some embodiments, the maximum reduction in the total serum IgG level occurs after about 3 to 5 doses (e.g., about 4 doses) of the antibody or antigen-binding fragment or the pharmaceutical composition comprising the antibody or antigen-binding fragment. In some embodiments, the treatment increases the hemoglobin level of the patient by at least about 5%, about 10%, about 15%, or about 20% (e.g., from about 5% to about 30%). In some embodiments, the treatment increases the hemoglobin level of the patient by more than about 20%. In some embodiments, after administration once a week for about 1 or 2 weeks (e.g., 680 mg administered once a week), the treatment increases the hemoglobin level of the patient by at least about 10% (e.g., from about 10% to about 15%). In some embodiments, after administration once a week for about 1 or 2 weeks (e.g., 680 mg administered once a week or 340 mg administered once a week), the treatment increases the hemoglobin level of the patient by at least about 20% (e.g., from about 20% to about 25%). In some embodiments, the increase in the hemoglobin level of the patient is maintained (e.g., increased by about 10%, about 20%, or more) throughout the treatment period or a portion thereof. In some embodiments, the increase in the hemoglobin level of the patient (e.g., increased by about 10%, about 20%, or more) is maintained for at least 4 weeks (e.g., at least 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, or longer).

[0165] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 170 mg to about 1500 mg, administered once every two weeks. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 300 mg to about 800 mg, administered once every two weeks. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 170 mg to about 300 mg, administered once every two weeks. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 300 mg to about 500 mg, administered once every two weeks. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 500 mg to about 700 mg, administered once every two weeks. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 700 mg to about 900 mg, administered once every two weeks. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 900 mg to about 1100 mg, administered once every two weeks. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 1100 mg to about 1300 mg, administered once every two weeks. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 1300 mg to about 1500 mg, administered once every two weeks.

[0166] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 170 mg to about 1500 mg, administered once a month. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 300 mg to about 800 mg, administered once a month. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 170 mg to about 300 mg, administered once a month. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 300 mg to about 500 mg, administered once a month. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 500 mg to about 700 mg, administered once a month. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 700 mg to about 900 mg, administered once a month. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 900 mg to about 1100 mg, administered once a month. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 1100 mg to about 1300 mg, administered once a month. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is from about 1300 mg to about 1500 mg, administered once a month.

[0167] In some embodiments of the therapeutic methods, uses, and compositions disclosed herein, a therapeutically effective amount of an antibody or antigen-binding fragment is about 340 mg or about 680 mg, administered once weekly. In some embodiments, the antibody or antigen-binding fragment is administered subcutaneously.

[0168] In some embodiments, relative to the total serum IgG level in the patient and / or sample prior to treatment, after about 1 or 2 weeks of weekly administration, treatment with an antibody or antigen-binding fragment at a dose of about 340 mg or about 680 mg once weekly reduces the level of total serum IgG in the patient and / or sample from the patient by at least about 40% (e.g., about 40% to about 50%). In some embodiments, relative to the total serum IgG level in the patient and / or sample prior to treatment, after about 3 weeks of weekly administration, treatment with an antibody or antigen-binding fragment at a dose of about 340 mg or about 680 mg once weekly reduces the level of total serum IgG in the patient and / or sample from the patient by at least about 60% (e.g., about 60% to about 70%). In some embodiments, relative to the total serum IgG level in the patient and / or sample prior to treatment, after about 5 weeks of weekly administration, treatment with an antibody or antigen-binding fragment at a dose of about 340 mg or about 680 mg once weekly reduces the level of total serum IgG in the patient and / or sample from the patient by at least about 70% (e.g., about 70% to about 80%). In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is about 680 mg, administered once weekly. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is about 680 mg, 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 longer). In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is about 340 mg, administered once weekly. In some embodiments, a therapeutically effective amount of the antibody or antigen-binding fragment is about 680 mg, 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 longer).

[0169] In some embodiments, the antibody or antigen-binding fragment is administered to a 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 a patient in two different doses, e.g., at least one higher dose followed by at least one lower dose. The higher dose (e.g., the higher of two different doses) may be referred to herein as an "inducing" dose, i.e., a dose capable of reducing the level of at least one autoantibody and / or pathogenic antibody (e.g., at least one IgG) in a patient and / or a sample from the patient. The lower dose (e.g., the lower of two different doses) may be referred to herein as a "maintenance" dose, i.e., a dose capable of maintaining a reduced level of at least one autoantibody and / or pathogenic antibody (e.g., at least one IgG) in a patient and / or a sample from the patient after at least one inducing dose of the antibody or antigen-binding fragment (e.g., about 20 - 80% of the pretreatment (pre-induction dose) value). 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 a patient and / or 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) value.

