CN117120092A

CN117120092A - Compositions and methods for treating pediatric myasthenia gravis

Info

Publication number: CN117120092A
Application number: CN202280027956.3A
Authority: CN
Inventors: S·布莱克; S·拉姆钱德伦; Y·朱
Original assignee: Momenta Pharmaceuticals Inc
Current assignee: Momenta Pharmaceuticals Inc
Priority date: 2021-04-12
Filing date: 2022-04-12
Publication date: 2023-11-24

Abstract

Provided herein are compositions and methods for treating pediatric myasthenia gravis using compositions comprising anti-FcRn antibodies.

Description

Compositions and methods for treating pediatric myasthenia gravis

Cross Reference to Related Applications

The present application claims priority from U.S. patent application Ser. No. 63/173,919, filed on 12 months 4 and 2021, U.S. provisional application Ser. No. 63/219,155, filed on 7 months 7 and 2022, U.S. provisional application Ser. No. 63/266,880, filed on 18 months 1 and 2022, each of which provisional applications is hereby incorporated by reference in its entirety.

Sequence listing

The present application comprises a sequence listing that has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. The ASII copy was created at 2022, 4, 7, named 258199_001202_st25.Txt, and was 26,081 bytes in size.

Technical Field

The present application relates to the treatment of pediatric patients suffering from myasthenia gravis.

Background

Myasthenia Gravis (MG) is a rare heterogeneous neuromuscular disease characterized by fluctuating, fatigued muscle weakness with an prevalence of 15 to 25 per 100,000 individuals and a annual prevalence of 0.8 to 1 per 100,000 individuals. Weakness generally affects the eyes, medulla oblongata, proximal, neck and respiratory muscles, fluctuating throughout the day and worsening with fatigue, repetitive activity, heat, infection and stress. In most cases, the initial symptoms are ocular and include ptosis and presbyopia, but within 2 to 3 years of onset, the disease usually worsens and other muscles are affected; this is called whole body MG (gMG). Additional symptoms often include difficulty chewing, dysphagia, dysarthria, hypophonia, dyspnea, inability to keep the mouth closed, "growling" expressions when smiling is attempted, sadness or somnolence is present, difficulty in keeping the head upright, and weakness in the hands and feet. Disease progression is associated with a relatively high incidence of aspiration, an increased incidence of respiratory tract infections and falls, and side effects of immunosuppressive therapy. Furthermore, respiratory muscle weakness can lead to a muscle weakness crisis, which can be life threatening and requires hospitalization, mechanical ventilation, tube feeding, fast acting immunosuppressants and intensive care. Myasthenia crisis is also associated with other infections and cardiovascular complications that increase morbidity and mortality risk. There is a significant unmet need for treatment options for patients with MG. The embodiments provided herein meet these needs and others.

Disclosure of Invention

In some embodiments, a method of treating pediatric myasthenia gravis in a pediatric patient in need thereof is provided. In some embodiments, the method comprises administering an initial loading dose of about 30mg/kg to about 60mg/kg of an anti-FcRn antibody, followed by a maintenance dose of about 15mg/kg to about 30mg/kg of an anti-FcRn antibody, wherein the anti-FcRn antibody comprises: heavy chains comprising HCDR1 of SEQ ID NO. 6, HCDR2 of SEQ ID NO. 7 and HCDR3 of SEQ ID NO. 8; a light chain comprising LCDR1 of SEQ ID NO. 3, LCDR2 of SEQ ID NO. 4 and LCDR3 of SEQ ID NO. 5; wherein the administration reduces serum IgG of the patient by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of baseline serum IgG, and wherein the pediatric myasthenia is selected from temporary neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome, or any combination thereof.

In some embodiments, a pharmaceutical composition comprising an anti-FcRn antibody for administration to a pediatric patient suffering from pediatric myasthenia gravis is provided. In some embodiments, a pharmaceutical composition comprising an anti-FcRn antibody is administered intravenously or subcutaneously to a pediatric patient at an initial loading dose of about 30mg/kg to about 60mg/kg, followed by administration of a maintenance dose of about 15mg/kg to about 30mg/kg of the anti-FcRn antibody; and the anti-FcRn antibody comprises a heavy chain comprising HCDR1 of SEQ ID No. 6, HCDR2 of SEQ ID No. 7 and HCDR3 of SEQ ID No. 8; and a light chain comprising LCDR1 of SEQ ID NO. 3, LCDR2 of SEQ ID NO. 4, and LCDR3 of SEQ ID NO. 5, wherein the pediatric myasthenia gravis is selected from the group consisting of transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome, or any combination thereof.

Drawings

FIG. 1 is a graph showing modeled results designed to predict IgG reduction and MG-ADL improvement at 15MG/kg and 30MG/kg q2w maintenance doses in adult patients with gMG.

FIG. 2 is a graph showing modeled results designed to predict IgG reduction and MG-ADL improvement with a 30MG/kg loading dose in an adult patient with gMG.

Detailed Description

The present application incorporates by reference the following applications in their entirety: PCT application number PCT/US2021/058188 filed on month 11 of 2022, US provisional application number 63/110,884 filed on month 11 of 2020, US provisional application number 63/137,972 filed on month 15 of 2021, US provisional application number 63/173,126 filed on month 4 of 2021, US provisional application number 63/173,919 filed on month 4 of 2021, US provisional application number 63/174,423 filed on month 13 of 2021, US provisional application number 63/175,440 filed on month 4 of 2021, US provisional application number 63/203,075 filed on month 7 of 2021, US provisional application number 63/203,077 filed on month 7 of 2021, US provisional application number 63/219,155 filed on month 7 of 2021, and US provisional application number 63/266,880 filed on month 18 of 2022.

Myasthenia gravis is caused by pathogenic autoantibodies that impair cholinergic transmission of postsynaptic membranes at neuromuscular junctions and impair or prevent muscle contraction. In about 85% of cases, circulating antibodies target the acetylcholine receptor (AChR) itself. Up to half of the remaining 15% of patients have antibodies against muscle-specific tyrosine kinase (MuSK), an enzyme critical for neuromuscular junction formation and human-agrin-induced AChR aggregation, while about 7% to 8% of patients have neither anti-AChR nor anti-MuSK antibodies and have historically been considered "seronegative". In the latter group, approximately 10% have pathogenic autoantibodies to lipoprotein-related protein receptor 4, an end-plate protein, which acts as a human collectin receptor with MuSK and is necessary for AChR aggregation and normal neuromuscular junction formation.

Embodiments of methods of treating myasthenia gravis and related symptoms or conditions associated therewith are provided. In some embodiments, a pediatric subject suffering from myasthenia gravis is treated with an antibody directed against the human neonatal Fc receptor (FcRn). anti-FcRn antibodies can be used, for example, to promote clearance of autoantibodies in a pediatric subject, to inhibit antigen presentation in a pediatric subject, to block an immune response in a pediatric subject (e.g., to block activation of an immune response based on an immune complex), or to treat an immune disorder (e.g., an autoimmune disorder) in a pediatric subject.

In some embodiments, the anti-FcRn antibody is nicalimab (nipocalimab), which may also be referred to as M281. In some embodiments, the term "nicarbazin" and the term "M281" are used interchangeably. The nica Li Shan antibody is an antibody against human neonatal Fc (FcRn). The NICAR Li Shan antibodies are described in U.S. Pat. No. 10676526, PCT publication No. WO 2020/0232310, PCT publication No. WO2020/018910, and PCT publication No. WO2021/022249, each of which is hereby incorporated by reference in its entirety.

The term "antibody" is used herein in its broadest sense and covers a variety of antibody structures including, but not limited to, monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies) scFV, nanobodies, VHHs, and antibody fragments, so long as they exhibit FcRn antigen-binding activity.

In addition, the term antibody or antibody molecule as used herein refers to a polypeptide, such as an immunoglobulin chain or fragment thereof, comprising at least one functional immunoglobulin variable domain sequence. Antibody molecules encompass antibodies (e.g., full length antibodies) and antibody fragments. In some embodiments, the antibody molecule comprises an antigen binding or functional fragment of a full length antibody or full length immunoglobulin chain. For example, a full-length antibody is an immunoglobulin (Ig) molecule (e.g., an IgG antibody) that occurs naturally or is formed by the process of recombination of normal immunoglobulin gene fragments. In embodiments, an antibody molecule refers to an immunologically active antigen-binding portion of an immunoglobulin molecule, such as an antibody fragment. Antibody fragments (e.g., functional fragments) comprise a portion of an antibody, such as Fab, fab ', F (ab') 2, F (ab) 2, variable fragment (Fv), domain antibody (dAb), or single chain variable fragment (scFv). The functional antibody fragment binds to the same antigen as that recognized by the intact (e.g., full length) antibody. The term "antibody fragment" or "functional fragment" also includes isolated fragments consisting of variable regions, such as "Fv" fragments consisting of variable regions of heavy and light chains or recombinant single chain polypeptide molecules ("scFv proteins") in which the light and heavy chain variable regions are linked by a peptide linker. In some embodiments, the antibody fragment does not include an antibody moiety that does not have antigen binding activity, such as an Fc fragment or a single amino acid residue. Exemplary antibody molecules include full length antibodies and antibody fragments, such as dAb (domain antibodies), single chain, fab 'and F (ab') 2 fragments, and single chain variable fragments (scFv).

Immunoglobulin chains exhibit the same general structure of relatively conserved Framework Regions (FR) joined by three hypervariable regions (also known as complementarity determining regions or CDRs). The CDRs from the two chains of each pair are aligned by a framework region, enabling binding to a specific epitope. From N-terminal to C-terminal, the light and heavy chains comprise the domains FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. Amino acid assignment to each domain is defined according to Kabat Sequences of Proteins of Immunological Interest (National Institutes ofHealth, bethesda, md. (1987 and 1991)). In some embodiments, the antibodies provided herein comprise the same FR and different CDRs. In some embodiments, the antibodies provided herein comprise the same CDR and different FR. In some embodiments, the mutation in the FR is in the heavy chain. In some embodiments, the mutation in FR is in FR1 of the heavy chain. In some embodiments, the mutation in FR is in FR2 of the heavy chain. In some embodiments, the mutation in FR is in FR3 of the heavy chain. In some embodiments, the mutation in FR is in FR4 of the heavy chain. In some embodiments, the mutation in the FR is in the light chain. In some embodiments, the mutation in FR is in FR1 of the light chain. In some embodiments, the mutation in FR is in FR2 of the light chain. In some embodiments, the mutation in FR is in FR3 of the light chain. In some embodiments, the mutation in FR is in FR4 of the light chain. In some embodiments, mutations in FR are in the heavy and light chains. In some embodiments, the mutation in the FR is in any one or more of the FR of the heavy and light chain.

The term "antibody molecule" also encompasses whole or antigen-binding fragments of a domain or single domain antibody, which may also be referred to as "sdAb" or "VHH". Domain antibodies comprise V which can function as independent antibody fragments _H Or V _L . In addition, domain antibodies include heavy chain-only antibodies (hcabs). Domain antibodies also include the CH2 domain of IgG as a basic scaffold into which CDR loops are grafted. It can also be generally defined as a polypeptide or protein comprising an amino acid sequence consisting of four framework regions interrupted by three complementarity determining regions. This is denoted as FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. sdabs may be produced in camelids (such as llamas), but may also be produced synthetically using techniques well known in the art. Numbering of amino acid residues of sdabs or polypeptides is according to the general numbering of VH domains given by Kabat et al. According to this numbering, FR1 of the sdAb comprises the amino acid residues at positions 1 to 30, CDR1 of the sdAb comprises the amino acid residues at positions 31 to 36, FR2 of the sdAb comprises the amino acid residues at positions 36 to 49, CDR2 of the sdAb comprises the amino acid residues at positions 50 to 65, FR3 of the sdAb comprises the amino acid residues at positions 66 to 94, CDR3 of the sdAb comprises the amino acid residues at positions 95 to 102, and FR4 of the sdAb comprises the amino acid residues at positions 103 to 113. Domain antibodies are also described in PCT publication nos. WO2004041862 and WO2016065323, each of which is hereby incorporated by reference.

In some embodiments, as provided herein, an antibody molecule can be monospecific (e.g., monovalent or divalent), bispecific (e.g., divalent, trivalent, tetravalent, pentavalent, or hexavalent), trispecific (e.g., trivalent, tetravalent, pentavalent, hexavalent), or have higher specificity (e.g., tetraspecific), and/or higher valency beyond hexavalent. An antibody molecule may comprise a functional fragment of a light chain variable region and a functional fragment of a heavy chain variable region, or the heavy and light chains may be fused together into a single polypeptide.

As used herein, the term "fusion" or "linkage" when used in reference to proteins having different domains or heterologous sequences means that the protein domains are part of the same peptide chain, which are linked to each other by peptide bonds or other covalent bonds. The domains or segments may be directly linked or fused to each other, or another domain or peptide sequence may be between the two domains or sequences, and such sequences will still be considered fused or linked to each other. In some embodiments, the various domains or proteins provided herein are directly linked or fused to each other or to a linker sequence, such as a glycine/serine, glycine/alanine linker or other types of peptide linkers commonly known to link two domains together. Two peptide sequences are directly linked if they are directly linked to each other, or indirectly linked if there is a linker or other structure linking the two regions. The linker may be directly linked to two different peptide sequences or domains.

As used herein, the terms "variable region" and "variable domain" refer to portions of the light and heavy chains of an antibody that include the amino acid sequences of complementarity determining regions (CDRs, e.g., CDR L1, CDR L2, CDR L3, CDR H1, CDR H2, and CDR H3) and Framework Regions (FR). Amino acid positions assigned to CDRs and FR according to the methods used in the present disclosure are according to the Kabat definition (Sequences of Proteins of Immunological Interest, 5 th edition Public Health Service, national Institutes of Health, bethesda, MD. (1991)). Using this numbering system, the actual linear amino acid sequence may comprise fewer or additional amino acids corresponding to shortening or insertion of CDRs (further defined herein) or FR (further defined herein) of the variable region. For example, the heavy chain variable region may include a single insertion residue after residue 52 of CDRH2 (i.e., residue 52a according to Kabat) and an insertion residue after residue 82 of the heavy chain FR (i.e., residues 82a, 82b, 82c according to Kabat, etc.). The Kabat residue number of a given antibody can be determined by alignment of the homologous region of the antibody sequence with a "standard" Kabat numbering sequence.

As used herein, the terms "complementarity determining region" and "CDR" refer to regions of an antibody variable domain or variable region that are hypervariable in sequence and/or form structurally defined loops. CDRs are also known as hypervariable regions. The light and heavy chain variable regions each have three CDRs. The light chain variable region contains CDR L1, CDR L2 and CDR L3. The heavy chain variable region contains CDR H1, CDR H2 and CDRH3. Each CDR may include amino acid residues from a complementarity determining region as defined by Kabat (i.e., about residues 24-34 (CDR L1), 50-56 (CDR L2) and 89-97 (CDR L3) in the light chain variable region, and about residues 31-35 (CDR H1), 50-65 (CDR H2) and 95-102 (CDRH 3) in the heavy chain variable region).

As used herein, the term "FcRn" refers to a neonatal Fc receptor that binds to the Fc region of an IgG antibody (e.g., an IgG1 antibody). An exemplary FcRn is human FcRn with UniProt ID number P55899, which is hereby incorporated by reference in its entirety. It is believed that human FcRn is responsible for maintaining the half-life of IgG by binding and transporting constitutively internalized IgG back to the cell surface for IgG recycling.

In some embodiments, the anti-FcRn antibody comprises a heavy chain or a light chain. In some embodiments, the anti-FcRN antibody comprises a heavy chain and a light chain in scFv format. In some embodiments, the heavy and light chains are linked to a peptide linker, such as a glycine/serine or glycine/alanine linker.

In some embodiments, the anti-FcRn antibody is M281. In some embodiments, the anti-FcRn antibody is nicarbazin. In some embodiments, M281 and nicarbazin comprise the same amino acid sequence. In some embodiments, M281 and nicarbazin comprise the same heavy and light chain amino acid sequences. In some embodiments, M281 and nicarbazin comprise the same variable heavy and variable light chain amino acid sequences. As used herein, "M281" and "nicarbazin" refer to the same antibody and are used interchangeably. In a preferred embodiment, the anti-FcRn antibody is M281.

In some embodiments, the anti-FcRn antibody may be M281 (nicrolimab). In some embodiments, the nicalimumab comprises or consists of: a light chain comprising or consisting of:

QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS(SEQ ID NO:1)；

and a heavy chain comprising or consisting of:

EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG(SEQ ID NO:2)。

in some embodiments, the antibody has: (a) A light chain sequence at least 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO. 1, wherein CDR L1 comprises the sequence TGTGSDVGSYNLVS (SEQ ID NO. 3), CDR L2 comprises the sequence GDSERPS (SEQ ID NO. 4), CDRL3 comprises the sequence SSYAGSGIYV (SEQ ID NO. 5); and (b) a heavy chain sequence that is at least 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO. 2, wherein CDR H1 comprises the sequence TYAMG (SEQ ID NO. 6), CDR H2 comprises the sequence SIGASGSQTRYADS (SEQ ID NO. 7), and CDR H3 comprises the sequence LAIGDSY (SEQ ID NO. 8). In some embodiments, the nicarbazin comprises or consists of a heavy chain comprising or consisting of the sequence set forth in SEQ ID NO. 2, wherein SEQ ID NO. 2 further comprises a C-terminal lysine (K). In some embodiments, SEQ ID NO. 2 contains the C-terminal lysine (K) residue at position 446. In some embodiments, the nicalimumab comprises or consists of a heavy chain comprising or consisting of a sequence lacking a C-terminal lysine (K) residue. In some embodiments, the nicarbazin comprises or consists of a heavy chain comprising or consisting of a sequence lacking the C-terminal lysine (K) at position 446.

