Compositions and methods for treating pediatric myasthenia gravis

Abstract

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

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Application No. 63 / 173,919, filed April 12, 2021, U.S. Provisional Application No. 63 / 219,155, filed July 7, 2021, and U.S. Provisional Application No. 63 / 266,880, filed January 18, 2022, each of which is incorporated by reference in its entirety herein.

[0002] (Sequence Listing) This application contains a Sequence Listing that has been submitted electronically in ASCII format, which is incorporated herein by reference in its entirety. This ASCII copy was created on April 7, 2022, is named 258199_001202_ST25.txt, and is 26,081 bytes in size.

[0003] FIELD OF THEINVENTION This application relates to treating pediatric patients with myasthenia gravis. [Background technology]

[0004] Myasthenia gravis (MG), with a prevalence of 15–25 cases per 100,000 and an annual incidence of 0.8–1 case per 100,000, is a rare, heterogeneous neuromuscular disease characterized by fluctuating, easily fatigable muscle weakness. Weakness most often affects the ocular, bulbar, proximal limbs, neck, and respiratory muscles, fluctuates during the day, and is exacerbated by fatigue, repetitive activity, fever, infection, and stress. In most cases, initial symptoms are ocular and include ptosis and diplopia, but within 2–3 years of onset, the disease usually worsens and other muscles become affected. This is called generalized MG (gMG). Additional symptoms typically include difficulty chewing, dysphagia, dysarthria, dysphonia, difficulty breathing, inability to keep the mouth closed, a "tooth-baring" expression when trying to smile, the appearance of sadness or drowsiness, difficulty in holding the head upright, and weakness of the arms and legs. Disease progression is associated with significant morbidity from aspiration, increased incidence of respiratory infections and falls, and side effects of immunosuppressive therapy. Furthermore, respiratory muscle weakness can lead to myasthenia gravis crisis, which can be life-threatening and may require hospitalization, mechanical ventilation, tube feeding, fast-acting immunosuppressants, and intensive care. Myasthenia gravis crisis is also associated with additional infectious and cardiovascular complications that contribute to the risk of morbidity and mortality. Summary of the Invention

[0005] There is a significant unmet need for treatment options for patients suffering from MG. The embodiments provided herein meet these needs, as well as others.

[0006] In some embodiments, methods of treating pediatric myasthenia gravis in a pediatric patient in need of treatment are provided. In some embodiments, the method comprises administering an initial loading dose of about 30 mg / kg to about 60 mg / kg of an anti-FcRn antibody, followed by a maintenance dose of about 15 mg / kg to about 30 mg / kg of an anti-FcRn antibody, wherein the anti-FcRn antibody comprises a heavy chain comprising an HCDR1 of SEQ ID NO: 6, an HCDR2 of SEQ ID NO: 7, and an HCDR3 of SEQ ID NO: 8, and a light chain comprising an LCDR1 of SEQ ID NO: 3, an LCDR2 of SEQ ID NO: 4, and an LCDR3 of SEQ ID NO: 5, wherein the administration reduces serum IgG in 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 transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome, or any combination thereof.

[0007] In some embodiments, a pharmaceutical composition comprising an anti-FcRn antibody is provided for administration to a pediatric patient suffering from pediatric myasthenia gravis. In some embodiments, the pharmaceutical composition comprising an anti-FcRn antibody is administered intravenously or subcutaneously to a pediatric patient at an initial loading dose of about 30 mg / kg to about 60 mg / kg, followed by administration of a maintenance dose of about 15 mg / kg to about 30 mg / kg of an anti-FcRn antibody, the anti-FcRn antibody comprising 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, and the pediatric myasthenia gravis is selected from transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome, or any combination thereof. [Brief description of the drawings]

[0008] [Figure 1] FIG. 13 shows the results of modeling designed to predict IgG reduction and MG-ADL improvement with 15 mg / kg and 30 mg / kg q2w maintenance dosing in adult patients with gMG. [Diagram 2] FIG. 1 shows the results of modeling designed to predict IgG reduction and MG-ADL improvement with a 30 mg / kg loading dose in adult patients with gMG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] This application is a continuation of PCT Application No. PCT / US2021 / 058188, filed November 5, 2022, U.S. Provisional Application No. 63 / 110,884, filed November 6, 2020, U.S. Provisional Application No. 63 / 137,972, filed January 15, 2021, U.S. Provisional Application No. 63 / 173,126, filed April 9, 2021, U.S. Provisional Application No. 63 / 173,919, filed April 12, 2021, and U.S. Provisional Application No. 63 / 173,920, filed April 13, 2021. The entirety of each of U.S. Provisional Application No. 63 / 174,423, U.S. Provisional Application No. 63 / 175,440, filed April 15, 2021, U.S. Provisional Application No. 63 / 203,075, filed July 7, 2021, U.S. Provisional Application No. 63 / 203,077, filed July 7, 2021, U.S. Provisional Application No. 63 / 219,155, filed July 7, 2021, and U.S. Provisional Application No. 63 / 266,880, filed January 18, 2022, are incorporated by reference.