[0170] In some embodiments, the antibody or antigen-binding fragment is administered to a 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 a patient in three different doses, e.g., at least one higher dose (e.g., 680 mg) is administered for a period of time, followed by at least one lower dose (e.g., 340 mg) for a period of time, followed by a third dose for a period of time. In some embodiments, the third dose administered is the same as the higher dose administered (e.g., 680 mg). In some embodiments, the third dose administered is the same as the lower dose administered (e.g., 340 mg). In some embodiments, the third dose administered is about 340 mg per dose or about 680 mg per dose. In some embodiments, the patient receives the lower dose (e.g., 340 mg) during the third dose phase if the patient does not experience a relapse during the administration of the second lower dose (e.g., 340 mg). In some embodiments, if the patient experiences a relapse during the administration of the second lower dose, the higher dose (e.g., 680 mg, administered for at least 4 weeks, at least 12 weeks, or at least 28 weeks) is administered to the patient as part of the third dose period, followed by the lower dose (e.g., 340 mg). In some embodiments, subcutaneous administration is performed once a week.

[0171] In some embodiments, the antibody or antigen-binding fragment is administered to a patient in two or more doses, where the patient has relapsed. In some embodiments, the patient relapses after treatment with at least one maintenance dose. In some embodiments, a relapsed patient is treated with a dose of about 680 mg followed by a dose of about 340 mg. In some embodiments, a relapsed patient is treated with a dose of about 680 mg, administered subcutaneously once a week, for example, for 4 weeks or at least 4 weeks, followed by a dose of about 340 mg administered subcutaneously once a week.

[0172] In some embodiments, the induction and maintenance doses are alternated. For example, a patient may receive an induction dose during a first time period, then a maintenance dose during the first time period, and subsequently, an induction dose during a second time period, optionally followed by a maintenance dose during the second time period. In some embodiments, the cycle of induction and maintenance doses (administering an induction dose for a period of time and then a maintenance dose for a period of time, which is one cycle) is repeated once, twice, three times, four times, five times, six times, seven times, or ten times. In some embodiments, the cycle of induction and maintenance doses is repeated for about 3 months, about 6 months, about 12 months, about 15 months, about 18 months, about 24 months, or longer.

[0173] In some embodiments, at least one higher dose and / or induction dose is about 680 mg / dose or more (e.g., about 700 mg / dose, about 720 mg / dose, about 750 mg / dose, or more). In some embodiments, at least one higher dose and / or induction dose is about 1 dose, about 2 doses, about 3 doses, about 4 doses, or about 5 doses, administered at about 680 mg / dose or more (e.g., about 700 mg / dose, about 720 mg / dose, about 750 mg / dose, or more). In some embodiments, at least one higher dose and / or induction dose is about 3 doses, administered at about 680 mg / dose or more (e.g., about 700 mg / dose, about 720 mg / dose, about 750 mg / dose, or more).

[0174] In some embodiments, at least one higher 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 higher dose and / or induction dose is administered intravenously to the patient. In some embodiments, at least one higher dose and / or induction dose is administered subcutaneously to the patient. In some embodiments, each higher dose is administered to the patient in the form of one or more subcutaneous injections. In some embodiments, each higher dose is administered to the patient in the form of two consecutive subcutaneous injections.

[0175] 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 1 dose, about 2 doses, about 3 doses, about 4 doses, or about 5 doses, at about 340 mg / dose. In some embodiments, at least one lower dose and / or maintenance dose is about 3 doses, at about 340 mg / dose. In some embodiments, at least one lower dose and / or maintenance dose is administered to a patient once, once a week, once every two weeks, or once a month. In some embodiments, at least one lower dose and / or maintenance dose is administered subcutaneously to a patient. In some embodiments, each lower dose is administered to a patient in the form of one or more subcutaneous injections. In some embodiments, each lower dose is administered to a patient in the form of a single subcutaneous injection.