In some embodiments, the antibody heavy chain comprises an amino acid sequence that is at least 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO. 2 with one or more amino acid substitutions, wherein the amino acid substitutions may be A23V or S30R relative to the sequence of SEQ ID NO. 2 (numbering according to Kabat). In some embodiments, the antibody light chain comprises an amino acid sequence having one or more amino acid substitutions that is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO. 1.

In some embodiments, the antibody comprises a light chain variable region comprising an amino acid sequence that is at least 95%, 97%, 99% or 100% identical to the sequence: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMI YGDSERPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVF GTGTKVTVL (SEQ ID NO: 9). In some embodiments, the light chain variable region comprises CDR L1 having the sequence TGTGSDVGSYNLVS (SEQ ID NO: 3), CDRL2 having the sequence GDSERPS (SEQ ID NO: 4), CDR L3 having the sequence SSYAGSGIYV (SEQ ID NO: 5). In some embodiments, the antibody comprises a heavy chain variable region comprising an amino acid sequence that is at least 95%, 97%, 99% or 100% identical to the sequence: EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSS (SEQ ID NO: 10). In some embodiments, the heavy chain variable region comprises CDR H1 having the sequence TYAMG (SEQ ID NO: 6), CDR H2 having the sequence SIGASGSQTRYADS (SEQ ID NO: 7) and CDRH3 having the sequence LAIGDSY (SEQ ID NO: 8).

Antibodies may also contain amino acid substitutions, additions and/or deletions outside the CDRs (i.e., in the Framework Regions (FR)). Amino acid substitutions, additions and/or deletions may be substitutions, additions and/or deletions of one or more amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8 or more). Amino acid substitutions, additions and/or deletions may be eight or less, seven or less, six or less, five or less, four or less, three or less, or two or less single amino acid substitutions, additions and/or deletions. In some embodiments, the antibody may further comprise any one or more of the following amino acid substitutions relative to the sequence of any one of SEQ ID NOs 2, 23-26 (numbered according to Kabat): a23V, S R.

In some embodiments, an antibody may include amino acid substitutions, additions, and/or deletions in the constant region (e.g., fc region) of the antibody that result in, for example, reduced effector function, e.g., reduced Complement Dependent Cytolysis (CDC), antibody dependent cell-mediated cytolysis (ADCC), and/or antibody dependent cell-mediated phagocytosis (ADCP), and/or reduced B cell killing. The constant regions are not directly involved in binding of the antibody to its target, but rather exhibit various effector functions, such as antibody involvement in antibody-dependent cytotoxicity. In some embodiments, the antibody is characterized by reduced binding (i.e., no binding) to human complement factor C1q and/or human Fc receptor on Natural Killer (NK) cells. In some embodiments, the antibody is characterized by reduced binding (i.e., no binding) to human fcyri, fcyriia, and/or fcyriiia. To alter or reduce antibody dependent effector functions, such as CDC, ADCC, ADCP and/or B cell killing, the antibody may be of the IgG class and contain one or more amino acid substitutions E233, L234, G236, D265, D270, N297, E318, K320, K322, a327, a330, P331, and/or P329 (numbering according to the EU system). In some embodiments, the antibody contains the mutation L234A/L235A or D265A/N297A. In some embodiments, the anti-FcRn antibody is non-glycosylated at position 297. The resulting non-effector antibodies show very little binding to complement or Fc receptors (i.e., complement C1q binding), indicating low CDC potential.

In some embodiments, the isolated antibody contains CDRL1 having the sequence TGTGTGSDVGSYNLVS (SEQ ID NO: 3), CDRL 2 having the sequence GDSERPS (SEQ ID NO: 4), CDRL 3 having the sequence SSYAGSGIYV (SEQ ID NO: 5), CDRH 1 having the sequence NYAMG (SEQ ID NO: 12), CDRH2 having the sequence SIGASGAQTRYADS (SEQ ID NO: 14), and CDRH3 having the sequence LAIGDSY (SEQ ID NO: 8).

In some embodiments, the isolated antibody contains CDRL1 having the sequence TGTGTGSDVGSYNLVS (SEQ ID NO: 3), CDRL 2 having the sequence GDSERPS (SEQ ID NO: 4), CDRL 3 having the sequence SSYAGSGIYV (SEQ ID NO: 5), CDRH 1 having the sequence TYAMG (SEQ ID NO: 4), CDRH2 having the sequence SIGASGGQTRYADS (SEQ ID NO: 15), and CDRH3 having the sequence LAIGDSY (SEQ ID NO: 8).

In some embodiments, the isolated antibody has a light chain and a heavy chain, wherein the light chain comprises a sequence having the sequence:

and the heavy chain comprises a sequence having the sequence:

EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV

MHEALHNHYTQKSLSLSPG(SEQ ID NO:2)。

in some embodiments, the isolated antibody has a heavy chain, wherein the heavy chain comprises a sequence having the sequence set forth in SEQ ID NO. 2, and further comprises a C-terminal lysine (K) residue. In some embodiments, SEQ ID NO. 2 contains the C-terminal lysine (K) residue at position 446.

In some embodiments, the light chain of the isolated antibody comprises a sequence having at least 90% identity to:

QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS(SEQ ID NO:1)。

in some embodiments, the heavy chain of the isolated antibody comprises a sequence having at least 90% identity to:

in some embodiments, the isolated antibody has a heavy chain, wherein the heavy chain comprises a sequence having at least 90% identity to the sequence set forth in SEQ ID NO. 2, and further comprises a C-terminal lysine (K) residue. In some embodiments, the sequence having at least 90% identity to SEQ ID NO. 2 comprises a C-terminal lysine (K) residue at position 446.

EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGSSGAQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG(SEQ ID NO:23)。

in some embodiments, the isolated antibody has a heavy chain, wherein the heavy chain comprises a sequence having at least 90% identity to the sequence set forth in SEQ ID NO. 23, and further comprises a C-terminal lysine (K) residue. In some embodiments, the sequence having at least 90% identity to SEQ ID NO. 23 comprises a C-terminal lysine (K) residue at position 446.

EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYAMGWVRQAPGKGLEWVSSIGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG(SEQ ID NO:24)。

In some embodiments, the isolated antibody has a heavy chain, wherein the heavy chain comprises a sequence having at least 90% identity to the sequence set forth in SEQ ID NO. 24, and further comprises a C-terminal lysine (K) residue. In some embodiments, the sequence having at least 90% identity to SEQ ID NO. 24 comprises a C-terminal lysine (K) residue at position 446.

EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYAMGWVRQAPGKGLEWVSSIGASGAQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG(SEQ ID NO:25)。

in some embodiments, the isolated antibody has a heavy chain, wherein the heavy chain comprises a sequence having at least 90% identity to the sequence set forth in SEQ ID NO. 25, and further comprises a C-terminal lysine (K) residue. In some embodiments, the sequence having at least 90% identity to SEQ ID NO. 25 comprises a C-terminal lysine (K) residue at position 446.

EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGGQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG(SEQ ID NO:26)。

in some embodiments, the isolated antibody has a heavy chain, wherein the heavy chain comprises a sequence having at least 90% identity to the sequence set forth in SEQ ID NO. 26, and further comprises a C-terminal lysine (K) residue. In some embodiments, the sequence having at least 90% identity to SEQ ID NO. 26 comprises a C-terminal lysine (K) residue at position 446.

In some embodiments, an isolated antibody has a light chain and a heavy chain, wherein the light chain comprises a sequence having at least 90%, 95%, 98% or 99% identity to:

and the heavy chain comprises a sequence having at least 90%, 95%, 98% or 99% identity to:

MHEALHNHYTQKSLSLSPG(SEQ ID NO:2)。

in some embodiments, the isolated antibody has a heavy chain, wherein the heavy chain comprises a sequence having at least 90%, 95%, 98% or 99% identity to the sequence set forth in SEQ ID NO. 2, and further comprises a C-terminal lysine (K) residue. In some embodiments, the sequence having at least 90%, 95%, 98% or 99% identity to SEQ ID NO. 2 comprises a C-terminal lysine (K) residue at position 446.

in some embodiments, the isolated antibody has a heavy chain, wherein the heavy chain comprises a sequence having at least 90%, 95%, 98% or 99% identity to the sequence set forth in SEQ ID NO. 23, and further comprises a C-terminal lysine (K) residue. In some embodiments, a sequence having at least 90%, 95%, 98% or 99% identity to SEQ ID NO. 23 comprises a C-terminal lysine (K) residue at position 446.

In some embodiments, an isolated antibody comprises a light chain and a heavy chain, wherein the light chain comprises a sequence having at least 90%, 95%, 98% or 99% identity to:

in some embodiments, the isolated antibody has a heavy chain, wherein the heavy chain comprises a sequence having at least 90%, 95%, 98% or 99% identity to the sequence set forth in SEQ ID NO. 24, and further comprises a C-terminal lysine (K) residue. In some embodiments, a sequence having at least 90%, 95%, 98% or 99% identity to SEQ ID NO. 24 comprises a C-terminal lysine (K) residue at position 446.

in some embodiments, the isolated antibody has a heavy chain, wherein the heavy chain comprises a sequence having at least 90%, 95%, 98% or 99% identity to the sequence set forth in SEQ ID NO. 25, and further comprises a C-terminal lysine (K) residue. In some embodiments, a sequence having at least 90%, 95%, 98% or 99% identity to SEQ ID NO. 25 comprises a C-terminal lysine (K) residue at position 446.

in some embodiments, the isolated antibody has a heavy chain, wherein the heavy chain comprises a sequence having at least 90%, 95%, 98% or 99% identity to the sequence set forth in SEQ ID NO. 26, and further comprises a C-terminal lysine (K) residue. In some embodiments, the sequence having at least 90%, 95%, 98% or 99% identity to SEQ ID NO. 26 comprises a C-terminal lysine (K) residue at position 446.

In some embodiments, the heavy chain of an isolated antibody comprises a sequence having at least 95%, 97%, 99% or 100% identity to the sequence of any one of SEQ ID NOs 2, 23-26. In some embodiments, the heavy chain of the isolated antibody comprises a sequence having at least 95%, 97%, 99% or 100% identity to the sequence of any one of SEQ ID NOS: 2, 23-26, which sequence further comprises a C-terminal lysine (K) residue at position 446 of any one of SEQ ID NOS: 2, 23-26. In other embodiments, the light chain of the isolated antibody comprises a sequence having at least 95%, 97%, 99% or 100% identity to the sequence of SEQ ID NO. 1.

In some embodiments, the heavy chain of the isolated antibody comprises a sequence having NO more than 5, 4, 3, 2, or 1 single amino acid substitutions relative to the amino acid sequence of any of SEQ ID nos. 2. In some embodiments, the heavy chain of the isolated antibody comprises a sequence having NO more than 5, 4, 3, 2, or 1 single amino acid substitutions relative to the amino acid sequence of any of SEQ ID NOs 2, and further comprises a C-terminal lysine (K) residue at position 446. In some embodiments, the light chain of the isolated antibody comprises a sequence having NO more than 5, 4, 3, 2, or 1 single amino acid substitutions relative to the sequence of SEQ ID No. 1.

In some embodiments, the isolated antibody further comprises any one or more of the following amino acid substitutions relative to the sequence of any one of SEQ ID NOs 2, 23-26: a23V, S R (numbering according to EU). In some embodiments, the isolated antibody further comprises any one or more of the following amino acid substitutions relative to the sequence of any one of SEQ ID NOs 2, 23-26: a23V, S R (numbering according to EU), and further comprises a C-terminal lysine (K) residue at position 446 of any of SEQ ID nos. 2, 23-26.

In some embodiments, the isolated antibody does not contain a C-terminal lysine at residue 446 relative to the sequence of any of SEQ ID NOs 2.

In some embodiments, the isolated antibody has a light chain and a heavy chain, wherein the light chain comprises or consists of:

and the heavy chain comprises or consists of the following sequences:

MHEALHNHYTQKSLSLSPG(SEQ ID NO:2)。

and the heavy chain comprises or consists of the following sequences:

in some embodiments, the isolated antibody has a light chain and a heavy chain, wherein the light chain comprises the following sequences:

and the heavy chain comprises or consists of the following sequences:

As used herein, the term "percent identity (%)" refers to the percentage of amino acid (or nucleic acid) residues of a candidate sequence (e.g., an anti-FcRn antibody of the present disclosure) that are identical to amino acid (or nucleic acid) residues of a reference sequence (e.g., a wild-type anti-FcRn antibody) after aligning the sequences and introducing gaps (if desired) to achieve the maximum percent identity (i.e., gaps can be introduced in one or both of the candidate sequence and the reference sequence for optimal alignment, and non-homologous sequences can be ignored for comparison purposes). Alignment for the purpose of determining percent identity can be accomplished in a variety of ways within the skill of the art, for example using publicly available computer software such as BLAST, ALIGN, or Megalign (DNASTAR) software. One skilled in the art can determine appropriate parameters for measuring the alignment, including any algorithms needed to achieve maximum alignment over the full length of the sequences to be compared. In some embodiments, the percentage of amino acid (or nucleic acid) sequence identity (which may alternatively be expressed as a percentage of amino acid (or nucleic acid) sequence identity) of a given candidate sequence and, with or relative to a given reference sequence) is calculated as follows:

100× (fraction A/B)

Wherein a is the number of amino acid (or nucleic acid) residues scored the same in the alignment of the candidate sequence and the reference sequence, and wherein B is the total number of amino acid (or nucleic acid) residues in the reference sequence. In some embodiments, wherein the length of the candidate sequence is not equal to the length of the reference sequence, the percentage of amino acid (or nucleic acid) sequence identity of the candidate sequence to the reference sequence will not be equal to the percentage of amino acid (or nucleic acid) sequence identity of the reference sequence to the candidate sequence.

In some embodiments, an alignment of the reference sequence with the candidate sequence for comparison may show that the candidate sequence exhibits 50% to 100% identity over the entire length of the candidate sequence or over selected portions of consecutive amino acid (or nucleic acid) residues of the candidate sequence. The length of the candidate sequences aligned for comparison purposes is at least 30%, such as at least 40%, such as at least 50%, 60%, 70%, 80%, 90% or 100% of the length of the reference sequence. When a position in the candidate sequence is occupied by the same amino acid (or nucleic acid) residue as the corresponding position in the reference sequence, then the molecules are identical at that position. The position may be changed by substitution, deletion or insertion. Substitutions, deletions or insertions may comprise a number of amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more). When no more than n amino acid substitutions, deletions or insertions are described, this means that the substitutions, deletions or insertions comprise, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or n amino acids. The number of substitutions, deletions or insertions may comprise a percentage (e.g., 1%, 5%, 10%, 15%, 20% or more) of the total sequence, with the number of substitutions, deletions or insertions varying by 5%, 10%, 15%, 20% or more of the amino acids in the total sequence.

In some embodiments, the Fc domain of the antibody is not fucosylated. In some embodiments of all methods described herein, the Fc domain of the antibody is not glycosylated. In some embodiments of all methods described herein, the antibody lacks effector function. In some embodiments of all methods described herein, the antibody is an IgG1 antibody.

In some embodiments, the anti-FcRn antibody is nicarbazin, RVT-1401 (HL 161), luo Zanuo Xiximab (UCB 7665), ALXN1830, ABY-039 or Egartimmod (efgartisimod). RVT-1401 (also known as HL161 BKN) is described in PCT publication number WO2020097099, luo Zanuo ximab is described in PCT publication number WO2014019727, and ezetimode (ARGX-113) is described in PCT publication number WO2015100299, each of which is hereby incorporated by reference in its entirety. In some embodiments, the anti-FcRn antibody is a biological analog of any of the anti-FcRn antibodies provided herein.

In some embodiments, the methods described herein comprise administering an anti-FcRn antibody to a pediatric subject or patient. The terms "pediatric subject" or "pediatric patient" are used interchangeably. In some embodiments, the pediatric subject is 2 years old to less than 18 years old. In some embodiments, the pediatric subject is 2 years old to less than 12 years old. In some embodiments, the pediatric subject is 12 years old to less than 18 years old. In some embodiments, the pediatric subject is a teenager defined as less than 18 years of age or 16 to 17 years of age. In some embodiments, the pediatric subject is young, defined as 12 years to 15 years of age. In some embodiments, the pediatric subject is a child, defined as 2 years to 11 years old.

Myasthenia gravis in the pediatric population is divided into three categories: 1) temporary neonatal muscle weakness, 2) juvenile myasthenia gravis (juvenile MG) and 3) congenital myasthenia gravis syndrome (CMS). Adolescent MG is an autoimmune disorder in which autoantibodies, which are structural components of the neuromuscular junction, disrupt neuromuscular transmission. In some embodiments, the methods described herein comprise administering an anti-FcRn antibody to a pediatric subject diagnosed with temporary neonatal muscle weakness. In some embodiments, the methods described herein comprise administering an anti-FcRn antibody to a pediatric subject diagnosed with juvenile myasthenia gravis (juvenile MG). In some embodiments, the methods described herein comprise administering an anti-FcRn antibody to a pediatric subject diagnosed with congenital myasthenia gravis syndrome (CMS).