[0010] Myasthenia gravis is caused by pathogenic autoantibodies that impair cholinergic transmission at the postsynaptic membrane of the neuromuscular junction, impairing or preventing 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 important for neuromuscular junction formation and agrin-induced AChR clustering, whereas about 7%-8% of patients have neither anti-AChR nor anti-MuSK antibodies and have historically been considered "seronegative". In this latter group, approximately 10% have pathogenic autoantibodies against lipoprotein-related protein receptor 4, an endplate protein that acts as an agrin receptor together with MuSK and is required for AChR clustering and normal neuromuscular junction formation.

[0011] The present disclosure provides embodiments of methods for treating myasthenia gravis and associated symptoms or conditions related thereto. In some embodiments, pediatric subjects with myasthenia gravis are treated with antibodies against human neonatal Fc receptor (FcRn). Anti-FcRn antibodies are useful, for example, for promoting clearance of autoantibodies in pediatric subjects, for suppressing antigen presentation in pediatric subjects, for blocking immune responses, for example, for blocking immune complex-based activation of immune responses in pediatric subjects, or for treating immune diseases (e.g., autoimmune diseases) in pediatric subjects.

[0012] In some embodiments, the anti-FcRn antibody is nipocalimab, which may also be referred to as M281. In some embodiments, the terms "nipocalimab" and "M281" are used interchangeably. Nipocalimab is an antibody against the human neonatal Fc receptor (FcRn). Nipocalimab is described in U.S. Pat. No. 10,676,526, WO 2020 / 023310, WO 2020 / 018910, and WO 2021 / 022249, each of which is incorporated herein by reference in its entirety.

[0013] The term "antibody" as used herein is used in the broadest sense and encompasses a variety of antibody structures, including, but not limited to, monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), scFvs, nanobodies, VHHs, and antibody fragments, so long as they exhibit FcRn antigen-binding activity.

[0014] Furthermore, an antibody or antibody molecule, as that term is used herein, refers to a polypeptide, e.g., an immunoglobulin chain or fragment thereof, that comprises at least one functional immunoglobulin variable domain sequence. Antibody molecules encompass antibodies (e.g., full-length antibodies) and antibody fragments. In some embodiments, an 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 normal immunoglobulin gene fragment recombination processes. 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, include portions of an antibody, e.g., Fab, Fab', F(ab')2, F(ab)2, variable fragments (Fv), domain antibodies (dAb), or single-chain variable fragments (scFv). A functional antibody fragment binds to the same antigen that is recognized by an intact (e.g., full-length) antibody. The term "antibody fragment" or "functional fragment" also includes isolated fragments consisting of the variable regions, such as an "Fv" fragment consisting of the variable regions of the heavy and light chains, or a recombinant single chain polypeptide molecule in which the light and heavy chain variable regions are linked by a peptide linker ("scFv protein"). In some embodiments, an antibody fragment does not include portions of an antibody that do 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, Fab', and F(ab')2 fragments, and single chain variable fragments (scFv).

[0015] Immunoglobulin chains typically exhibit the same general structure, with relatively conserved framework regions (FR) bound by three hypervariable regions, also called complementarity determining regions or CDRs. The CDRs from the two chains of each pair are aligned by the framework regions, allowing binding to a specific epitope. Both the light and heavy chains comprise, from N-terminus to C-terminus, the domains FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. The assignment of amino acids to each domain follows the definition in Kabat, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987 and 1991)). In some embodiments, the antibodies provided herein comprise the same FRs and different CDRs. In some embodiments, the antibodies provided herein comprise the same CDRs and different FRs. In some embodiments, the mutation in the FR is in the heavy chain. In some embodiments, the mutation in the FR is in FR1 of the heavy chain. In some embodiments, the mutation in the FR is in FR2 of the heavy chain. In some embodiments, the mutation in the FR is in FR3 of the heavy chain. In some embodiments, the mutation in the 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 the FR is in FR1 of the light chain. In some embodiments, the mutation in the FR is in FR2 of the light chain. In some embodiments, the mutation in the FR is in FR3 of the light chain. In some embodiments, the mutation in the FR is in FR4 of the light chain. In some embodiments, the mutation in the FR is in the heavy chain and the light chain. In some embodiments, the mutation in the FR is in any one or more of the FRs of the heavy chain and the light chain.