[0176] In various embodiments, the present disclosure also provides a kit for use in the therapeutic applications described herein. In various embodiments, the present disclosure provides a kit for treating or preventing CIDP, which comprises an anti-FcRn antibody or an antigen-binding fragment thereof. In various embodiments, the kit further comprises one or more additional components, including but not limited to: instructions for use; other agents, such as one or more additional therapeutic agents (e.g., one or more standard therapeutic agents); devices, containers, or other materials for preparing the antibody or antigen-binding fragment for therapeutic administration; a pharmaceutically acceptable carrier (e.g., an excipient); and devices, containers, or other materials for administering the antibody or antigen-binding fragment to a patient. In some embodiments, the kit includes a pre-filled syringe that contains a single dose (e.g., a dose provided herein) of the antibody or an antigen-binding fragment thereof and instructions for use. The instructions for use may include guidance for therapeutic applications, including recommended doses and / or modes of administration, e.g., in patients having or suspected of having CIDP. In various embodiments, the kit contains an anti-FcRn antibody or an antigen-binding fragment thereof and instructions for therapeutic use, e.g., the use of the antibody or antigen-binding fragment to treat or prevent CIDP in a patient. In various embodiments, the kit further comprises at least one additional therapeutic agent (e.g., for co-administration with the antibody or antigen-binding fragment). In various embodiments, the antibody or antigen-binding fragment is formulated into a pharmaceutical composition.

[0177] In some embodiments, the anti-FcRn antibody or antigen-binding fragment is produced by expression and purification using recombinant genetic methods. In some embodiments, the polynucleotide sequence encoding the variable regions of the antibody or antigen-binding fragment is produced by expression in separate host cells or by co-expression in a single host cell. Tables 4 and 5 respectively list illustrative polynucleotides encoding the VH and VL, and the heavy and light chains of the anti-FcRn antibody.

[0178] Table 4: Polynucleotide Sequences of the Heavy and Light Chain Variable Domains of Selected Human FcRn Antibodies

[0179]

[0180]

[0181]

[0182] Table 5: Polynucleotide Sequences of the Full-Length Heavy and Light Chains of Selected Human FcRn Antibodies

[0183]

[0184]

[0185]

[0186]

[0187]

[0188] As used herein, the term "recombinant vector" refers to an expression vector capable of expressing a protein of interest in a suitable host cell. The term includes DNA constructs that include the essential regulatory elements operably linked to express a nucleic acid insert.

[0189] As used herein, the term "operably linked" means that a nucleic acid expression control sequence is functionally linked to a nucleic acid sequence encoding a protein of interest to perform a general function. The operable linkage to a recombinant vector can be carried out using genetic recombination techniques well known in the art, and site-specific DNA cleavage and ligation can be readily carried out using enzymes well known in the art.

[0190] Suitable expression vectors may include expression regulatory elements such as promoters, operators, start codons, stop codons, polyadenylation signals, and enhancers, as well as signal sequences for membrane targeting or secretion. The start codon and the stop codon are generally considered to be part of the nucleotide sequence encoding the immunogenic target protein and are necessary for function in an individual to whom the gene construct has been administered and must be in frame with the coding sequence. Promoters can generally be constitutive or inducible. Prokaryotic promoters include but are not limited to the 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 (such as the HIV long terminal repeat (LTR) promoter), Moloney virus promoter, cytomegalovirus (CMV) promoter, Epstein-Barr virus (EBV) promoter, Rous sarcoma virus (RSV) promoter, and promoters from human genes such as human β-actin, human hemoglobin, human muscle creatine, and human metallothionein. The expression vector may include a selectable marker that allows selection of host cells containing the vector. Genes encoding products that confer a selectable phenotype, such as resistance to a drug, a nutrient requirement, or resistance to a cytotoxic agent or surface protein expression, can be used as general selectable markers. Since only cells expressing the selectable marker can survive in an environment treated with a selective reagent, transformed cells can be selected. In addition, a replicable expression vector may include an origin of replication, i.e., a specific nucleic acid sequence that initiates replication. Recombinant expression vectors that can be used include various vectors such as plasmids, viruses, and cosmids. The type of recombinant vector is not limited, and the recombinant vector can function to express the desired gene and produce the desired protein in various host cells such as prokaryotic and eukaryotic cells. In some embodiments, a vector that is capable of producing large amounts of an exogenous protein similar to the native protein while having strong expression ability (where the promoter exhibits strong activity) is used.