In some embodiments, a method of treating pediatric myasthenia gravis in a pediatric patient in need thereof is provided. In some embodiments, the method comprises administering an initial loading dose of about 30mg/kg to about 60mg/kg of an anti-FcRn antibody, followed by a maintenance dose of about 15mg/kg to about 30mg/kg of an anti-FcRn antibody, wherein the anti-FcRn antibody comprises: heavy chains comprising HCDR1 of SEQ ID NO. 6, HCDR2 of SEQ ID NO. 7 and HCDR3 of SEQ ID NO. 8; a light chain comprising LCDR1 of SEQ ID NO. 3, LCDR2 of SEQ ID NO. 4 and LCDR3 of SEQ ID NO. 5; wherein the administration reduces serum IgG of the patient by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of baseline serum IgG, and wherein the pediatric muscle weakness is transient neonatal muscle weakness.

In some embodiments, a method of treating pediatric myasthenia gravis in a pediatric patient in need thereof is provided. In some embodiments, the method comprises administering an initial loading dose of about 30mg/kg to about 60mg/kg of an anti-FcRn antibody, followed by a maintenance dose of about 15mg/kg to about 30mg/kg of an anti-FcRn antibody, wherein the anti-FcRn antibody comprises: heavy chains comprising HCDR1 of SEQ ID NO. 6, HCDR2 of SEQ ID NO. 7 and HCDR3 of SEQ ID NO. 8; a light chain comprising LCDR1 of SEQ ID NO. 3, LCDR2 of SEQ ID NO. 4 and LCDR3 of SEQ ID NO. 5; wherein the administration reduces serum IgG of the patient by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of baseline serum IgG, and wherein the pediatric myasthenia gravis is juvenile myasthenia gravis.

In some embodiments, a method of treating pediatric myasthenia gravis in a pediatric patient in need thereof is provided. In some embodiments, the method comprises administering an initial loading dose of about 30mg/kg to about 60mg/kg of an anti-FcRn antibody, followed by a maintenance dose of about 15mg/kg to about 30mg/kg of an anti-FcRn antibody, wherein the anti-FcRn antibody comprises: heavy chains comprising HCDR1 of SEQ ID NO. 6, HCDR2 of SEQ ID NO. 7 and HCDR3 of SEQ ID NO. 8; a light chain comprising LCDR1 of SEQ ID NO. 3, LCDR2 of SEQ ID NO. 4 and LCDR3 of SEQ ID NO. 5; wherein the administration reduces serum IgG of the patient by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of baseline serum IgG, and wherein the pediatric myasthenia gravis is congenital myasthenia gravis syndrome.

In some embodiments, the antibody is administered as part of a pharmaceutical composition comprising 5mg/ml to 60mg/ml antibody. In some embodiments, the antibody is administered at an initial dose of 60 mg/kg. In some embodiments, the antibody is administered at an initial dose of 30 mg/kg. In some embodiments, the antibody is administered at an initial loading dose of 60 mg/kg. In some embodiments, the antibody is administered at an initial loading dose of 30 mg/kg. In some embodiments, the antibody is administered at a dose of about 5mg/kg to about 60mg/kg, about 5mg/kg to about 15mg/kg, about 15mg/kg to about 60mg/kg, or about 30mg/kg to about 60 mg/kg. In some embodiments, the antibody is administered at a dose of about 5mg/kg, about 15mg/kg, about 30mg/kg, about 45mg/kg, or about 60 mg/kg. In some embodiments, the antibody is administered at a dose of about 5mg/kg, 10mg/kg, 15mg/kg, 20mg/kg, 25mg/kg, 30mg/kg, 35mg/kg, 40mg/kg, 45mg/kg, 50mg/kg, 55mg/kg, or 60 mg/kg. In some embodiments, the antibody is administered in a single dose or in an initial loading dose and a maintenance dose. In some embodiments, the initial loading dose and the maintenance dose are the same dose. In some embodiments, the loading dose and the maintenance dose are not the same dose. In some embodiments, the loading dose is administered at a dose of about 5mg/kg to about 60mg/kg, about 5mg/kg to about 15mg/kg, about 15mg/kg to about 60mg/kg, or about 30mg/kg to about 60 mg/kg. In some embodiments, the loading dose is administered at a dose of 60 mg/kg. In some embodiments, the loading dose is administered at a dose of 30 mg/kg. In some embodiments, the maintenance dose is administered at a dose of about 5mg/kg to about 60mg/kg, about 5mg/kg to about 15mg/kg, about 15mg/kg to about 60mg/kg, or about 30mg/kg to about 60 mg/kg. In some embodiments, the maintenance dose is administered at a dose of about 5mg/kg, about 15mg/kg, about 30mg/kg, about 45mg/kg, or about 60 mg/kg. In some embodiments, the maintenance dose is administered at a dose of 5mg/kg, 10mg/kg, 15mg/kg, 20mg/kg, 25mg/kg, 30mg/kg, 35mg/kg, 40mg/kg, 45mg/kg, 50mg/kg, 55mg/kg, or 60 mg/kg. In some embodiments, the maintenance dose is administered at a dose of 15 mg/kg. In some embodiments, the loading dose is administered at a dose of about 30mg/kg and the maintenance dose is administered at a dose of about 15 mg/kg. In some embodiments, the loading dose is administered at a dose of 30mg/kg and the maintenance dose is administered at a dose of 15 mg/kg.

In some embodiments, the antibody is administered weekly, biweekly, or monthly. In some embodiments, the initial dose is different from a weekly or biweekly dose. In some embodiments, the dose is the same at each administration. In some embodiments, the antibody is administered at least weekly, biweekly, every 3 weeks, or every four weeks (i.e., once monthly). In some embodiments, a first infusion of antibody is administered at a loading dose of about 60mg/kg and a second infusion of antibody is administered weekly at a maintenance dose of about 15 mg/kg. In some embodiments, a first infusion of antibody is administered at a loading dose of about 30mg/kg and a second infusion of antibody is administered weekly at a maintenance dose of about 15 mg/kg. In some embodiments, the first infusion of antibody is administered at a loading dose of about 60mg/kg and the second infusion of antibody is administered at a maintenance dose of about 15mg/kg every 2 weeks. In some embodiments, the first infusion of antibody is administered at a loading dose of about 30mg/kg and the second infusion of antibody is administered at a maintenance dose of about 15mg/kg every 2 weeks. In some embodiments, the first infusion of antibody is administered at a loading dose of about 60mg/kg and the second infusion of antibody is administered every 3 weeks at a maintenance dose of about 15 mg/kg. In some embodiments, the first infusion of antibody is administered at a loading dose of about 30mg/kg and the second infusion of antibody is administered every 3 weeks at a maintenance dose of about 15 mg/kg. In some embodiments, the first infusion of antibody is administered at a loading dose of about 60mg/kg and the second infusion of antibody is administered at a maintenance dose of about 15mg/kg every 4 weeks. In some embodiments, the first infusion of antibody is administered at a loading dose of about 30mg/kg and the second infusion of antibody is administered at a maintenance dose of about 15mg/kg every 4 weeks. In some embodiments, a first infusion of antibody is administered at a loading dose of about 60mg/kg and a second infusion of antibody is administered monthly at a maintenance dose of about 15 mg/kg. In some embodiments, a first infusion of antibody is administered at a loading dose of about 30mg/kg and a second infusion of antibody is administered monthly at a maintenance dose of about 15 mg/kg.

In some embodiments, a first infusion of antibody is administered at a loading dose of about 5mg/kg to 60mg/kg, and a second infusion of antibody is administered weekly at a maintenance dose of about 5mg/kg to 60 mg/kg. In some embodiments, the first infusion of antibody is administered at a loading dose of about 5mg/kg to 60mg/kg and the second infusion of antibody is administered at a maintenance dose of about 5mg/kg to 60mg/kg every 2 weeks. In some embodiments, the first infusion of antibody is administered at a loading dose of about 5mg/kg to 60mg/kg and the second infusion of antibody is administered at a maintenance dose of about 5mg/kg to 60mg/kg every 3 weeks. In some embodiments, the first infusion of antibody is administered at a loading dose of about 5mg/kg to 60mg/kg and the second infusion of antibody is administered at a maintenance dose of about 5mg/kg to 60mg/kg every 4 weeks. In some embodiments, the first infusion of antibody is administered at a loading dose of about 5mg/kg to 60mg/kg and the second infusion of antibody is administered at a maintenance dose of about 5mg/kg to 60mg/kg monthly. In some embodiments, a first infusion of antibody is administered at a loading dose of about 5mg/kg to 30mg/kg, and a second infusion of antibody is administered weekly at a maintenance dose of about 5mg/kg to 30 mg/kg. In some embodiments, the first infusion of antibody is administered at a loading dose of about 5mg/kg to 30mg/kg and the second infusion of antibody is administered at a maintenance dose of about 5mg/kg to 30mg/kg every 2 weeks. In some embodiments, the first infusion of antibody is administered at a loading dose of about 5mg/kg to 30mg/kg and the second infusion of antibody is administered at a maintenance dose of about 5mg/kg to 30mg/kg every 3 weeks. In some embodiments, the first infusion of antibody is administered at a loading dose of about 5mg/kg to 30mg/kg and the second infusion of antibody is administered at a maintenance dose of about 5mg/kg to 30mg/kg every 4 weeks. In some embodiments, a first infusion of antibody is administered at a loading dose of about 5mg/kg to 30mg/kg and a second infusion of antibody is administered at a maintenance dose of about 5mg/kg to 30mg/kg monthly. In some embodiments, a first infusion of antibody is administered at a loading dose of about 15mg/kg to 30mg/kg, and a second infusion of antibody is administered weekly at a maintenance dose of about 15mg/kg to 30 mg/kg. In some embodiments, the first infusion of antibody is administered at a loading dose of about 15mg/kg to 30mg/kg and the second infusion of antibody is administered at a maintenance dose of about 15mg/kg to 30mg/kg every 2 weeks. In some embodiments, the first infusion of antibody is administered at a loading dose of about 15mg/kg to 30mg/kg and the second infusion of antibody is administered at a maintenance dose of about 15mg/kg to 30mg/kg every 3 weeks. In some embodiments, the first infusion of antibody is administered at a loading dose of about 15mg/kg to 30mg/kg and the second infusion of antibody is administered at a maintenance dose of about 15mg/kg to 30mg/kg every 4 weeks. In some embodiments, a first infusion of antibody is administered at a loading dose of about 15mg/kg to 30mg/kg and a second infusion of antibody is administered at a maintenance dose of about 15mg/kg to 30mg/kg monthly. In some embodiments, a first infusion of antibody is administered at a loading dose of about 60mg/kg and a second infusion of antibody is administered weekly at a maintenance dose of about 30 mg/kg. In some embodiments, the first infusion of antibody is administered at a loading dose of about 60mg/kg and the second infusion of antibody is administered at a maintenance dose of about 30mg/kg every 2 weeks. In some embodiments, the first infusion of antibody is administered at a loading dose of about 60mg/kg and the second infusion of antibody is administered at a maintenance dose of about 30mg/kg every 3 weeks. In some embodiments, the first infusion of antibody is administered at a loading dose of about 60mg/kg and the second infusion of antibody is administered at a maintenance dose of about 30mg/kg every 4 weeks. In some embodiments, a first infusion of antibody is administered at a loading dose of about 60mg/kg and a second infusion of antibody is administered monthly at a maintenance dose of about 30 mg/kg. In some embodiments, a first infusion of antibody is administered at a loading dose of about 30mg/kg and a second infusion of antibody is administered weekly at a maintenance dose of about 30 mg/kg. In some embodiments, the first infusion of antibody is administered at a loading dose of about 30mg/kg and the second infusion of antibody is administered at a maintenance dose of about 30mg/kg every 2 weeks. In some embodiments, the first infusion of antibody is administered at a loading dose of about 30mg/kg and the second infusion of antibody is administered at a maintenance dose of about 30mg/kg every 3 weeks. In some embodiments, the first infusion of antibody is administered at a loading dose of about 30mg/kg and the second infusion of antibody is administered at a maintenance dose of about 30mg/kg every 4 weeks. In some embodiments, a first infusion of antibody is administered at a loading dose of about 30mg/kg and a second infusion of antibody is administered monthly at a maintenance dose of about 30 mg/kg. In some embodiments, the additional infusion is performed at a maintenance dose of about 5mg/kg to 60 mg/kg. In some embodiments, the additional infusion is performed at a maintenance dose of about 5mg/kg to 30 mg/kg. In some embodiments, the additional infusion is performed at a maintenance dose of about 15mg/kg to 30 mg/kg. In some embodiments, the additional infusion is performed at a maintenance dose of about 15 mg/kg. In some embodiments, the additional infusion is performed at a maintenance dose of about 30 mg/kg. In some embodiments, the infusion (including the first infusion, the second infusion, and/or the additional infusion) is administered every two weeks, every 3 weeks, or every 4 weeks or monthly. In some embodiments, the method includes an initial (loading) dose followed by a maintenance dose every two weeks (e.g., once every two weeks). In some embodiments, the method comprises an initial (loading) dose followed by a maintenance dose every 3 weeks. In some embodiments, the method comprises an initial (loading) dose followed by a maintenance dose every 4 weeks. In some embodiments, the method comprises an initial (loading) dose followed by a monthly maintenance dose. In some embodiments, the initial dose is higher than the maintenance dose every two weeks. In some embodiments, the initial dose is the same as the maintenance dose every two weeks.

In some embodiments, administration of the antibody or pharmaceutical composition occurs within about 30 minutes to 90 minutes. In some embodiments, the administration occurs within about 15 minutes to 60 minutes. In some embodiments, the administration is performed within about 15 minutes to 30 minutes. In some embodiments, the administration is performed within about 15 minutes to 45 minutes. In some embodiments, the administration is performed within about 15 minutes to 90 minutes. In some embodiments, the administration occurs within about 15 minutes to about 120 minutes. In some embodiments, the administration occurs within about 15 minutes, about 30 minutes, about 45 minutes, about 60 minutes, about 90 minutes, or about 120 minutes.

In some embodiments, the composition is administered parenterally. In some embodiments, the composition is administered intravenously or subcutaneously. In some embodiments, the composition is administered intraperitoneally, intradermally, or intramuscularly. In one embodiment, the composition is administered intravenously. In one embodiment, the composition is administered subcutaneously. In some embodiments, the composition is administered using an infusion pump. In some embodiments, the composition is administered using an automatic syringe. In some embodiments, the composition is administered using a patch pump syringe. In some embodiments, the composition is administered using a wearable syringe. In some embodiments, the composition uses Sorrel ^TM And (3) pump application. In some embodiments, the composition is applied using a pumpSuch as those in U.S. patent No. 9,943,642, which is hereby incorporated by reference in its entirety.

In certain embodiments, a method of treating systemic myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is from 5mg/kg to 60mg/kg. In certain embodiments, a method of treating systemic myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is from 5mg/kg to 30mg/kg. In certain embodiments, the method of treating systemic myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is from 15mg/kg to 30mg/kg. In certain embodiments, a method of treating systemic myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 5mg/kg to 60mg/kg followed by a maintenance dose of 5mg/kg to 60mg/kg every 2 weeks. In certain embodiments, a method of treating systemic myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 5mg/kg to 30mg/kg followed by a maintenance dose of 5mg/kg to 30mg/kg every 2 weeks. In certain embodiments, a method of treating systemic myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 15mg/kg to 30mg/kg followed by a maintenance dose of 15mg/kg to 30mg/kg every 2 weeks. In certain embodiments, a method of treating systemic myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 5mg/kg to 60mg/kg followed by a maintenance dose of 5mg/kg to 60mg/kg every 4 weeks. In certain embodiments, a method of treating systemic myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 5mg/kg to 30mg/kg followed by a maintenance dose of 5mg/kg to 30mg/kg every 4 weeks. In certain embodiments, a method of treating systemic myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 15mg/kg to 30mg/kg followed by a maintenance dose of 15mg/kg to 30mg/kg every 4 weeks. In certain embodiments, the method of treating systemic myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 30mg/kg. In certain embodiments, the method of treating systemic myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 15mg/kg. In certain embodiments, a method of treating systemic myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 30mg/kg followed by a maintenance dose of 15mg/kg every 2 weeks. In certain embodiments, a method of treating systemic myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 30mg/kg followed by a maintenance dose of 30mg/kg every 4 weeks.