[0191] A variety of host / 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 papillomavirus, adenovirus, adeno-associated virus, cytomegalovirus, and retroviruses. Expression vectors that can be used for bacterial hosts include bacterial plasmids such as pET, pRSET, pBluescript, pGEX2T, pUC, col E1, pCR1, pBR322, pMB9 and their derivatives, plasmids with a broader host range such as RP4, phage DNAs represented by various phage λ derivatives (such as gt10, gt11 and NM989), and other DNA phages such as M13 and filamentous single-stranded DNA phages. Expression vectors useful in yeast cells include the 2μm plasmid and its derivatives. A vector useful in insect cells is pVL941.

[0192] In some embodiments, a recombinant vector is introduced into a host cell to form a transformant. Suitable host cells include: prokaryotic cells such as Escherichia coli (E. coli), 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).

[0193] In some embodiments, the host cell is derived from a plant or an animal (e.g., a mammal), and examples thereof include, but are 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.

[0194] Transfection or transformation into a host cell can include any method that can introduce nucleic acids into an organism, cell, tissue, or organ, and as known in the art, can be carried out using appropriate standard techniques selected according to the type of host cell. The methods include but are not limited to: electroporation, protoplast fusion, calcium phosphate (CaPO4) precipitation, calcium chloride (CaCl2) precipitation, agitation with silicon carbide fibers, and agrobacterium-, PEG-, dextran sulfate-, lipofectamine-, and desiccation / inhibition-mediated transformation.

[0195] By culturing the transformant containing the recombinant vector in a nutrient medium, anti-FcRn antibodies or antigen-binding fragments can be produced in large quantities, and the medium and culture conditions used can be selected according to the type of host cell. During the culture process, conditions including temperature, pH of the medium, and culture time can be controlled to be suitable for cell growth and large-scale protein production. The antibodies or antigen-binding fragments produced by the recombinant methods described herein can be collected from the medium or cell lysates and can be separated and purified by conventional biochemical separation techniques (Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory Press (1989); Deutscher, Guide to Protein Purification Methods Enzymology, Vol. 182. 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, immunoaffinity chromatography, size exclusion chromatography, etc.), isoelectric focusing, and various modifications and combinations thereof. In some embodiments, protein A is used to separate and purify the antibodies or antigen-binding fragments.

[0196] Examples

[0197] Hereinafter, the present disclosure will be described in more detail with reference to the examples. It will be apparent to those of ordinary skill in the art that these examples are for illustrative purposes only and should not be construed as limiting the scope of the present disclosure.

[0198] Example 1: Clinical Study of Batoclimab in the Treatment of CIDP

[0199] This example describes a phase 2b, multi-center, randomized, quadruple-blind, placebo-controlled study of Batoclimab treatment in adult participants with active CIDP. The clinical trial schematic diagram is asFigure 1 As shown. Approximately 277 patients will be recruited.

[0200] Four groups (designated as Group A, B, C, or D) were defined based on their baseline CIDP treatment and whether they met the diagnostic definitions according to the EAN / PNS criteria (Groups A, B, and C) or clinical criteria (Group D) at screening: Group A, immunoglobulin (IVIg or SCIg) therapy or PLEX; Group B, chronic systemic corticosteroids (i.e., pulsed or daily use); Group C, untreated (i.e., newly diagnosed patients or patients who were stable after previous treatment but are currently deteriorating); Group D, immunoglobulin (IVIg or SCIg) therapy or PLEX, which meets the CIDP clinical criteria but does not meet the complete CIDP diagnostic criteria according to the EAN / PNS CIDP diagnosis and treatment guidelines.

[0201] Batlomab was formulated as a 340 mg prefilled syringe (170 mg / mL, 2 mL), containing an aqueous solution of 340 mg batlomab, 25.16 mg L-histidine hydrochloride, 12.416 mg L-histidine, 42.14 mg L-arginine hydrochloride, and 0.4 mg polysorbate 20. The placebo formulation had the same buffers and surfactants (without batlomab).

[0202] Participants in Group A, B, or D will enter a washout period of up to 12 weeks, during which their standard treatment therapy will be stopped or tapered. Participants in Group A, B, or D who do not deteriorate at the end of the washout period (Week 0) will withdraw from the study. Participants who meet the deterioration criteria and those who enter the Group C study and do not enter the washout period will be randomly assigned to receive 680 mg or 340 mg of batlomab subcutaneously once a week (for 12 weeks) in Phase 1. Non-responders who complete Phase 1 will withdraw from the study after completing the 12-week and subsequent 4-week follow-up. Phase 1 non-responders who require protocol-disabled rescue treatment before Week 12 will discontinue batuzumab and may resume standard treatment; these participants will be encouraged to continue in the study for the 12-week safety follow-up and follow-up visits.

[0203] In Period 2 (up to 24 weeks), participants were randomly assigned to placebo or 340 mg of bartolimab, and each drug was administered weekly by subcutaneous injection. Participants who relapsed in Period 2 or completed Period 2 without relapse would be eligible to participate in the Long-Term Extension study. After Period 2 was the Long-Term Extension (LTE) period (up to 52 weeks). In the LTE period, participants who relapsed in Period 2 received 680 mg of bartolimab by subcutaneous injection once a week for 4 weeks, and then 340 mg of bartolimab by subcutaneous injection once a week. In the LTE period, participants who did not relapse in Period 2 received 340 mg of bartolimab by subcutaneous injection once a week.

[0204] Purpose

[0205] The primary objective of this trial was to evaluate the efficacy of bartolimab compared with placebo in maintaining clinical response, which was evaluated by the Adjusted Inflammatory Neuropathy Cause and Treatment Score (Adj INCAT) at screening in participants receiving immunoglobulin (IVIg or SCIg) or plasma exchange (PLEX) for the treatment of CIDP.

[0206] The secondary objectives were: (1) to evaluate the efficacy of bartolimab compared with placebo in maintaining clinical response at screening in participants receiving immunoglobulin (IVIg or SCIg) or plasma exchange (PLEX) for the treatment of CIDP; (2) to evaluate the efficacy of bartolimab compared with placebo in maintaining clinical response at screening in patients receiving any treatment for CIDP; (3) to evaluate the efficacy of bartolimab in maintaining clinical response regardless of the history of CIDP treatment.

[0207] Inclusion criteria:

[0208] 1. Age > 18 years at the screening visit.

[0209] 2. Meet the clinical diagnostic criteria for typical CIDP or one of the following CIDP variants: multifocal CIDP, focal CIDP, or motor CIDP, in accordance with the CIDP Diagnosis and Treatment Guidelines of EAN / PNS. The clinical criteria for typical CIDP and variants are as follows (any of the following criteria must be met):

[0210] a. Typical CIDP: All of the following conditions:

[0211] - Progressive or recurrent, symmetric proximal and distal muscle weakness in the upper and lower extremities, and sensory involvement in at least two extremities (at any point in the disease process)

[0212] - Developed for at least 8 weeks

[0213] - Loss or reduction of tendon reflexes in all limbs

[0214] b. Variant CIDP: One of the following, but otherwise the same as typical CIDP (tendon reflexes in unaffected limbs may be normal):

[0215] - Multifocal CIDP: Recorded multifocal sensory loss and muscle weakness, usually asymmetric, predominantly in the upper limbs

[0216] - Focal CIDP: Sensory loss and muscle weakness occur in only one limb

[0217] - Motor CIDP: Motor symptoms and signs without sensory impairment

[0218] Groups A and B:

[0219] 3. According to the EAN / PNS guidelines for the diagnosis and treatment of CIDP, electrodiagnostic test results that support the diagnosis of CIDP (must meet criterion 3(a) or 3(b)):

[0220] a. Motor nerve conduction criteria strongly supportive of demyelination.

[0221] b. Weak motor nerve conduction criteria supportive of demyelination, and two or more of the following additional diagnostic criteria:

[0222] - Objective improvement in an empirical trial of immunoglobulin therapy, plasma exchange (PLEX), or corticosteroid therapy.

[0223] - Diagnostic imaging by ultrasound or magnetic resonance imaging (MRI) supports the diagnosis of CIDP by showing nerve enlargement.

[0224] - Cerebrospinal fluid (CSF) shows albuminocytologic dissociation (i.e., elevated CSF protein level [defined as >70 mg / dL, or >10 mg / dL above age for people 60 years and older] while CSF white blood cell [WBC] level is normal).