In certain embodiments, a method of treating transient neonatal muscle weakness in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is from 5mg/kg to 60mg/kg. In certain embodiments, a method of treating transient neonatal muscle weakness in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is from 5mg/kg to 30mg/kg. In certain embodiments, the method of treating transient neonatal muscle weakness in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is from 15mg/kg to 30mg/kg. In certain embodiments, a method of treating transient neonatal muscle weakness in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 5mg/kg to 60mg/kg followed by a maintenance dose of 5mg/kg to 60mg/kg every 2 weeks. In certain embodiments, a method of treating transient neonatal muscle weakness in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 5mg/kg to 30mg/kg followed by a maintenance dose of 5mg/kg to 30mg/kg every 2 weeks. In certain embodiments, a method of treating transient neonatal muscle weakness in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 15mg/kg to 30mg/kg followed by a maintenance dose of 15mg/kg to 30mg/kg every 2 weeks. In certain embodiments, a method of treating transient neonatal muscle weakness in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 5mg/kg to 60mg/kg followed by a maintenance dose of 5mg/kg to 60mg/kg every 4 weeks. In certain embodiments, a method of treating transient neonatal muscle weakness in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 5mg/kg to 30mg/kg followed by a maintenance dose of 5mg/kg to 30mg/kg every 4 weeks. In certain embodiments, a method of treating transient neonatal muscle weakness in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 15mg/kg to 30mg/kg followed by a maintenance dose of 15mg/kg to 30mg/kg every 4 weeks. In certain embodiments, the method of treating transient neonatal muscle weakness in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 30mg/kg. In certain embodiments, the method of treating transient neonatal muscle weakness in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 15mg/kg. In certain embodiments, a method of treating transient neonatal muscle weakness in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 30mg/kg followed by a maintenance dose of 15mg/kg every 2 weeks. In certain embodiments, a method of treating transient neonatal muscle weakness in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 30mg/kg followed by a maintenance dose of 30mg/kg every 4 weeks.

In certain embodiments, the method of treating juvenile myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering a therapeutically effective amount of nicarbazin to the pediatric subject, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 5mg/kg to 60mg/kg. In certain embodiments, the method of treating juvenile myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering a therapeutically effective amount of nicarbazin to the pediatric subject, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 5mg/kg to 30mg/kg. In certain embodiments, the method of treating juvenile myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering a therapeutically effective amount of nicarbazin to the pediatric subject, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 15mg/kg to 30mg/kg. In certain embodiments, the method of treating juvenile myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 5mg/kg to 60mg/kg followed by administration of nicarbazin at a maintenance dose of 5mg/kg to 60mg/kg every 2 weeks. In certain embodiments, the method of treating juvenile myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 5mg/kg to 30mg/kg followed by administration of nicarbazin at a maintenance dose of 5mg/kg to 30mg/kg every 2 weeks. In certain embodiments, the method of treating juvenile myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 15mg/kg to 30mg/kg followed by administration of nicarbazin at a maintenance dose of 15mg/kg to 30mg/kg every 2 weeks. In certain embodiments, the method of treating juvenile myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 5mg/kg to 60mg/kg followed by administration of nicarbazin at a maintenance dose of 5mg/kg to 60mg/kg every 4 weeks. In certain embodiments, the method of treating juvenile myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 5mg/kg to 30mg/kg followed by administration of nicarbazin at a maintenance dose of 5mg/kg to 30mg/kg every 4 weeks. In certain embodiments, the method of treating juvenile myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 15mg/kg to 30mg/kg followed by administration of nicarbazin at a maintenance dose of 15mg/kg to 30mg/kg every 4 weeks. In certain embodiments, the method of treating juvenile myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering a therapeutically effective amount of nicarbazin to the pediatric subject, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 30mg/kg. In certain embodiments, the method of treating juvenile myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering a therapeutically effective amount of nicarbazin to the pediatric subject, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 15mg/kg. In certain embodiments, a method of treating juvenile myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 30mg/kg followed by administration of nicarbazin at a maintenance dose of 15mg/kg every 2 weeks. In certain embodiments, the method of treating juvenile myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 30mg/kg followed by administration of nicarbazin at a maintenance dose of 30mg/kg every 4 weeks.

In certain embodiments, a method of treating congenital myasthenia gravis syndrome (CMS) in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 5mg/kg to 60mg/kg. In certain embodiments, a method of treating congenital myasthenia gravis syndrome (CMS) in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 5mg/kg to 30mg/kg. In certain embodiments, a method of treating congenital myasthenia gravis syndrome (CMS) in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 15mg/kg to 30mg/kg. In certain embodiments, a method of treating congenital myasthenia gravis syndrome (CMS) in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 5mg/kg to 60mg/kg followed by administration of the nicarbazin at a maintenance dose of 5mg/kg to 60mg/kg every 2 weeks. In certain embodiments, a method of treating congenital myasthenia gravis syndrome (CMS) in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 5mg/kg to 30mg/kg followed by administration of the nicarbazin at a maintenance dose of 5mg/kg to 30mg/kg every 2 weeks. In certain embodiments, a method of treating congenital myasthenia gravis syndrome (CMS) in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 15mg/kg to 30mg/kg followed by administration of the nicarbazin at a maintenance dose of 15mg/kg to 30mg/kg every 2 weeks. In certain embodiments, a method of treating congenital myasthenia gravis syndrome (CMS) in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 5mg/kg to 60mg/kg followed by administration of the nicarbazin at a maintenance dose of 5mg/kg to 60mg/kg every 4 weeks. In certain embodiments, a method of treating congenital myasthenia gravis syndrome (CMS) in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 5mg/kg to 30mg/kg followed by administration of the nicarbazin at a maintenance dose of 5mg/kg to 30mg/kg every 4 weeks. In certain embodiments, a method of treating congenital myasthenia gravis syndrome (CMS) in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject, wherein the nicarbazin is administered at a loading dose of 15mg/kg to 30mg/kg followed by administration of the nicarbazin at a maintenance dose of 15mg/kg to 30mg/kg every 4 weeks. In certain embodiments, the method of treating congenital myasthenia gravis syndrome (CMS) in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 30mg/kg. In certain embodiments, the method of treating congenital myasthenia gravis syndrome (CMS) in a pediatric subject in need thereof comprises intravenously administering to the pediatric subject a therapeutically effective amount of nicarbazin, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 15mg/kg. In certain embodiments, a method of treating congenital myasthenia gravis syndrome (CMS) in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 30mg/kg followed by administration of nicarbazin at a maintenance dose of 15mg/kg every 2 weeks. In certain embodiments, a method of treating congenital myasthenia gravis syndrome (CMS) in a pediatric subject in need thereof comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 30mg/kg followed by administration of nicarbazin at a maintenance dose of 30mg/kg every 4 weeks.

In certain embodiments, the method of treating transient muscle weakness in a pediatric subject, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in need thereof comprises intravenously administering a therapeutically effective amount of nicarbazin to the pediatric subject, wherein the therapeutically effective amount of nicarbazin Li Shan is 5mg/kg to 60mg/kg. In certain embodiments, the method of treating transient muscle weakness in a pediatric subject, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in need thereof comprises intravenously administering a therapeutically effective amount of nicarbazin to the pediatric subject, wherein the therapeutically effective amount of nicarbazin Li Shan is 5mg/kg to 30mg/kg. In certain embodiments, the method of treating transient muscle weakness in a pediatric subject, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in need thereof comprises intravenously administering a therapeutically effective amount of nicarbazin to the pediatric subject, wherein the therapeutically effective amount of nicarbazin Li Shan is 15mg/kg to 30mg/kg. In certain embodiments, the method of treating transient muscle weakness in a pediatric subject, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in need thereof, comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 5mg/kg to 60mg/kg followed by administration of nicarbazin at a maintenance dose of 5mg/kg to 60mg/kg every 2 weeks. In certain embodiments, the method of treating transient muscle weakness in a pediatric subject, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in need thereof, comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 5mg/kg to 30mg/kg followed by administration of nicarbazin at a maintenance dose of 5mg/kg to 30mg/kg every 2 weeks. In certain embodiments, the method of treating transient muscle weakness in a pediatric subject, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in need thereof, comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 15mg/kg to 30mg/kg followed by administration of nicarbazin at a maintenance dose of 15mg/kg to 30mg/kg every 2 weeks. In certain embodiments, the method of treating transient muscle weakness in a pediatric subject, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in need thereof, comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 5mg/kg to 60mg/kg followed by administration of nicarbazin at a maintenance dose of 5mg/kg to 60mg/kg every 4 weeks. In certain embodiments, the method of treating transient muscle weakness in a pediatric subject, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in need thereof, comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 5mg/kg to 30mg/kg followed by administration of nicarbazin at a maintenance dose of 5mg/kg to 30mg/kg every 4 weeks. In certain embodiments, the method of treating transient muscle weakness in a pediatric subject, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in need thereof, comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 15mg/kg to 30mg/kg followed by administration of nicarbazin at a maintenance dose of 15mg/kg to 30mg/kg every 4 weeks. In certain embodiments, the method of treating transient muscle weakness in a pediatric subject, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in need thereof comprises intravenously administering a therapeutically effective amount of nicarbazin to the pediatric subject, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 30mg/kg. In certain embodiments, the method of treating transient muscle weakness in a pediatric subject, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in need thereof comprises intravenously administering a therapeutically effective amount of nicarbazin to the pediatric subject, wherein the therapeutically effective amount of nicarbazin Li Shan antibody is 15mg/kg. In certain embodiments, the method of treating transient muscle weakness in a pediatric subject, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in need thereof, comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 30mg/kg followed by administration of nicarbazin at a maintenance dose of 15mg/kg every 2 weeks. In certain embodiments, the method of treating transient muscle weakness in a pediatric subject, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in need thereof, comprises intravenously administering nicarbazin to the pediatric subject at a loading dose of 30mg/kg followed by administration of nicarbazin at a maintenance dose of 30mg/kg every 4 weeks.

In some embodiments, the pharmaceutical composition comprises one or more of sodium phosphate, sodium chloride, trehalose, or polysorbate.

As used herein, the term "pharmaceutical composition" refers to a medical or pharmaceutical formulation containing an active ingredient together with one or more excipients and diluents to enable the active ingredient to be suitable for the method of administration. The pharmaceutical compositions of the present disclosure comprise a pharmaceutically acceptable component compatible with anti-FcRn antibodies. The pharmaceutical composition may be in aqueous form for intravenous or subcutaneous administration or in tablet or capsule form for oral administration. In some embodiments, the composition is suitable for intravenous administration. In some embodiments, the composition is suitable for subcutaneous administration.

In some embodiments, the pharmaceutical compositions of the invention containing an anti-FcRn antibody as a therapeutic protein may be formulated for intravenous administration, parenteral administration, subcutaneous administration, intramuscular administration, intra-arterial administration, intrathecal administration, or intraperitoneal administration. In some embodiments, the pharmaceutical composition may also be formulated for oral, nasal, spray, aerosol rectal or vaginal administration or by oral, nasal, spray, aerosol rectal or vaginal administration. For injectable formulations, various effective pharmaceutical carriers are known in the art.

As used herein, the term "pharmaceutically acceptable carrier" refers to an excipient or diluent in a pharmaceutical composition. The pharmaceutically acceptable carrier must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. In the present disclosure, a pharmaceutically acceptable carrier must provide sufficient drug stability to the Fc construct. The nature of the carrier will vary depending on the mode of administration. For example, for intravenous administration, aqueous solution carriers are typically used; for oral administration, solid carriers are preferred.

As used herein, the term "therapeutically effective amount" refers to an amount, e.g., a pharmaceutical dose, effective to induce a desired biological effect in a pediatric subject or patient or to treat a patient suffering from a disorder or condition described herein. It is also understood herein that a "therapeutically effective amount" can be construed as an amount that imparts the desired therapeutic effect, either alone or in combination with other therapeutic agents, at one dose or at any dose or route.

As used herein, the term "no more than" refers to an amount less than or equal to. This may be an integer quantity. For example, no more than two substitutions may refer to 0, 1, or 2 substitutions.

As used herein, the term "treatment" or "treatment" refers to reducing, reducing the risk of, or reducing the side effects of a particular disease or condition. The reduction, risk reduction, or side effect reduction is relative to a pediatric subject that is not receiving treatment, e.g., a control, baseline, or known control level or measurement.

Thus, in some embodiments, methods of treating myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in a pediatric subject are provided. In some embodiments, the myasthenia gravis is systemic myasthenia gravis. In some embodiments, the myasthenia gravis is transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof. In some embodiments, the myasthenia gravis is temporary myasthenia gravis. In some embodiments, the myasthenia gravis is juvenile myasthenia gravis. In some embodiments, the myasthenia gravis is congenital myasthenia gravis syndrome (CMS). In some embodiments, the pediatric subject is a pediatric subject having a suboptimal response to a stabilization therapy of gMG, transient neonatal muscle weakness, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof. In some embodiments, the stabilization therapy of gMG, transient neonatal muscle weakness, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof comprises: acetylcholinesterase inhibitors, glucocorticoids and immunosuppressants. In some embodiments, the immunosuppressant is selected from the group consisting of: azathioprine, mycophenolate mofetil/mycophenolic acid, methotrexate, cyclosporine, tacrolimus and cyclophosphamide. In some embodiments, the method comprises administering to the pediatric subject a pharmaceutical composition comprising administering an anti-FcRn antibody. In some embodiments, the anti-FcRn antibody is nicarbazin, RVT-1401 (HL 161), luo Zanuo ximab (UCB 7665), ALXN1830, ABY-039, or ezetimibe. In some embodiments, the antibody is nicarbazin. In some embodiments, an anti-FcRn antibody is as provided herein.

In some embodiments, a pediatric subject treated for myasthenia gravis exhibits an improvement in one or more of the following assays, scores, or criteria that may be used to evaluate an improvement or condition in a pediatric subject with myasthenia gravis. In some embodiments, the myasthenia gravis is transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof. In some embodiments, the myasthenia gravis is temporary myasthenia gravis. In some embodiments, the myasthenia gravis is juvenile myasthenia gravis. In some embodiments, the myasthenia gravis is congenital myasthenia gravis syndrome (CMS). In some embodiments, the pediatric subject exhibits improvement in one or more of the following: myasthenia gravis-daily life activity (MG-ADL) score, quantitative Myasthenia Gravis (QMG) score, european young life quality 5-dimensional (EQ-5D-Y) tool, myasthenia gravis quality of life (MG-QoL 15 r) score, nerve quality of life (Neuro-QoL) fatigue score, pediatric quality of life questionnaire (PedsQL), EQ-5D-5L score, EQ-5D-5Y score, american Myasthenia Gravis Foundation (MGFA) scale, patient overall severity impression (PGI-S) score, and patient overall change impression (PGI-C) score.

In some embodiments, a pediatric subject receiving treatment for myasthenia gravis, or moderate to severe active myasthenia gravis, or transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof has or exhibits a decrease in one or more immunoglobulin isotypes or total IgG. In some embodiments, the subject receiving the myasthenia gravis treatment has or exhibits a decrease in one or more immunoglobulin isotypes or total IgG. In some embodiments, the subject receiving treatment for myasthenia gravis or moderate to severe active myasthenia gravis has or exhibits a decrease in one or more immunoglobulin isotypes or total IgG. In some embodiments, the subject receiving treatment for juvenile myasthenia gravis has or exhibits a decrease in one or more immunoglobulin isotypes or total IgG. In some embodiments, the subject receiving treatment for transient neonatal muscle weakness has or exhibits a decrease in one or more immunoglobulin isotypes or total IgG. In some embodiments, a subject receiving treatment for congenital myasthenia gravis syndrome (CMS) has or exhibits a decrease in one or more immunoglobulin isotypes or total IgG. In some embodiments, the reduction is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, or 90%. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of baseline serum IgG. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG in the patient by at least 90% of baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG in the patient by at least 80% of baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG in the patient by at least 70% of baseline. In some embodiments, the isotype of the reduced immunoglobulin is IgG1, igG2, igG3, igG4, or any combination thereof. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG1 by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of baseline serum IgG 1. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG1 in the patient by at least 90% of baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG1 in the patient by at least 80% of baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG1 in the patient by at least 70% of baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG2 by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of baseline serum IgG 2. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG2 in the patient by at least 90% of baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG2 in the patient by at least 80% of baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG2 in the patient by at least 70% of baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG3 by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of baseline serum IgG 3. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG3 in the patient by at least 90% of baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG3 in the patient by at least 80% of baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG3 in the patient by at least 70% of baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG4 by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of baseline serum IgG 4. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG4 in the patient by at least 90% of baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG4 in the patient by at least 80% of baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum IgG4 in the patient by at least 70% of baseline.

In some embodiments, a pediatric subject receiving treatment for myasthenia gravis has or exhibits reduced autoantibodies. In some embodiments, the subject receiving the myasthenia gravis treatment has or exhibits reduced autoantibodies. In some embodiments, the subject receiving treatment for transient neonatal muscle weakness has or exhibits a reduction in autoantibodies. In some embodiments, the subject receiving treatment for juvenile myasthenia gravis has or exhibits reduced autoantibodies. In some embodiments, the subject receiving treatment for congenital myasthenia gravis syndrome (CMS) has or exhibits a decrease in autoantibodies. In some embodiments, the reduction is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%. In some embodiments, the reduced autoantibody is selected from the group consisting of: anti-acetylcholine receptor (AChR), anti-muscle-specific kinase (MuSK), anti-low density lipoprotein receptor-related protein 4 (LRP 4), anti-human collectin, anti-actin, anti-kv 1.4, anti-ranitidine receptor, anti-collagen Q, and anti-actin. In some embodiments, the autoantibody is an anti-AChR or anti-MuSK antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-AChR antibody by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 50%, or at least 25% of the baseline anti-AChR antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-AChR antibody by at least 95% of the baseline anti-AChR antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-AChR antibody by at least 90% of the baseline anti-AChR antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-AChR antibody by at least 85% of the baseline anti-AChR antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-AChR antibody by at least 80% of the baseline anti-AChR antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-AChR antibody by at least 75% of the baseline anti-AChR antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-AChR antibody by at least 50% of the baseline anti-AChR antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-AChR antibody by at least 25% of the baseline anti-AChR antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-MuSK antibody by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 50%, or at least 25% of the baseline anti-MuSK antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-MuSK antibody by at least 95% of the baseline anti-MuSK antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-MuSK antibody by at least 90% of the baseline anti-MuSK antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-MuSK antibody by at least 85% of the baseline anti-MuSK antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-MuSK antibody by at least 80% of the baseline anti-MuSK antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-MuSK antibody by at least 75% of the baseline anti-MuSK antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-MuSK antibody by at least 50% of the baseline anti-MuSK antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-MuSK antibody by at least 25% of the baseline anti-MuSK antibody. In some embodiments, administration of the anti-FcRn antibody reduces the anti-AChR antibody by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 50%, or at least 25% of the baseline anti-AChR antibody; and reducing the anti-MuSK antibody by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 50%, or at least 25% of the baseline anti-MuSK antibody.

In some embodiments, administration of the anti-FcRn antibody reduces serum albumin by at most 18%, at most 16%, at most 14%, at most 12%, at most 10%, at most 8%, at most 6%, at most 4%, or at most 2% of the serum albumin baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum albumin by up to 18% of the serum albumin baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum albumin by up to 16% of the serum albumin baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum albumin by up to 14% of the serum albumin baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum albumin by up to 12% of the serum albumin baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum albumin by up to 10% of the serum albumin baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum albumin by up to 8% of the serum albumin baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum albumin by up to 6% of the serum albumin baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum albumin by up to 4% of the serum albumin baseline. In some embodiments, administration of the anti-FcRn antibody reduces serum albumin by up to 2% of the serum albumin baseline.

In some embodiments, the pediatric subject is treated with an additional therapeutic agent in addition to M281. In some embodiments, the additional therapeutic agent is an acetylcholinesterase inhibitor, pyridostigmine (pyristigmine), pyridostigmine bromide (mestimine), neostigmine (neostigmine), prednisone (prednisone), azathioprine (azathioprine) (Immuran), mycophenolate (mycophenylate mofetil) (CellCept), tacrolimus (tacrolimus) (Prograf), methotrexate (methotreate), cyclosporine (cycloporine) (sandimun, neoral), and cyclophosphamide (cyclophosphamide) (Cytoxan), eculizumab (Soliris), IVIg, or any combination thereof. In some embodiments, the additional therapeutic agent is administered simultaneously or sequentially (before or after) with M281.

In some embodiments, the method comprises administering to the pediatric subject a pharmaceutical composition comprising administering an anti-FcRn antibody. In some embodiments, the anti-FcRn antibody is nicarbazin, RVT-1401 (HL 161), luo Zanuo ximab (UCB 7665), ALXN1830, ABY-039, or ezetimibe. In some embodiments, the antibody is nicarbazin. In some embodiments, an anti-FcRn antibody is as provided herein. In some embodiments, the pediatric subject has or is suspected of having myasthenia gravis. In a preferred embodiment, the anti-FcRn antibody is nicarbazin.

In some embodiments, administration of an anti-FcRn antibody to a pediatric subject with myasthenia gravis treats or ameliorates ocular myasthenia, eyelid ptosis, masticatory difficulties, dysphagia, dysarthria, hypophonia, dyspnea, inability to keep the mouth closed, sadness or somnolence, difficulty maintaining the head upright, compound vision, dysarthria, dysphagia, facial expression changes, shortness of breath, arm weakness, hand weakness, finger weakness, leg weakness, neck weakness.

In some embodiments, the treatment of myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof comprises a clinical marker to improve MG progression. These markers include the MG daily life activity curve (MG-ADL) and the Quantitative (QMG) score for the severity of myasthenia gravis. In certain embodiments, MG-ADL is the primary goal of measuring improvement in MG.

MG-ADL is an 8-point questionnaire that focuses on the functional manifestations of symptoms and Activities of Daily Living (ADL) associated with MG pediatric subjects. The 8 items of MG-ADL were derived from the symptom-based component of the original 13 QMG to evaluate disability secondary to ocular (2), bulbar (3), respiratory (1), and gross motor or limb (2) lesions associated with the effects from MG. In the functional status tool, each reaction is rated from 0 (normal) to 3 (most severe). The total MG-ADL score ranged from 0 to 24. Clinically significant improvements in MG-ADL in patients would be 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 and 24 weeks post-treatment scores reduced by 2 or more.

In some embodiments, pediatric patients treated by the methods provided herein experience a change in the myasthenia gravis daily life activity (MG-ADL) score over time or from baseline after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment. In some embodiments, the change in MG-ADL score from baseline is greater than or equal to 2 points of the MG-ADL scale.

Current QMG scoring systems consist of 13 items: eye (2), face (1), medulla oblongata (2), gross movement (6), axial (1), and respiration (1); each scale is 0 to 3, with 3 being the most severe. The total QMG score ranges from 0 to 39. The QMG scoring system is considered an objective assessment of MG treatment and is based on quantitative testing of the whistle muscle group. Higher scores indicate greater weakness. QMG is preferably administered by trained qualified health care professionals (e.g., physicians, physician assistants, caregivers, nurses). QMG will preferably be administered to a given pediatric subject by the same healthcare professional throughout the study, if possible, and will preferably be performed at about the same time throughout the study.

In some embodiments, pediatric patients treated by the methods provided herein experience a change in QMG scores from baseline after 22 weeks, 23 weeks, and 24 weeks of treatment. In some embodiments, pediatric patients treated by the methods provided herein experience a change in QMG scores from baseline over time after administration of the last dose. In some embodiments, the change from baseline is a decrease in QMG score of the patient over time of at least 2, 3, 4, 5, 6, 7, or greater than or equal to 8 points after 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment or after administration of the last dose. In some embodiments, the change from baseline is a decrease in QMG score of the patient over time after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment or after administration of the last dose of at least 2 minutes. In some embodiments, the change from baseline is a decrease in QMG score of the patient over time of at least 3 minutes after treatment 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks or after administration of the last dose. In some embodiments, the change from baseline is a decrease in QMG score of the patient over time after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment or after administration of the last dose of at least 4 points over time. In some embodiments, the change from baseline is a decrease in QMG score of the patient over time after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment or after administration of the last dose of at least 5 minutes. In some embodiments, the change from baseline is a decrease in QMG score of the patient over time after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment or after administration of the last dose of at least 6 minutes. In some embodiments, the change from baseline is a decrease in QMG score of the patient over time after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment or after administration of the last dose of at least 7 points over time. In some embodiments, the change from baseline is a decrease in QMG score of the patient over time of greater than or equal to 8 points after treatment 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks or after administration of the last dose.

The 15 myasthenia gravis quality of life scale (MG-QoL 15) is a health-related quality of life assessment tool specific to subjects with MG. MG-QoL15 is preferably designed to provide information about the subject's perception of injury and disability and the extent to which the disease manifestation is tolerated, and is easy to administer and interpret. MG-QoL15 is achieved by the subject. The total score ranges from 0 to 60, and a higher score indicates a greater degree of MG-related dysfunction and dissatisfaction therewith. MG-QoL15 is preferably used to assess subject limitations associated with MG. Each of the 15 projects was rated by the subject in a 3-component table based on the recall period of "the last few weeks", with a highest score of 30. A higher score indicates more restriction.

In some embodiments, pediatric patients treated by the methods provided herein experience a change in MG-QoL15 score from baseline over time after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment or after administration of the last dose. In some embodiments, pediatric patients treated by the methods provided herein experience a change in MG-QoL15 score from baseline over time after administration of the last dose. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

The U.S. myasthenia gravis foundation clinical classification (MGFA) can be used to assess MG severity in a subject. The system includes severity of disease from class I (eye muscle weakness alone) to class V (intubation of the subject) of class 5. Classes II to IV are further divided into 2 subclasses according to the predominantly affected muscle groups. The MGFA is preferably administered by trained qualified health care professionals (e.g., physicians, physician assistants, caregivers, nurses) and, if possible, is preferably assessed by the same person for a given subject throughout the study.

In some embodiments, pediatric patients treated by the methods provided herein undergo a transition in MGFA classification after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment. In some embodiments, a patient treated by the methods provided herein undergoes a transition in MGFA classification over time after administration of the last dose. In some embodiments, the transition is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, or 80%.

In some embodiments, pediatric patients treated by the methods provided herein experience a change in the quality of life (Neuro-QoL-fatigue) of the neurological disorder. Neuro-QoL-fatigue is a reliable and effective short 19 fatigue survey that is filled out by subjects on all projects. Higher scores indicate that MG has greater impact on heavier fatigue and activity. Clinically significant improvement in the Neuro-QoL-fatigue score of a patient reflects a decrease in score over time following administration of the last dose.

In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline on the Neuro-QoL-fatigue scale over 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks after administration of the last dose or over time. In some embodiments, a patient treated by the methods provided herein experiences a change from baseline over time after administration of the last dose on the Neuro-QoL-fatigue scale. In some embodiments, a change from baseline on Neuro-QoL-fatigue indicates improvement. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, pediatric patients treated by the methods provided herein experience a change in the EuroQol 5-dimensional 5-level quality of life questionnaire (5Q-5D-5L). EQ-5D-5L is a standardized measure of health status developed by the EuroQol group to provide a simple, universal health measure for clinical and economic evaluation. EQ-5D-5L as a measure of quality of life associated with health, health is defined in terms of 5 dimensions: activity, self-care, daily activity, pain/discomfort, anxiety/depression. Each dimension has 3 sequential severity levels: "no problem" (1), "some problems" (2), "serious problems" (3). The overall health status is defined as a 5-digit number. The health status defined by the 5-dimensional classification may be converted into a corresponding index score quantifying the health status, where-0.594 represents a "serious problem" and 1 represents "no problem".

In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline on the EQ-5D-5L scale. In some embodiments, a change from baseline on the EQ-5D-5L scale indicates improvement. In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline on the EQ-5D-5L scale over 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks after administration of the last dose or over time. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline on the EQ-5D-5Y scale. EQ-5D-Y is a standardized child-friendly instrument, designed primarily for self-completion by children and adolescents, or proxy versions completed by caregivers of children, for use as a measure of health status. The EQ-5D-Y descriptive system includes the following 5 dimensions: mobility; care for oneself (washing and dressing); daily activities; pain or discomfort; and worry or unpleasant. Each of the 5 dimensions is divided into 3 perceived problem classes (class 1 indicates no problems, class 2 indicates some problems, and class 3 indicates many problems) (EuroQol 2021;EuroQol 2019). The participant selects an answer for each of the 5 dimensions, considering the answer that best fits his or her "today's" health condition. The descriptive system may be represented as a state of health. The time taken to complete the questionnaire varies with age, health status, and environment, but may be about 1 minute.

In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline on the EQ-5D-5Y scale. In some embodiments, a change from baseline on the EQ-5D-5Y scale indicates improvement. In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline on the EQ-5D-5Y scale over 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks after administration of the last dose or over time. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, pediatric patients treated by the methods provided herein experience a change in the patient's global impression level (PGI-C). PGI-C is a patient grading assessment of treatment response on the 7-point Likertscale scale.

In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline on the PGI-C scale. In some embodiments, a change from baseline on the PGI-C scale indicates improvement. In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline on the PGI-C scale over 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks after administration or over time after administration of the last dose. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, pediatric patients treated by the methods provided herein experience a change in the patient' S overall severity impression scale (PGI-S). Patient overall severity impression (PGI-S) is an overall index (single state scale) that can be used to assess the severity of a particular condition. This is a simple, straightforward, easy to use gauge that is intuitively understandable by the clinician. PGI-S is a single problem that requires patients to assess their urinary tract pathology on a scale of 1 (normal) to 4 (severe).

In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline on the PGI-S scale. In some embodiments, a change from baseline on the PGI-S scale indicates improvement. In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline on the PGI-S scale over 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks after administration or over time after administration of the last dose. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, patients treated by the methods provided herein experience a change in the Columbia suicide severity rating scale (Columbia-Suicide Severity Rating Scale; C-SSRS). The C-SSRS is used to scale the extent of suicidal ideation of a patient ranging from "no suicidal ideation" to "active suicidal ideation with specific plan and intent". (Posner 2011)

In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline on the C-SSRS scale. In some embodiments, a change from baseline on the C-SSRS scale indicates improvement. In some embodiments, pediatric patients treated by the methods provided herein undergo a change from baseline on the C-SSRS scale over 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks after administration or over time after administration of the last dose. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, the patient treated by the methods provided herein experiences a change in the pediatric quality of life scale (PedsQL). The PedsQL measurement model is a modular method of measuring the health-related quality of life (HRQOL) of healthy children and adolescents and children suffering from acute and chronic health conditions. The PedsQL measurement model seamlessly integrates a generic core scale and disease-specific modules into one measurement system. The 23-item PedsQL universal core scale is designed to measure the core dimensions of health as well as role (school) functions as depicted by the world health organization. The PedsQL can be done by children and young adults, and the versions can be used for children and young adults between 5 years and 7 years, between 8 years and 12 years, and between 13 years and 18 years. The parental rating version may be used for children between 2 years old and 4 years old, between 5 years old and 7 years old, between 8 years old and 12 years old, and between 13 years old and 18 years old. The petsql list takes approximately five minutes to complete and can be self-administered by parents, children 8 to 18 years old, and young adults after introduction by trained administrators. For younger children and as an alternative to special cases, the clinician can manage the list as long as the instruction and all items are read verbatim to the child or young adult. Items on the PedsQL general core scale are back scored and converted to a 0-100 scale. A higher score indicates a better health-related quality of life: 0 ("never") =100; 1 ("almost never") =75; 2 ("sometimes") =50; 3 ("frequent") =25; and 4 ("almost always") =0. Version used: teenagers of children aged 13-18 report the acute version; parents reporting acute versions for children 8-12 years old; parents of young children between 5 and 7 years old report the acute version and parents of young children between 2 and 4 years old report the acute version.

In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline on the PedsQL scale. In some embodiments, a change from baseline on the PedsQL scale indicates improvement. In some embodiments, pediatric patients treated by the methods provided herein undergo a change from baseline on the PedsQL scale over 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks after administration of the last dose or over time. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

As provided herein, in some embodiments, a pharmaceutical composition comprising an anti-FcRn antibody is provided. In some embodiments, a pharmaceutical composition comprising an anti-FcRn antibody for administration to a pediatric patient suffering from myasthenia gravis is provided, wherein the anti-FcRn antibody is administered to the patient in a therapeutically effective amount of about 1mg/kg to about 100mg/kg or about 5mg/kg to about 60mg/kg every 2 weeks. In some embodiments, the myasthenia gravis is systemic myasthenia gravis. In some embodiments, the myasthenia gravis is transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof. In some embodiments, the myasthenia gravis is temporary myasthenia gravis. In some embodiments, the myasthenia gravis is juvenile myasthenia gravis. In some embodiments, the myasthenia gravis is congenital myasthenia gravis syndrome (CMS). In some embodiments, the pediatric subject is a subject having a suboptimal response to the stabilization therapy of gMG. In some embodiments, the stabilization therapy of gMG comprises: acetylcholinesterase inhibitors, glucocorticoids and immunosuppressants. In some embodiments, the immunosuppressant is selected from the group consisting of: azathioprine, mycophenolate mofetil/mycophenolic acid, methotrexate, cyclosporine, tacrolimus and cyclophosphamide. In some embodiments, the method comprises administering to the pediatric subject a pharmaceutical composition comprising administering an anti-FcRn antibody. In some embodiments, the anti-FcRn antibody is nicarbazin, RVT-1401 (HL 161), luo Zanuo ximab (UCB 7665), ALXN1830, ABY-039, or ezetimibe. In some embodiments, the anti-FcRn antibody is nicarbazin.

In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of an anti-FcRn antibody. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of an anti-FcRn antibody. In a preferred embodiment, the anti-FcRn antibody is preferably a nica Li Shan antibody. In some embodiments, the therapeutically effective amount is about 1mg/kg to about 100mg/kg, about 5mg/kg to about 60mg/kg, about 5mg/kg to about 15mg/kg, about 15mg/kg to about 60mg/kg, about 15mg/kg to about 30mg/kg, or about 30mg/kg to about 60mg/kg of the anti-FcRn antibody. In some embodiments, the therapeutically effective amount is about 1mg/kg, about 5mg/kg, about 10mg/kg, about 15mg/kg, about 20mg/kg, about 25mg/kg, about 30mg/kg, about 35mg/kg, about 40mg/kg, about 45mg/kg, about 50mg/kg, about 55mg/kg, or about 60mg/kg. In some embodiments, the therapeutically effective amount is 30mg/kg. In some embodiments, the therapeutically effective amount is 15mg/kg.