[0225] mg / dL] while the cerebrospinal fluid white blood cell [WBC] level is normal).

[0226] - Nerve biopsy shows features supportive of the diagnosis of CIDP, such as edema, demyelination, and / or onion bulb formation.

[0227] For Groups A and D only:

[0228] 4. At the screening visit, currently receiving immunoglobulin therapy (IVIg or SCIg) or PLEX for CIDP for at least 3 months. Note: Participants receiving chronic systemic corticosteroids in combination with immunoglobulin therapy or PLEX are allowed only if the corticosteroid dose has been stable and ≤ 10 mg / day of prednisone / prednisolone or equivalent during the washout period and throughout the participation in Periods 1 and 2. Participants taking other immunosuppressive drugs are not excluded, but must discontinue these drugs after entering the washout.

[0229] 5. Documented response to immunoglobulin therapy or PLEX prior to the screening visit (must meet one of the following criteria (a), (b), (c), or (d)):

[0230] a. A trial of withdrawal from immunoglobulin therapy or PLEX (or reduction in dose or frequency) was conducted within 5 years prior to the screening visit, and subsequent worsening of symptoms was documented.

[0231] b. An increase in therapy (i.e., an increase in the dose or frequency of immunoglobulin therapy or PLEX) was requested within 12 months prior to the screening visit, and improvement in signs and symptoms was documented.

[0232] c. After treatment initiation and initial titration, maintain an INCAT score of 0 or 1 (or a clinical history consistent with an INCAT score of 0 or 1) without an increase in therapy (i.e., without an increase in the dose or frequency of immunoglobulin therapy or PLEX; and no increase in corticosteroids is required in the treatment regimen).

[0233] a. Note: Participants meeting criterion (c) must have an INCAT score of 0 or 1 at the screening visit.

[0234] d. An empirical trial of immunoglobulin treatment or PLEX documented improvement.

[0235] For Group B only:

[0236] 6. At the screening visit, receiving chronic, stable-dose systemic corticosteroids (i.e., daily or pulsed regimen) for the treatment of CIDP (must meet one of the following criteria (a) or (b)):

[0237] a. Receiving chronic oral corticosteroids equivalent to 20 - 40 mg / day of prednisone / prednisolone (including alternate-day or similar regimens), and willing to follow a dose taper requirement during the washout period. If the participant is receiving a dose below 20 mg / day, see the note below.

[0238] Note: A stable dose is considered to be an excursion of ≤ 2.5 mg in the daily dose of prednisone or prednisone equivalent within ≥ 3 months prior to the screening visit.

[0239] Note: Participants on a maintenance steroid dose of less than 20 mg / day of prednisolone / prednisone or equivalent (including alternate-day or similar regimens) may be considered eligible if they meet inclusion criteria 2(a) and 3(a) and after discussion with the sponsor's medical monitor.

[0240] b. Receiving a chronic pulsed corticosteroid treatment regimen defined as ≥ 100 mg / day of prednisolone / prednisone equivalent (i.e., intravenous [IV] / intramuscular [IM] or oral [PO]), with a minimum interval of ≥ 3 weeks between pulses, and willing to discontinue pulsed treatment at the start of washout.

[0241] Note: A stable dose is considered to be a repeating cycle without the need for dose adjustment within ≥ 3 months prior to the screening visit to maintain disease control.

[0242] 7. A documented response to any first-line standard treatment for CIDP (immunoglobulin therapy, corticosteroids, or PLEX) (must meet one of the following criteria (a), (b), (c), or (d)):

[0243] a. A trial in which treatment was discontinued (or dose or frequency reduced) from immunoglobulin therapy, corticosteroids, or PLEX within 5 years prior to the screening visit and subsequent worsening of symptoms was documented.

[0244] b. An increase in corticosteroid therapy (i.e., increase in corticosteroid dose or frequency) was requested within 12 months prior to the screening visit and improvement in signs and symptoms was documented.

[0245] c. The INCAT score was maintained at 0 or 1 (or a clinical history consistent with an INCAT score of 0 or 1) after treatment initiation and initial titration, without the need for additional therapy (i.e., without the need to increase corticosteroid dose or frequency).

[0246] Note: Participants meeting criterion (c) must have an INCAT score of 0 or 1 at the screening visit.