In some embodiments, the pharmaceutical composition is administered weekly, biweekly, or monthly. In some embodiments, the pharmaceutical composition is administered to the subject as an initial loading dose and a maintenance dose, and comprises: an initial loading dose comprising an anti-FcRn antibody at a dose of about 1mg/kg to about 100mg/kg, about 5mg/kg to about 60mg/kg, about 5mg/kg to about 15mg/kg, about 15mg/kg to about 60mg/kg, about 15mg/kg to about 30mg/kg, or about 30mg/kg to about 60mg/kg; and administering a maintenance dose comprising an anti-FcRn antibody to the subject at a dose of about 5mg/kg to about 45mg/kg, about 5mg/kg to about 15mg/kg, about 15mg/kg to about 45mg/kg, or about 30mg/kg to about 45 mg/kg. In some embodiments, the pharmaceutical composition is administered to the subject as an initial loading dose and a maintenance dose, and comprises: an initial loading dose comprising an anti-FcRn antibody at a dose of 30 mg/kg; and administering to the subject a maintenance dose comprising anti-FcRn antibody at a dose of 15mg/kg. In a preferred embodiment, the anti-FcRn antibody is preferably a nica Li Shan antibody.

In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis, transient neomyasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in the patient exhibiting an improvement in MG-ADL score, QMG score, MG-QoL15r score, neuro-QoL-fatigue score, EQ-5D-5L score, EQ-5D-5Y score, MGFA scale, PGI-C score, PGI-S score, and PedsQL score.

In some embodiments, the pharmaceutical composition is administered to a pediatric patient to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, treat or ameliorate myasthenia gravis, eyelid sagging, difficult chewing, dysphagia, dysarthria, dyspnea, inability to hold the mouth closed, sadness or somnolence, difficulty in maintaining the head upright, double vision, dysarthria, dysphagia, facial expression changes, shortness of breath, arm weakness, hand weakness, finger weakness, leg weakness, neck weakness.

In some embodiments, administration of the pharmaceutical composition to a pediatric patient displays a reduction in one or more immunoglobulin isotypes or total IgG in the patient. In some embodiments, the isotype is IgG1, igG2, igG3, igG4, igA, igM, or IgE. In some embodiments, the reduction is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, or 80%. In some embodiments, the isotype of the reduced immunoglobulin is IgG1, igG2, igG3, igG4, igA, igM, or IgE, or any combination thereof.

In some embodiments, administration of the pharmaceutical composition to a pediatric patient displays a reduction in autoantibodies in the patient. In some embodiments, the autoantibody is selected from the group consisting of: anti-acetylcholine receptor (AChR), anti-muscle-specific kinase (MuSK), anti-low density lipoprotein receptor-related protein 4 (LRP 4), anti-human collectin, anti-actin, anti-kv 1.4, anti-ranitidine receptor, anti-collagen Q, and anti-actin. In some embodiments, the reduction is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, the pharmaceutical composition is administered with an additional therapeutic agent in addition to the nicarbazin Li Shan antibody. In some embodiments, the additional therapeutic agent is an acetylcholinesterase inhibitor, pyridostigmine bromide (mestin), neostigmine, prednisone, azathioprine (immura), mycophenolate (CellCept), tacrolimus (Prograf), methotrexate, cyclosporine (sandimhune, neoral), and cyclophosphamide (Cytoxan, neosar), rituximab (Rituxan), eculizumab (Soliris), IVIg, or any combination thereof. In some embodiments, the additional therapeutic agent is administered simultaneously or sequentially (before or after) with the nicarbazin antibody.

In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in the pediatric patient exhibiting a change in MG-ADL score from baseline. In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis results in a change in MG-ADL score from baseline of greater than or equal to 2 points on the MG-ADL scale. In some embodiments, administration of the pharmaceutical composition to a pediatric patient results in an improvement in the patient as measured by ACR scores over time for 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks after administration of the first dose of the pharmaceutical composition to the pediatric patient.

In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in the patient exhibiting a change in QMG score from baseline over time after treatment 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks or after administration of the last dose. In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis results in the patient exhibiting a change in QMG score from baseline over time after administration of the last dose. In some embodiments, the change from baseline is a decrease in QMG score of the patient over time of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks after treatment or after administration of the last dose of the pharmaceutical composition, of greater than or equal to 8 minutes. In some embodiments, the change from baseline is at least a 2-fold decrease in QMG score of the patient after treatment 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks or after administration of the last dose of the pharmaceutical composition over time. In some embodiments, the change from baseline is at least a 3-point decrease in QMG score of the patient over time after treatment 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks or after administration of the last dose of the pharmaceutical composition. In some embodiments, the change from baseline is a decrease in QMG score of the patient over time after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment or after administration of the last dose of the pharmaceutical composition of at least 4 points over time. In some embodiments, the change from baseline is a decrease in QMG score of the patient over time after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment or after administration of the last dose of the pharmaceutical composition of at least 5 minutes. In some embodiments, the change from baseline is a decrease in QMG score of the patient over time after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment or after administration of the last dose of the pharmaceutical composition of at least 6 points over time. In some embodiments, the change from baseline is a decrease in QMG score of the patient over time after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment or after administration of the last dose of the pharmaceutical composition of at least 7 points over time. In some embodiments, the change from baseline is a decrease in QMG score of the patient over time of greater than or equal to 8 minutes after treatment 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks or after administration of the last dose of the pharmaceutical composition.

In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in the patient exhibiting a change from baseline over time on the MG-QoL15 score after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment or after the last dose is administered. In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in the patient exhibiting a change in MG-QoL15 score from baseline over time after the last dose is administered. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in the patient exhibiting a transition from baseline over time after treatment 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks or after administration of the last dose on MGFA classification. In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis results in the patient exhibiting a transition in MGFA classification over time after administration of the last dose of the pharmaceutical composition. In some embodiments, the transition is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, or 80%.

In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in a change from baseline on the Neuro-QoL-fatigue scale after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment. In some embodiments, administration of the pharmaceutical composition to pediatric patients to treat myasthenia gravis results in a change from baseline over time on the Neuro-QoL-fatigue scale after administration of the last dose. In some embodiments, a change from baseline on Neuro-QoL-fatigue indicates improvement. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, administration of the pharmaceutical composition to pediatric patients to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in a change in the EQ-5D-5L scale from baseline. In some embodiments, a change from baseline on the EQ-5D-5L scale indicates improvement. In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis results in a change from baseline over time on the EQ-5D-5L scale after treatment 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks or after administration of the last dose. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in a change in EQ-5D-5Y scale from baseline. In some embodiments, a change from baseline on the EQ-5D-5Y scale indicates improvement. In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis results in a change from baseline over time on the EQ-5D-5Y scale after treatment 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks or after administration of the last dose. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in a change in PGI-C scale from baseline. In some embodiments, a change from baseline on the PGI-C scale indicates improvement. In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis results in a change from baseline over time on the PGI-C scale after 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks of treatment or after the last dose is administered. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in a change in PGI-S scale from baseline. In some embodiments, a change from baseline on the PGI-S scale indicates improvement. In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in a change from baseline on the PGI-S scale after treatment 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks or after administration of the last dose. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, administration of the pharmaceutical composition to pediatric patients to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in a change in the C-SSRS scale from baseline. In some embodiments, a change from baseline on the C-SSRS scale indicates improvement. In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in a change from baseline on the C-SSRS scale after treatment 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks or after administration of the last dose over time. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, administering the pharmaceutical composition to a pediatric patient to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in a change in the PedsQL scale from baseline. In some embodiments, a change from baseline on the PedsQL scale indicates improvement. In some embodiments, administration of the pharmaceutical composition to a pediatric patient to treat myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof results in a change from baseline over time on the PedsQL scale after treatment 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 weeks or after administration of the last dose. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1% -20%, 5% -25%, 10% -30%, 15% -35%, 20% -40%, 40% -60%, or about or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95%.

In some embodiments, a subject who is treated for myasthenia gravis, transient neo-natal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof with an anti-FcRn antibody does not experience clinically significant increased levels of total cholesterol, high Density Lipoprotein (HDL), calculated Low Density Lipoprotein (LDL), and triglycerides after treatment with the antibody. In some embodiments, the anti-FcRn antibody is M281. In some embodiments, a subject treated for myasthenia gravis, transient neo-natal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof with an anti-FcRn antibody does not experience clinically significant increased levels of total cholesterol after treatment with the antibody. In some embodiments, a subject who is treated for myasthenia gravis, transient neo-natal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof with an anti-FcRn antibody does not experience clinically significant increased levels of High Density Lipoprotein (HDL) after treatment with the antibody. In some embodiments, a subject with an anti-FcRn antibody for treating myasthenia gravis, transient neo-natal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof does not experience clinically significant increased levels of calculated Low Density Lipoprotein (LDL) after treatment with the antibody. In some embodiments, a subject treated for myasthenia gravis, transient neo-natal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof with an anti-FcRn antibody does not experience clinically significant increased levels of triglycerides after treatment with the antibody. In some embodiments, a subject treated with an anti-FcRn antibody for myasthenia gravis, transient neonatal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof does not experience clinically significant increased levels of total cholesterol after treatment with M281. In some embodiments, a subject treated for myasthenia gravis, transient neo-natal myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof with an anti-FcRn antibody does not experience significantly increased levels of High Density Lipoprotein (HDL) after treatment with M281. In some embodiments, a subject with an anti-FcRn antibody for treating myasthenia gravis, transient neo-infantile myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, does not experience clinically significant increased levels of calculated Low Density Lipoprotein (LDL) after treatment with M281. In some embodiments, a subject treated with an anti-FcRn antibody for myasthenia gravis, transient neo-infantile myasthenia, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof does not experience clinically significant increased levels of triglycerides after treatment with M281.

In some embodiments, administration of the pharmaceutical composition to a patient does not significantly increase the levels of total cholesterol, high Density Lipoprotein (HDL), calculated Low Density Lipoprotein (LDL), and triglycerides after administration of the pharmaceutical composition comprising the antibody. In some embodiments, the significant increase is a clinically significant increase. In some embodiments, the anti-FcRn antibody is M281. In some embodiments, administration of the pharmaceutical composition to the patient does not significantly increase the level of total cholesterol after administration of the pharmaceutical composition comprising the antibody. In some embodiments, administration of the pharmaceutical composition to a patient does not significantly increase the level of High Density Lipoprotein (HDL) after administration of the pharmaceutical composition comprising the antibody. In some embodiments, administration of the pharmaceutical composition to a patient does not significantly increase the calculated level of Low Density Lipoprotein (LDL) after administration of the pharmaceutical composition comprising the antibody. In some embodiments, administration of the pharmaceutical composition to a patient does not significantly increase the level of triglycerides after administration of the pharmaceutical composition comprising the antibody. In some embodiments, administration of the pharmaceutical composition to the patient does not significantly increase the level of total cholesterol after administration of the pharmaceutical composition comprising M281. In some embodiments, administration of the pharmaceutical composition to a patient does not significantly increase the level of High Density Lipoprotein (HDL) after administration of the pharmaceutical composition comprising M281. In some embodiments, administration of the pharmaceutical composition to a patient does not significantly increase the calculated level of Low Density Lipoprotein (LDL) after administration of the pharmaceutical composition comprising M281. In some embodiments, administration of the pharmaceutical composition to a patient does not significantly increase the level of triglycerides after administration of the pharmaceutical composition comprising M281.

As used herein, the phrase "not significantly increased" when used in reference to levels (measured values) of total cholesterol, high Density Lipoprotein (HDL), calculated Low Density Lipoprotein (LDL), or triglyceride means any increase of less than 30% compared to the level prior to administration of the antibody or composition provided herein (baseline). As used herein, the phrase "does not undergo a clinically significant increase" when used in reference to levels (measured values) of total cholesterol, high Density Lipoprotein (HDL), calculated Low Density Lipoprotein (LDL), or triglyceride means that any increase is less than 30% compared to the level prior to administration of the antibody or composition provided herein (baseline). In some embodiments, the increase is less than 25%, 20%, 15%, 10%, or 5%. In some embodiments, the increase is no greater than about 1% to about 30%, about 5% to about 25%, about 1% to about 20%, about 1% to about 15%, about 1% to about 10%, about 5% to about 15%, about 5% to about 20%, about 10% to about 20%, about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, or about 30%.

As used herein, the term "change" with respect to baseline refers to a subject having an improvement in a condition, score, symptom, etc., as compared to the subject prior to treatment with an anti-FcRn antibody as provided herein.

"baseline" refers to a subject prior to treatment with a therapeutic agent (such as an anti-FcRn antibody, including those provided herein).

As provided herein, in some embodiments, the improvement in symptoms or conditions is said to occur 24 weeks after initiation of treatment. Although reference is made to determining whether those improvements can be measured 24 weeks after initiation of treatment, in some embodiments, the improvements or changes described herein will occur within 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 weeks. In some embodiments, the change or improvement will last for at least 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 weeks.

In some embodiments, the subject receiving the myasthenia gravis treatment is a subject in need thereof.

As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

As used herein, the term "about" means that the numerical values are approximate and that small variations will not significantly affect the practice of the disclosed embodiments. Where numerical limits are used, unless the context indicates otherwise, "about" means that the value may vary by + -10% and remain within the scope of the disclosed embodiments.

As used herein, the terms "comprises," "comprising," "and any form of" comprising, "such as" comprises, "" contains, "" including, "and" contains, "" having, "" with, "and any form of" having, "" with, "and" having, "" including, "" and any form of "including," or "containing," are inclusive or open-ended, and do not exclude additional, unrecited elements or method steps. Any composition or method that recites the term "comprising" is also to be understood to also describe such compositions as consisting of, or consisting essentially of the recited components or elements.

As used herein, the terms "individual," "subject," or "patient" are used interchangeably to refer to any animal, including mammals, such as mice, rats, other rodents, rabbits, dogs, cats, pigs, cattle, sheep, horses, or primates, such as humans. As used herein, the term "mammal" refers to a rodent (i.e., mouse, rat, or guinea pig), monkey, cat, dog, cow, horse, pig, or human. In some embodiments, the mammal is a human. In some embodiments, the subject is a pediatric subject.

As used herein, the phrase "in need thereof" means that the subject has been identified as in need of a particular method or treatment. In some embodiments, the identification may be by any diagnostic means. In any of the methods and treatments described herein, the subject may be in need thereof. In some embodiments, the subject is in or is about to travel to an environment in which a particular disease, disorder, or condition is prevalent.

As used herein, the phrase "an integer from X to Y" is meant to include any integer of endpoints. For example, the phrase "an integer of 1 to 5" refers to 1, 2, 3, 4, or 5.

The following examples are illustrative, but not limiting, of the compounds, compositions, and methods described herein. Other suitable modifications and adaptations known to those skilled in the art are within the scope of the following embodiments.

Other embodiments

While the present disclosure has been described in connection with specific embodiments thereof, it will be understood that further modifications are possible, and this application is intended to cover any variations, uses, or adaptations of the application following, in general, the principles and including such departures from the present disclosure as come within known or customary practice within the art to which the disclosure pertains and as may be applied to the essential features hereinbefore set forth.

In some embodiments, embodiments provided herein further include, but are not limited to:

1. a method of treating pediatric myasthenia gravis in a pediatric patient in need thereof, the method comprising administering an initial loading dose of about 30mg/kg to about 60mg/kg of an anti-FcRn antibody followed by a maintenance dose of about 15mg/kg to about 30mg/kg of the anti-FcRn antibody, wherein the anti-FcRn antibody comprises:

heavy chains comprising HCDR1 of SEQ ID NO. 6, HCDR2 of SEQ ID NO. 7 and HCDR3 of SEQ ID NO. 8; and

a light chain comprising LCDR1 of SEQ ID NO. 3, LCDR2 of SEQ ID NO. 4 and LCDR3 of SEQ ID NO. 5;

wherein the administration reduces serum IgG of the patient by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of baseline serum IgG, and

wherein the pediatric myasthenia gravis is selected from temporary neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome, or any combination thereof.

2. The method of embodiment 1, wherein the pediatric myasthenia gravis is temporary neonatal myasthenia.

3. The method of embodiment 1, wherein the pediatric myasthenia gravis is juvenile myasthenia gravis.

4. The method of embodiment 1, wherein the pediatric myasthenia gravis is congenital myasthenia gravis syndrome.

5. The method of embodiment 1, wherein the heavy chain comprises an amino acid sequence having at least 95% identity to the sequence of SEQ ID No. 2 and the light chain comprises an amino acid sequence having at least 95% identity to the sequence of SEQ ID No. 1.

6. The method of embodiment 1, wherein the heavy chain comprises a variable region heavy chain comprising an amino acid sequence having at least 95% identity to the sequence of SEQ ID No. 10 and the light chain comprises a variable region light chain comprising an amino acid sequence having at least 95% identity to the sequence of SEQ ID No. 9.

7. The method of embodiment 1, wherein the heavy chain comprises the amino acid sequence of SEQ ID No. 2 and the light chain comprises the amino acid sequence of SEQ ID No. 1.

8. The method of embodiment 1, wherein the heavy chain comprises a variable region heavy chain comprising the amino acid sequence of SEQ ID No. 10 and the light chain comprises a variable region light chain comprising the amino acid sequence of SEQ ID No. 9.

9. The method of any one of embodiments 1 to 8, wherein the administration is intravenous or subcutaneous.

10. The method of any one of embodiments 1-9, wherein the administering comprises administering a pharmaceutical composition comprising about 10mg/ml to about 60mg/ml of the anti-FcRn antibody, about 20mM to about 30mM sodium phosphate, about 20mM to about 30mM sodium chloride, about 80mg/ml to about 100mg/ml trehalose, and about 0.1% w/v to about 0.005% w/v polysorbate 80.

11. The method of any one of embodiments 1 to 10, wherein the initial loading dose is about 60mg/kg or about 30mg/kg.

12. The method of any one of embodiments 1 to 11, wherein the maintenance dose is about 15mg/kg or about 30mg/kg.

13. The method of any one of embodiments 1 to 12, wherein the maintenance dose is administered in the following manner:

1 week, 2 weeks, 3 weeks, 4 weeks, or monthly following the administration of the initial loading dose; and

1 week, 2 weeks, 3 weeks, 4 weeks, or monthly following the administration of the previous maintenance dose.

14. The method of any one of embodiments 1 to 13, wherein:

infusing the initial loading dose into the pediatric patient for about 30 minutes to about 90 minutes; and is also provided with

The maintenance dose is infused into the pediatric patient within about 15 minutes to about 60 minutes.

15. The method of any one of embodiments 1 to 14, wherein the serum IgG is IgG1, igG2, igG3, or IgG4, or any combination thereof, and wherein the decrease is at least 20% of baseline, or at least 30% of baseline.

16. The method of any one of embodiments 1-15, wherein the administration of the anti-FcRn antibody reduces serum albumin by at most 18%, at most 16%, at most 14%, at most 12%, at most 10%, at most 8%, at most 6%, at most 4%, or at most 2% of a serum albumin baseline.

17. The method of any one of embodiments 1 to 16, wherein the administering reduces serum autoantibodies, wherein:

the autoantibody is selected from the group consisting of: anti-acetylcholine receptor (AChR), anti-muscle-specific kinase (MuSK), anti-low density lipoprotein receptor-related protein 4 (LRP 4), anti-human collectin, anti-actin, anti-kv 1.4, anti-ranitidine receptor, anti-collagen Q, and anti-actin; and is also provided with

The reduction is at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 50%, or at least 25% of baseline serum autoantibodies.

18. The method of embodiment 17, wherein the administration of the anti-FcRn antibody reduces an anti-AChR antibody by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 50%, or at least 25% of a baseline anti-AChR antibody.

19. The method of any one of embodiments 17 or 18, wherein the administration of the anti-FcRn antibody reduces an anti-MuSK antibody by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 50%, or at least 25% of a baseline anti-MuSK antibody.

20. The method of any one of embodiments 1-19, wherein the patient achieves a change in MG-ADL score, QMG score, neuro-QoL-fatigue score, EQ-5D-5Y score, PGI-C score, PGI-S score, pedsQL score, or any combination thereof from baseline.

21. The method of any one of embodiments 1-20, wherein the administration of the anti-FcRn antibody to the pediatric patient does not significantly increase the levels of total cholesterol, HDL, calculated LDL, and triglycerides in the subject compared to the level prior to the administration of the anti-FcRn antibody.

22. A pharmaceutical composition comprising an anti-FcRn antibody for administration to a pediatric patient suffering from pediatric myasthenia gravis, wherein:

administering the anti-FcRn antibody intravenously or subcutaneously to the pediatric patient at an initial loading dose of about 30mg/kg to about 60mg/kg followed by administration of a maintenance dose of about 15mg/kg to about 30mg/kg of the anti-FcRn antibody; and is also provided with

The anti-FcRn antibody comprises:

a light chain comprising LCDR1 of SEQ ID NO. 3, LCDR2 of SEQ ID NO. 4 and LCDR3 of SEQ ID NO. 5; and is also provided with

23. The pharmaceutical composition of embodiment 22, wherein the initial loading dose is about 60mg/kg or about 30mg/kg, and wherein the maintenance dose is about 15mg/kg or about 30mg/kg.

24. The pharmaceutical composition of embodiment 22, wherein the pediatric myasthenia gravis is temporary neonatal myasthenia.

25. The pharmaceutical composition of embodiment 22, wherein the pediatric myasthenia gravis is juvenile myasthenia gravis.

26. The pharmaceutical composition of embodiment 22, wherein the pediatric myasthenia gravis is congenital myasthenia gravis syndrome.

The following examples are illustrative, but not limiting, of the methods and compositions described herein. Other suitable modifications and adaptations known to those skilled in the art are within the scope of the following embodiments.

Examples

Example 1. Study design.Evaluation of ongoing, stabilization in a pair with gMGPharmacokinetic (PK), pharmacodynamic (PD), safety, tolerability, efficacy of study drug and activity of intravenous nicarbazin in pediatric subjects (2 years to less than 18 years) with inadequate clinical response, phase 2/3, open label, multicenter study.

A screening period of up to 28 days allows sufficient time to perform screening evaluations and determine study qualification.

A total of 12 subjects were presented, 6 in each of the two age groups: group 1) =12 to <18 years old; and group 2) > = 2 years to <12 years old.

The active treatment phase included group 1 and group 2, which were blinded and open to all male and female pediatric subjects meeting study-specific inclusion and exclusion criteria. The study population will include boys and girls diagnosed with gMG with systemic muscle weakness who have inadequate clinical response to ongoing, stable standard of care treatment and who meet gMG clinical criteria defined by the american Myasthenia Gravis Foundation (MGFA) clinical classification group II a/b, group III a/b or group IV a/b at the time of screening. In addition, participants will perform a positive serological test for gMG-associated pathogenic autoantibodies (anti AChR and/or anti MuSK).

Pediatric patients will be excluded from the following study: 1) There is a history of severe and/or uncontrolled liver, gastrointestinal, kidney, lung, cardiovascular, psychiatric, neurological or musculoskeletal disorders or any other medical condition (including laboratory abnormalities) that, from the point of view of the researcher, may interfere with the participant's complete participation in the research or may jeopardize the participant's safety or the effectiveness of the research results. 2) With any confirmed or suspected clinical immunodeficiency syndrome, independent of his/her gMG treatment, or with a family history of congenital or genetic immunodeficiency, unless confirmed to be absent in the participants. 3) There are MGFA class I diseases or MG crisis present at screening (MGFA class V), MG crisis history or fixed weakness (and/or "burn out)" MG within 1 month of screening. 4) Depending on stomach tube to meet nutrition requirement or depending on breathing machine. 5) Radiation therapy or chemotherapy is actively being performed due to unresectable/malignant thymomas. After discussion with sponsors' medical inspectors, participants with stable benign thymomas (e.g., stage I or IIa) that were not treated for the last 3 years may be allowed. 6) Thymic resections were performed within 12 months prior to screening or were planned during the active treatment period of the study. 7) Current or medical history of any neurological condition other than MG that may interfere with the accuracy of the study evaluation, including but not limited to any chronic neurodegenerative disease, altered level of consciousness, dementia, abnormal mental state, major congenital neurological deficit, lambert-eaton myasthenia syndrome (Lambert-Eaton myasthenic syndrome), drug-induced MG, or hereditary forms of myasthenia syndrome. 8) The present day has malignancy or a history of malignancy within 3 years of screening (with the exception of localized basal cell carcinoma and/or squamous cell carcinoma skin carcinoma that has been adequately treated with no evidence of recurrence at least 3 months [ defined as at least 12 weeks ] prior to the first study intervention administration, or cervical carcinoma in situ that has been treated with no evidence of recurrence at least 3 months prior to the first study intervention administration). 9) Subjects are known to be allergic, hypersensitive or intolerant to nicalimab or its excipients (referred to as IB). 10 Has been shown to be previously severe in immediate hypersensitivity, such as anaphylaxis to therapeutic proteins (e.g., monoclonal antibodies). 11 Myocardial infarction, unstable ischemic heart disease or stroke within 12 weeks of screening. 12 Past/concomitant treatment: igG Fc-related protein therapeutics or Fc-conjugated therapeutics, including factor or enzyme substitutes, are currently being administered. Rituximab was received within 6 months prior to the first administration study intervention. Live vaccine was received 3 months prior to screening, or it was known that live vaccine was required during the study, or at least 3 months after the last study intervention. Plasmapheresis, immunoadsorption therapy or IVIg was received within 4 weeks prior to baseline. There is another medical condition requiring oral or parenteral corticosteroids unless the dose has been stable for at least 4 weeks prior to baseline and is expected to remain stable during the study. Inhaled, intra-articular, topical or ocular corticosteroids are not excluded. The dose has been stabilized for at least 3 months prior to baseline unless the drug has been used for at least 6 months, and the drug and the dose are expected to remain stable during the study. Nicarbazin was previously received. 13 Infection or susceptibility to infection: have severe infections, including opportunistic infections requiring parenteral anti-infective drugs and/or hospitalization (e.g., pneumonia, biliary tract infections, diverticulitis, clostridium difficile infection (Clostridium difficile infection), cytomegalovirus, pneumosporosis, aspergillosis, etc.), and/or are assessed as severe/clinically significant by researchers within 8 weeks prior to screening. After the 8-week exclusion period has elapsed, the participants can be rescreened. Has chronic infections (e.g., bronchiectasis, chronic osteomyelitis, chronic pyelonephritis) or requires long-term treatment with anti-infective agents (e.g., antibiotics, antivirals). Hepatitis B Virus (HBV) infection tests positive. Antibodies to Hepatitis C Virus (HCV) are seropositive unless they meet 1 of the following conditions: a history of successful treatment, defined as negative for HCV RNA at least 24 weeks after antiviral treatment is completed and negative for HCV RNA detection at the time of screening, or, although seropositive, at least 24 weeks prior to screening and negative for HCV RNA detection at the time of screening. A history of Human Immunodeficiency Virus (HIV) 1 or HIV2 antibody positivity, or a test positive for HIV at the time of screening.

The study consisted of a screening period of up to 4 weeks, an active treatment period of 24 weeks and a Long Term Extension (LTE) period.

Teenagers (age 12 years to <18 years) were enrolled in group 1 to evaluate PK, PD, safety and activity of study drug treatments. Twelve weeks after all participants entered group 1, medium term analysis assessed PK, PD and safety data, if acceptable, and study was started in group 2 (participants 2 to <12 years old). Once teenagers are recruited, young subjects aged 2 years to <12 years may be recruited. Study drug was administered to all subjects via IV infusion every two weeks over 15-30 minutes. Participants in study group 1 received a single 30mg/kg loading dose followed by 15mg/kg every 2 weeks [ q2w ]. Dosing for group 2 was modeled based on all existing PK and PD data available at mid-term analysis, including adult data from phase 1 to phase 3 studies and adolescent data from this study group 1. A total of at least 12 subjects were studied, with at least 6 in each of the two age groups (adolescents and younger children).

Study duration was 24 weeks, optionally entering Long Term Extension (LTE) after study completion; subjects who were either early discontinued or did not enter LTE after completion of the study were subjected to safety assessment 8 weeks after termination of their recruitment. LTE is expected to be approximately 104 weeks (about 2 years) in duration. All group 1 participants in the LTE phase of the study had the option of either receiving q2w (15 mg/kg) or q4w (30 mg/kg) of nicarbazin infusion or changing the background concomitant drug (based on the study's judgment). The option of changing the dose and regimen of group 2 participants during the LTE phase was modeled and based on all existing PK and PD data available at the mid-term analysis (including adult data from phase 1 to phase 3 studies and juvenile data from this study group 1). No other dosing regimen should be used. Participants who were either early discontinued or did not enter LTE after completion of the study were given a safety follow-up visit 8 weeks after their last infusion study stem.

To evaluate PK and PD of study drug in pediatric participants with gMG, blood samples were collected at selected visits in the study. Serum samples for immunogenicity assessment were collected at selected visits in this study. Biomarker samples were collected to evaluate the mechanism of action of study drugs or to help identify subgroups of populations that respond differently to intervention.

The duration of the active treatment phase (24 weeks) was expected to be sufficient to evaluate activity and safety based on the mechanism of action of nicroliab and the results of an adult 2-phase study that demonstrated efficacy of MG-ADL as early as week 2 and continued until day 57 (the main evaluation time point in the adult 2-phase study). Maintenance of nicarbazin effect and long-term safety of nicarbazin was further assessed during the LTE phase.

Main study parameters/results: effect of nicroliab on total serum IgG of pediatric participants with gMG aged 2 to <18 years with inadequate clinical response to ongoing, stable standard-of-care treatment. Safety and tolerability of treatment with nica Li Shan in pediatric participants with gMG from 2 years to <18 years with inadequate clinical response to ongoing, stable standard of care treatment. Nicalimumab pharmacokinetics in pediatric participants with gMG ages 2 to <18 years with inadequate clinical response to ongoing, stable standard-of-care treatment. All primary PK and IgG endpoints will be summarized descriptive over time for the evaluable population and each age group (2 to <12 years, or 12 to <18 years).

Secondary endpoints include: nicarbazin activity in gMG as measured by a change in myasthenia gravis-activities of daily living (MG-ADL) efficacy score from baseline. The activity of nicroliumab in gMG as measured by the change in Quantitative Myasthenia Gravis (QMG) efficacy score from baseline. Impact on quality of life as measured by the young european quality of life 5-dimensional (EQ-5D-Y) tool. Effects on fatigue as measured by the quality of life of nerves (Neuro-QoL) pediatric fatigue score. All secondary endpoints will be descriptive summarised over time for the evaluable population and each age group (2 to <12 years, or 12 to <18 years).

Exploratory endpoints include: the relationship between nicalicheating amount, nicalix Li Shan anti-PK, total serum IgG, MG-ADL score and QMG score as assessed by PK-PD model. Effects of nica Li Shan anti-treatment on autoantibody levels (anti AChR and anti MuSK). Impact on health-related quality of life as measured by the pediatric quality of life scale (PedsQL). All exploratory endpoints will be summarized descriptive over time and for each age group (2 to <12 years, or 12 to <18 years).

Safety assessments include AE and SAE collection, concomitant drug use, clinical laboratory tests (including chemical, hematological, lipid profile, urine tests, and tests of total serum IgG and vaccine titers against diphtheria/tetanus), ECG, vital signs, physical examination, and Tanner stage. Urine pregnancy tests were only performed on girls with fertility. In addition, the occurrence of suicide ideas was assessed using the Columbia suicide severity rating scale (C-SSRS). Severe or critical infections, hypoalbuminemia events (< 20 g/L) and opportunistic infections are considered adverse events of particular concern (AESI).

Example 2 nicarbazin is safe and well tolerated in patients with gMG. Prior to treatment with nicrolib, pediatric subjects were evaluated using one or more of the following: physical examination, C-SSRS, vital signs, 12-lead ECG, and urine examination. In addition, blood and serum were collected for exploratory biomarker analysis, ig-type analysis, and clinical laboratory evaluation. Prior to treatment with nicrolimus, subjects with myasthenia gravis or subjects with gMG who did not have sufficient clinical response to ongoing, stable standard of care treatment were evaluated using physical examination, C-SSRS, vital signs, 12-lead ECG, urine test, blood and serum evaluation tests to generate baseline scores. Nicorandil was administered to subjects every 2 weeks in a single dose or loading dose and maintenance dose for 24 weeks. After 24 weeks, and throughout the study, subjects were evaluated for changes in vital signs, clinical laboratory values, and C-SSRS scores.

Example 3 modeling of intravenous administration. Various dosing regimens for M281 were modeled based on clinical data from adolescent patients. The effects of various dosing regimens on myasthenia gravis activities of daily living (MG-ADL) were modeled. The modeled dose was: about 5mg/kg, about 10mg/kg, about 15mg/kg, about 20mg/kg, about 25mg/kg, about 30mg/kg, about 40mg/kg, about 45mg/kg, about 50mg/kg, about 55mg/kg, about 60mg/kg. Based on this modeling, dosing regimens for younger patients were derived.

Example 4 treatment of myasthenia gravis with anti-FcRn antibodies resulted in a change from baseline on the MG-ADL scale. Pediatric subjects were evaluated using the myasthenia gravis-daily life activity (MG-ADL) scale prior to treatment with nicrolimus. MG-ADL assessment was used to generate MG-ADL scores for subjects with myasthenia gravis or subjects with gMG who did not have sufficient clinical response to ongoing, stable standard of care treatment prior to treatment with nicarlizumab. Nicarbazin is administered to the subject every 2 weeks in a single dose or loading dose and maintenance dose,for 24 weeks. After 24 weeks, and throughout the study, subjects were evaluated for changes in MG-ADL scores at day 1, week 2, week 3, week 4, week 6, week 8, week 12, week 16, week 18, week 20, week 22, week 23, and week 24. After 24 weeks, and throughout the study, subjects were evaluated using the MG-ADL scale and found to show a change from baseline on the MG-ADL scale.

Example 5 treatment of myasthenia gravis with anti-FcRn antibodies resulted in a baseline on the QMG and MG-QOL15r scales Variation of. The subjects were evaluated using QMG and MG-QoL15r scales prior to treatment with nicroliab. Prior to treatment with nicrolimus, QMG and MG-QoL15r were used to evaluate subjects suffering from myasthenia gravis or subjects suffering from gMG who did not have sufficient clinical response to ongoing, stable standard of care treatment to generate QMG and MG-QoL15r scores. Nicorandil was administered to subjects every 2 weeks in a single dose or loading dose and maintenance dose for 24 weeks. After 24 weeks, and throughout the study, subjects were evaluated for changes in QMG and MG-QoL15r scores at day 1, week 2, week 4, week 8, week 12, week 16, week 20, week 22, and week 24. After 24 weeks, and throughout the study, subjects were evaluated using QMG and MG-QoL15r scales, and found to show a change from baseline on QMG and MG-QoL15r scales.