[0247]

[0248] d. An improvement was documented in an empirical trial of immunoglobulin therapy, PLEX, or corticosteroids.

[0249] For Group C only:

[0250] ​8. CIDP was diagnosed according to the EAN / PNS guidelines for the diagnosis and treatment of CIDP (van den Bergh et al., 2021) based on clinical criteria and motor nerve conduction criteria strongly supportive of demyelination (i.e., motor nerve conduction criteria weakly supportive of demyelination are insufficient to be diagnostic evidence for entry into Group C).

[0251] 9. Not currently receiving treatment for CIDP at the screening visit (must meet either criterion (a) or (b) below):

[0252] a. Has not yet received treatment.

[0253] b. Has a history of prior immunoglobulin therapy (IVIg or SCIg), corticosteroids, or PLEX treatment, with the medication discontinued for at least 3 months and no more than 24 months prior to the screening visit.

[0254] 10. There is documented evidence of clinical worsening of CIDP within 3 months prior to the screening visit, requiring initiation or re-initiation of treatment.

[0255] 11. INCAT score ≥ 2 at screening and the first-stage baseline visit.

[0256] Note: Participants with an INCAT score of 2 at study entry must have obtained that score solely from the leg disability score; for participants with an INCAT score ≥ 3 at study entry, there are no specific requirements for the arms or legs.

[0257] 12. Additional inclusion criteria are defined in the protocol.

[0258] Exclusion criteria:

[0259] 1. Presence of immunoglobulin M (IgM) paraproteinemia, with or without anti-myelin-associated glycoprotein antibodies.

[0260] 2. Having distal CIDP, sensory CIDP, or suspected of having autoimmune nodopathy according to the EAN / PNS guidelines for the diagnosis and treatment of CIDP.

[0261] 3. Having polyneuropathy of etiologies other than CIDP, including but not limited to:

[0262] a. Multifocal motor neuropathy

[0263] b. Hereditary demyelinating polyneuropathy

[0264] c. Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes syndrome (i.e.,

[0265] POEMS)

[0266] d. Lumbar radiculopathy

[0267] e. Systemic diseases, including vitamin deficiency syndromes and paraneoplastic neuropathy

[0268] f. Caused by drugs or toxins 4. Suffering from diabetes mellitus (DM) and meeting any of the following criteria:

[0269] a.DM is diagnosed earlier than CIDP

[0270] b. Ever required daily insulin therapy

[0271] c. DM lasts for 5 years or longer

[0272] d. Evidence of microvascular complications of diabetes, including

[0273] e. Retinopathy or nephropathy

[0274] 5. History of spinal cord disease or evidence of central demyelination.

[0275] 6. Currently receiving long-term oral corticosteroid monotherapy at a dose >40 mg / day of prednisolone / prednisone or its equivalent at the screening visit.

[0276] 7. Currently receiving long-term oral corticosteroids at a dose >10 mg / day of prednisone or equivalent combined with immunoglobulin therapy or PLEX at the screening visit.

[0277] 8. Additional exclusion criteria are defined in the protocol.

[0278] Endpoint:

[0279] The primary endpoint was the proportion of participants who remained relapse-free at Week 36, which was sustained at the 1-week follow-up visit, with relapse defined as a worsening (increase) of ≥1 point in the Adj INCAT score from the Period 2 baseline at any time point during Period 2.

[0280] Secondary endpoints include:

[0281] -Phase 2 / Group A:

[0282] o-Time to first relapse relative to period 2 baseline

[0283] o-Change from Period 2 Baseline to Week 36:

[0284] ■Adj INCAT score

[0285] ■ Inflammatory Rasch-built Overall Disability Scale (I-RODS)

[0286] ■ Average grip strength

[0287] ■ Medical Research Council (MRC) total score

[0288] ■ Overall Neuropathy Limitation Scale (ONLS)

[0289] - Phase 2 / Combination of Groups A and B:

[0290] o - Change from Phase 2 baseline to Week 36:

[0291] ■ Adj INCAT score

[0292] ■ I-RODS

[0293] ■ Average grip strength

[0294] ■ MRC total score

[0295] ■ ONLS

[0296] - Phase 2 / Combination of Groups A, B and C:

[0297] - Proportion of participants remaining relapse-free at Week 36

[0298] Although the present disclosure has been described in detail with reference to specific features, it will be apparent to those skilled in the art that the description is for illustrative purposes only and does not limit the scope of the present disclosure. Accordingly, the substantial scope of the present disclosure will be defined by the appended claims and their equivalents.