Example 6 treatment of myasthenia gravis with anti-FcRn antibodies resulted in fatigue in Neuro-QoL-pediatric, EQ-5D-5Y, Changes from baseline on MGFA, PGI-C, PGI-S and PedsQL scales. Pediatric subjects were evaluated using the Neuro-QoL-pediatric fatigue (senior group only), EQ-5D-5Y (senior group only), MGFA, PGI-C (senior group only), PGI-S (senior group only), and the PedsQL scale prior to treatment with nicaliab. Prior to treatment with nicalizumab, neuro-QoL-fatigue (senior group only), EQ-5D-5Y (senior group only), MGFA, PGI-C (senior group only), PGI-S (senior group only) and the PedsQL scale were used to evaluate infants suffering from myasthenia gravis with inadequate clinical response to ongoing, stable standard of care treatmentSubjects or subjects suffering from gMG to generate Neuro-QoL-pediatric fatigue (senior group only), EQ-5D-5Y (senior group only), MGFA, PGI-C (senior group only), PGI-S (senior group only), and petsql scores. Nicarbazin was administered to pediatric subjects every 2 weeks in a single dose or loading dose and maintenance dose for 24 weeks. After 24 weeks, and throughout the study, pediatric subjects were evaluated for changes in Neuro-QoL-pediatric fatigue, EQ-5D-5Y, PGI-C, PGI-S, and PedsQL scores on day 1 (except PGI-C), week 2, week 4, week 8, week 12, week 16, week 20, week 22, and week 24. After 24 weeks, and at day 1 and week 12 throughout the study, pediatric subjects were evaluated for changes in MGFA scores. After 24 weeks, and throughout the study, pediatric subjects were evaluated using the Neuro-QoL-pediatric fatigue, EQ-5D-5Y, MGFA, PGI-C, PGI-S, and PedsQL scales, and changes from baseline were found to be achieved on the Neuro-QoL-pediatric fatigue, EQ-5D-5Y, MGFA, PGI-C, PGI-S, and PedsQL scales.

EXAMPLE 7 treatment of pediatric myasthenia with Nical Li Shan anti-treatment of pediatric myasthenia does not raise cholesterol to clinically significant levels. More recently, the use of another experimental anti-FcRn antibody that is not nicrolimab in the same pharmacological class of FcRn antagonists has been reported to increase total cholesterol and Low Density Lipoprotein (LDL). This finding triggered a review of lipid data in the sponsor completed and ongoing nica Li Shan anti-study. In healthy volunteers at stage 1 and systemic myasthenia gravis study at stage 2, asymptomatic, dose-dependent, reversible elevation of non-fasting average total cholesterol was observed, up to 25% of baseline. At the highest dose of 60mg/kg every 2 weeks (Q2W), the average percent change in total cholesterol increases to a stable maximum of 21% to 23% above baseline within 1 month of initial dosing and decreases to near baseline levels 1-2 months after the last dose. As a result of these findings, the following evaluations were performed: 1) lipid assessment (total cholesterol, HDL, calculated LDL and triglycerides) at various time points at treatment and cessation of treatment under fasting and non-fasting conditions, 2) exclusion criteria for patients with recent significant cardiovascular events, 3) recommendation of lipid abnormality management according to local health guidelines.

Example 8 pediatric dose adjustment. The recommended dose level and dosing regimen for group 1 of this phase 2/3 study in adolescent participants with gMG (i.e., 30mg/kg IV load dose on day 1 followed by 15mg/kg IV q2w maintenance dose from week 2) was based on the dose level and dosing regimen selected for phase 3 study in adult participants with gMG. Dose levels and dosing regimens for the adult stage 3 gMG study were based on data observed from the adult stage 2 study in participants with gMG and extensive modeling and simulation of dose response relationships for IgG and MG-ADL using data from adult stage 1 and 2 studies. As set forth in example 1, dosing of group 2 of the present study was modeled based on all existing PK and PD data available at the mid-term analysis, including adult data from phase 1 to phase 3 studies and adolescent data from the present study group 1. In the adult 2 gMG study, a rapid dose-dependent IgG decrease was observed one week after the initial dose in all dose groups, with a maximum IgG decrease reached at week 2 in the 60mg/kg single dose and 60mg/kgq2w groups. Dose-dependent improvement in MG-ADL scores was also observed, indicating a correlation between IgG reduction and improvement in MG-ADL scores. Importantly, nicarbazin was generally well tolerated in all dose groups. Population PK/PD/efficacy modeling analysis was performed using data obtained from the nica Li Shan anti-adult stage 1 and stage 2 studies to evaluate the relationship between PK, igG reduction, and MG-ADL, among other efficacy and safety endpoints, including serum albumin and cholesterol. The results indicate that the q2w dosing interval will provide more sustained IgG reduction and MG-ADL reduction at all simulated dose levels when compared to the q4w dosing interval. Although modeling and simulation showed numerical differences in IgG reduction and MG-ADL reduction between 15MG/kg and 30MG/kg q2w dosing regimens (model predicted average IgG reduction of 73.8% versus 79.4%, respectively), the additional 5.6% IgG reduction of 30MG/kgq2w was converted to the minimal additional MG-ADL improvement at the steady state trough, exceeding the improvement expected for 15MG/kg q2w (fig. 1). Thus, a 15mg/kg q2w dosing regimen was chosen as the single maintenance dose regimen for the adult 3-stage gMG study, as this is a rare disease with highly unmet needs. Lower doses may result in Suboptimal efficacy, while higher doses may not produce a large difference in efficacy as predicted for gMG. The predicted exposure at day 1 at the 30mg/kg IV load dose followed by the 15mg/kg IV q2w maintenance dose was much lower than the PK exposure observed in the adult 2gMG phase study from the 60mg/kg q2w dosing regimen, which is generally well tolerated based on the safety data currently available. The dosing regimen for the adult 3 gMG study program was expected to have an average at steady state<Albumin reduction by 20% and<total cholesterol increased by 20%. The magnitude of albumin reduction and total cholesterol increase was expected to be clinically insignificant and less than those observed in previous adult studies on 30mg/kg IV or 60mg/kg IV q2w dose regimen per week. Thus, the recommended dose for the adult 3-phase gMG study was expected to be safe and well tolerated. To propose a dose regimen for adolescent participants with gMG, the population PK/Receptor Occupancy (RO)/IgG model was developed using data from adults, and this model was suitable for dose selection in pediatric participants with gMG. Based on data from literature, the adapted model demonstrated 1) lower Clearance (CL) and distribution volume (V) in pediatric patients: CL and V are measured by body weight according to abnormal growth; 2) Age and/or weight dependent FcRn and IgG at baseline in pediatric patients: fcRn and IgG are measured by age and/or weight (Hardiansyah 2018). The results from the model-based simulations demonstrate comparable PK and IgG curves between adolescents and adult patients with gMG when treated with the proposed doses and dosing regimen (fig. 2). Thus, the dose and dosing regimen selected for the adult 3 gMG study was also used in group 1 of the study from 12 years old to <Teenager patients aged 18 years and without adjustment of the dose. After the teenager participants in group 1 completed the first 12 weeks of their treatment with nicarbazin, an interim analysis was performed to evaluate PK, PD and safety data. Children in group 2 (2 years to age)<12 years old) was selected based on PK-PD modeling and simulation using all existing PK and PD data available at mid-term analysis (including adult data from phase 1 to phase 3 studies and adolescent data from study group 1). In metaphase PK-PD modeling and simulation, CL and V are measured in terms of body weight or Body Surface Area (BSA)While FcRn and IgG will be measured in terms of age, weight or BSA. Based on the results from the interim analysis, dose adjustments may be required for children in group 2.

The embodiments and examples provided herein demonstrate that anti-FcRn antibodies, such as but not limited to nicrolimus, are effective in treating myasthenia gravis as measured by one or more of the indices and results provided herein.

The disclosures of each patent, patent application, and patent publication cited herein are hereby incorporated by reference in their entirety. Although various embodiments have been disclosed with reference to specific aspects, it will be apparent to those skilled in the art that other aspects and modifications of these embodiments can be made without departing from the true spirit and scope of the embodiments. It is intended that the following claims be interpreted to embrace all such aspects and equivalents.

Sequence listing

<110> yansen biotechnology company (Janssen Biotech, inc.)

Black, Shawn

Ramchandren, Sindhu

Zhu, Yaowei

<120> compositions and methods for treating pediatric myasthenia gravis

<130> 258199.001202

<150> 63/173,919

<151> 2021-04-12

<150> 63/219,155

<151> 2021-07-07

<150> 63/266,880

<151> 2022-01-18

<160> 26

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Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe

225 230 235 240

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

245 250 255

Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val

260 265 270

Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

275 280 285

Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val

290 295 300

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

305 310 315 320

Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser

325 330 335

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

340 345 350

Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360 365

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375 380

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

385 390 395 400

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

405 410 415

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425 430

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

435 440 445

<210> 3

<211> 14

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 3

Thr Gly Thr Gly Ser Asp Val Gly Ser Tyr Asn Leu Val Ser

1 5 10

<210> 4

<211> 7

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 4

Gly Asp Ser Glu Arg Pro Ser

1 5

<210> 5

<211> 10

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 5

Ser Ser Tyr Ala Gly Ser Gly Ile Tyr Val

1 5 10

<210> 6

<211> 5

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 6

Thr Tyr Ala Met Gly

1 5

<210> 7

<211> 14

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 7

Ser Ile Gly Ala Ser Gly Ser Gln Thr Arg Tyr Ala Asp Ser

1 5 10

<210> 8

<211> 7

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 8

Leu Ala Ile Gly Asp Ser Tyr

1 5

<210> 9

<211> 110

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 9

Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln

1 5 10 15

Ser Ile Thr Ile Ser Cys Thr Gly Thr Gly Ser Asp Val Gly Ser Tyr

20 25 30

Asn Leu Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu

35 40 45

Met Ile Tyr Gly Asp Ser Glu Arg Pro Ser Gly Val Ser Asn Arg Phe

50 55 60

Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu

65 70 75 80

Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Gly Ser

85 90 95

Gly Ile Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu

100 105 110

<210> 10

<211> 116

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 10

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Ala Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ser Ile Gly Ala Ser Gly Ser Gln Thr Arg Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Leu Ala Ile Gly Asp Ser Tyr Trp Gly Gln Gly Thr Met Val

100 105 110

Thr Val Ser Ser

115

<210> 11

<400> 11

000

<210> 12

<211> 5

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 12

Asn Tyr Ala Met Gly

1 5

<210> 13

<400> 13

000

<210> 14

<211> 14

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 14

Ser Ile Gly Ala Ser Gly Ala Gln Thr Arg Tyr Ala Asp Ser

1 5 10

<210> 15

<211> 14

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 15

Ser Ile Gly Ala Ser Gly Gly Gln Thr Arg Tyr Ala Asp Ser

1 5 10

<210> 16

<400> 16

000

<210> 17

<400> 17

000

<210> 18

<400> 18

000

<210> 19

<400> 19

000

<210> 20

<400> 20

000

<210> 21

<400> 21

000

<210> 22

<400> 22

000

<210> 23

<211> 445

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 23

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Ala Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ser Ile Gly Ser Ser Gly Ala Gln Thr Arg Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Leu Ala Ile Gly Asp Ser Tyr Trp Gly Gln Gly Thr Met Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe

225 230 235 240

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

245 250 255

Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val

260 265 270

Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

275 280 285

Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val

290 295 300

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

305 310 315 320

Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser

325 330 335

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

340 345 350

Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360 365

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375 380

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

385 390 395 400

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

405 410 415

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425 430

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

435 440 445

<210> 24

<211> 445

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 24

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr

20 25 30

Ala Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ser Ile Gly Ala Ser Gly Ser Gln Thr Arg Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Leu Ala Ile Gly Asp Ser Tyr Trp Gly Gln Gly Thr Met Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe

225 230 235 240

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

245 250 255

Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val

260 265 270

Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

275 280 285

Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val

290 295 300

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

305 310 315 320

Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser

325 330 335

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

340 345 350

Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360 365

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375 380

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

385 390 395 400

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

405 410 415

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425 430

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

435 440 445

<210> 25

<211> 445

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 25

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr

20 25 30

Ala Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ser Ile Gly Ala Ser Gly Ala Gln Thr Arg Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Leu Ala Ile Gly Asp Ser Tyr Trp Gly Gln Gly Thr Met Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe

225 230 235 240

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

245 250 255

Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val

260 265 270

Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

275 280 285

Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val

290 295 300

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

305 310 315 320

Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser

325 330 335

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

340 345 350

Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360 365

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375 380

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

385 390 395 400

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

405 410 415

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425 430

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

435 440 445

<210> 26

<211> 445

<212> PRT

<213> artificial sequence

<220>

<223> synthetic sequence

<400> 26

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

20 25 30

Ala Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ser Ile Gly Ala Ser Gly Gly Gln Thr Arg Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Leu Ala Ile Gly Asp Ser Tyr Trp Gly Gln Gly Thr Met Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155 160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe

225 230 235 240

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

245 250 255

Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val

260 265 270

Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

275 280 285

Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val

290 295 300

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

305 310 315 320

Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser

325 330 335

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

340 345 350

Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360 365

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375 380

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

385 390 395 400

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

405 410 415

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425 430

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

435 440 445

Claims

2. The method of claim 1, wherein the pediatric myasthenia gravis is temporary neonatal myasthenia.

3. The method of claim 1, wherein the pediatric myasthenia gravis is juvenile myasthenia gravis.

4. The method of claim 1, wherein the pediatric myasthenia gravis is congenital myasthenia gravis syndrome.

5. The method of claim 1, wherein the heavy chain comprises an amino acid sequence having at least 95% identity to the sequence of SEQ ID No. 2 and the light chain comprises an amino acid sequence having at least 95% identity to the sequence of SEQ ID No. 1.

6. The method of claim 1, wherein the heavy chain comprises a variable region heavy chain comprising an amino acid sequence having at least 95% identity to the sequence of SEQ ID No. 10 and the light chain comprises a variable region light chain comprising an amino acid sequence having at least 95% identity to the sequence of SEQ ID No. 9.

7. The method of claim 1, wherein the heavy chain comprises the amino acid sequence of SEQ ID No. 2 and the light chain comprises the amino acid sequence of SEQ ID No. 1.

8. The method of claim 1, wherein the heavy chain comprises a variable region heavy chain comprising the amino acid sequence of SEQ ID No. 10 and the light chain comprises a variable region light chain comprising the amino acid sequence of SEQ ID No. 9.

9. The method of any one of claims 1 to 8, wherein the administration is intravenous or subcutaneous.

10. The method of any one of claims 1-9, wherein the administering comprises administering a pharmaceutical composition comprising about 10mg/ml to about 60mg/ml of the anti-FcRn antibody, about 20mM to about 30mM sodium phosphate, about 20mM to about 30mM sodium chloride, about 80mg/ml to about 100mg/ml trehalose, and about 0.1% w/v to about 0.005% w/v polysorbate 80.

11. The method of any one of claims 1 to 10, wherein the initial loading dose is about 60mg/kg or about 30mg/kg.

12. The method of any one of claims 1 to 11, wherein the maintenance dose is about 15mg/kg or about 30mg/kg.

13. The method of any one of claims 1 to 12, wherein the maintenance dose is administered by:

14. The method of any one of claims 1 to 13, wherein:

15. The method of any one of claims 1 to 14, wherein the serum IgG is IgG1, igG2, igG3, or IgG4, or any combination thereof, and wherein the decrease is at least 20% of baseline, or at least 30% of baseline.

16. The method of any one of claims 1-15, wherein the administration of the anti-FcRn antibody reduces serum albumin by at most 18%, at most 16%, at most 14%, at most 12%, at most 10%, at most 8%, at most 6%, at most 4%, or at most 2% of a serum albumin baseline.

17. The method of any one of claims 1 to 16, wherein the administering reduces serum autoantibodies, wherein:

18. The method of claim 17, wherein the administration of the anti-FcRn antibody reduces an anti-AChR antibody by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 50%, or at least 25% of a baseline anti-AChR antibody.

19. The method of any one of claims 17 or 18, wherein the administration of the anti-FcRn antibody reduces an anti-MuSK antibody by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 50%, or at least 25% of a baseline anti-MuSK antibody.

20. The method of any one of claims 1-19, wherein the patient achieves a change in MG-ADL score, QMG score, neuro-QoL-fatigue score, EQ-5D-5Y score, PGI-C score, PGI-S score, pedsQL score, or any combination thereof from baseline.

21. The method of any one of claims 1-20, wherein the administration of the anti-FcRn antibody to the pediatric patient does not significantly increase the levels of total cholesterol, HDL, calculated LDL, and triglycerides in a subject compared to the level prior to the administration of the anti-FcRn antibody.

The anti-FcRn antibody comprises:

23. The pharmaceutical composition of claim 22, wherein the initial loading dose is about 60mg/kg or about 30mg/kg, and wherein the maintenance dose is about 15mg/kg or about 30mg/kg.

24. The pharmaceutical composition of claim 22, wherein the pediatric myasthenia gravis is temporary neonatal myasthenia.

25. The pharmaceutical composition of claim 22, wherein the pediatric myasthenia gravis is juvenile myasthenia gravis.

26. The pharmaceutical composition of claim 22, wherein the pediatric myasthenia gravis is congenital myasthenia gravis syndrome.