Claims

1. A method for treating CIDP in a patient in need thereof, comprising administering to the patient a first therapeutically effective amount of an anti-FcRn antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment comprises: (a) Heavy chain variable region, comprising: HCDR1 comprising the amino acid sequence shown in SEQ ID No: 27, HCDR2 comprising the amino acid sequence shown in SEQ ID No: 28, and HCDR3 comprising the amino acid sequence shown in SEQ ID No: 29; and light chain variable region, comprising: LCDR1 comprising the amino acid sequence shown in SEQ ID No: 30, LCDR2 comprising the amino acid sequence of SEQ ID No: 31, and LCDR3 comprising the amino acid sequence shown in SEQ ID No: 32; or (b) Heavy chain variable region, comprising: HCDR1 comprising the amino acid sequence shown in SEQ ID No: 49, HCDR2 comprising the amino acid sequence shown in SEQ ID No: 22, and HCDR3 comprising the amino acid sequence shown in SEQ ID No: 23; and light chain variable region, comprising: LCDR1 comprising the amino acid sequence shown in SEQ ID No: 50, LCDR2 comprising the amino acid sequence shown in SEQ ID No: 25, and LCDR3 comprising the amino acid sequence shown in SEQ ID No:

26.

2. The method according to claim 1, wherein the antibody or antigen-binding fragment comprises: (a) Heavy chain variable region, which comprises an amino acid sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to the sequence shown in SEQ ID No: 6; and light chain variable region, which comprises an amino acid sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to the sequence shown in SEQ ID No: 16; or (b) Heavy chain variable region, which comprises an amino acid sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to the sequence shown in SEQ ID No: 51; and light chain variable region, which comprises an amino acid sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to the sequence shown in SEQ ID No:

52.

3. The method according to claim 1, wherein the antibody or antigen-binding fragment comprises: (a) Heavy chain variable region comprising the sequence shown in SEQ ID NO: 6; and light chain variable region comprising the sequence shown in SEQ ID No: 16; or (b) Heavy chain variable region comprising the sequence shown in SEQ ID No: 51; and light chain variable region comprising the sequence shown in SEQ ID No:

52.

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

4.

5. The method according to claim 4, wherein the K D is measured by surface plasmon resonance (SPR).

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

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

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

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

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

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

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

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

14. The method according to claim 13, wherein the second therapeutically effective amount is 340 mg.

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

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

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

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

19. The method according to any one of claims 16-18, wherein the third therapeutically effective amount is administered for 4 weeks, 12 weeks or 28 weeks.

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

21. A method of treating CIDP in a patient in need thereof, comprising administering to the patient a first therapeutically effective amount of an anti-FcRn antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment comprises: (a) Heavy chain variable region, which contains: HCDR1 comprising the amino acid sequence shown in SEQ ID NO: 27, HCDR2 comprising the amino acid sequence shown in SEQ ID No: 28, and HCDR3 comprising the amino acid sequence shown in SEQ ID No: 29; and light chain variable region, which contains: LCDR1 comprising the amino acid sequence shown in SEQ ID NO: 30, LCDR2 comprising the amino acid sequence of SEQ ID No: 31, and LCDR3 comprising the amino acid sequence shown in SEQ ID No: 32; or (b) Heavy chain variable region, comprising: HCDR1 including the amino acid sequence shown in SEQ ID NO: 49, HCDR2 including the amino acid sequence shown in SEQ ID NO: 22, and HCDR3 including the amino acid sequence shown in SEQ ID NO: 23; and light chain variable region, comprising: LCDR1 including the amino acid sequence shown in SEQ ID NO: 50, LCDR2 including the amino acid sequence of SEQ ID NO: 25, and LCDR3 including the amino acid sequence shown in SEQ ID NO: 26; and wherein a first therapeutically effective amount of the antibody or antigen-binding fragment thereof is 340 mg or 680 mg, administered subcutaneously once a week, optionally for about 12 weeks or longer.

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

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

24. The method according to any one of claims 1-23, wherein the patient is human.

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