[0016] The term "antibody molecule" also encompasses whole or antigen-binding fragments of domain or single domain antibodies, which may also be referred to as "sdAbs" or "VHHs". Domain antibodies are VHHs that can act as standalone antibody fragments. HOr V L In addition, domain antibodies include heavy chain only antibodies (HCAbs). Domain antibodies also include the CH2 domain of IgG as the basic scaffold onto which the CDR loops are grafted. It may also be generally defined as a polypeptide or protein comprising an amino acid sequence composed of four framework regions interrupted by three complementarity determining regions. This is represented as FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. sdAbs can be produced in camelids such as llamas, but can also be synthetically generated using techniques well known in the art. The numbering of the amino acid residues of sdAbs or polypeptides follows the general numbering of VH domains given by Kabat et al. According to this numbering, FR1 of the sdAb comprises amino acid residues at positions 1 to 30, CDR1 of the sdAb comprises amino acid residues at positions 31 to 36, FR2 of the sdAb comprises amino acid residues at positions 36 to 49, CDR2 of the sdAb comprises amino acid residues at positions 50 to 65, FR3 of the sdAb comprises amino acid residues at positions 66 to 94, CDR3 of the sdAb comprises amino acid residues at positions 95 to 102, and FR4 of the sdAb comprises amino acid residues at positions 103 to 113. Domain antibodies are also described in WO2004041862 and WO2016065323, each of which is incorporated herein by reference.

[0017] In some embodiments, as provided herein, antibody molecules can be monospecific (e.g., monovalent or bivalent), bispecific (e.g., bivalent, trivalent, tetravalent, pentavalent, or hexavalent), trispecific (e.g., trivalent, tetravalent, pentavalent, hexavalent), or of higher specificity (e.g., tetraspecific) and / or of higher valency than hexavalent. An antibody molecule can 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 can be fused together into a single polypeptide.

[0018] As used herein, the term "fused" or "linked" when used in reference to proteins with different domains or heterologous sequences means that the protein domains are part of the same peptide chain linked together either by peptide bonds or other covalent bonds. The domains or sections can be directly linked or fused to each other, or another domain or peptide sequence can be between the two domains or sequences, and such sequences are still considered to be 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 type of peptide linker commonly known to link two domains together. Two peptide sequences are directly linked when they are directly connected to each other, or indirectly linked when there is a linker or other structure that links the two regions. A linker can be directly linked to two different peptide sequences or domains.

[0019] As used herein, the terms "variable region" and "variable domain" refer to the portions of the light and heavy chains of an antibody that contain the amino acid sequences of the complementarity determining regions (CDRs, e.g., CDR L1, CDR L2, CDR L3, CDR H1, CDR H2, and CDR H3) and framework regions (FRs). According to the method used in this disclosure, the amino acid positions assigned to the CDRs and FRs are defined according to Kabat (see Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). Using this numbering system, the actual linear amino acid sequence may contain fewer or additional amino acids corresponding to a shortening of, or insertion into, a CDR (as further defined herein) or FR of the variable region. For example, the heavy chain variable region may include a single inserted residue after residue 52 in CDR H2 (i.e., residue 52a according to Kabat) and inserted residues after residue 82 in the heavy chain FR (e.g., residues 82a, 82b, 82c, etc. according to Kabat). The Kabat numbering of residues can be determined for a given antibody by aligning the sequence of that antibody with the "standard" Kabat numbered sequence at the regions of homology.

[0020] 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 chain 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 CDR H3. Each CDR may comprise 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 (CDR H3) in the heavy chain variable region.

[0021] As used herein, the term "FcRn" refers to the neonatal Fc receptor that binds to the Fc region of IgG antibodies, e.g., IgG1 antibodies. An exemplary FcRn is the human FcRn with UniProt ID number P55899, which is incorporated herein by reference in its entirety. Human FcRn is believed to be involved in maintaining the half-life of IgG by constitutively binding to internalized IgG and transporting it back to the cell surface for IgG recycling.

[0022] 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 an scFv format. In some embodiments, the heavy chain and the light chain are linked by a peptide linker, such as a glycine / serine or glycine / alanine linker.

[0023] In some embodiments, the anti-FcRn antibody is M281. In some embodiments, the anti-FcRn antibody is nipocalimab. In some embodiments, M281 and nipocalimab comprise the same amino acid sequence. In some embodiments, M281 and nipocalimab comprise the same heavy and light chain amino acid sequences. In some embodiments, M281 and nipocalimab comprise the same variable heavy and variable light chain amino acid sequences. As used herein, "M281" and "nipocalimab" refer to the same antibody and can be used interchangeably. In a preferred embodiment, the anti-FcRn antibody is M281.

[0024] In some embodiments, the anti-FcRn antibody can be M281 (nipocalimab). In some embodiments, nipocalimab has the sequence: a light chain comprising, or consisting of, QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1); array: EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTKG PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFP and a heavy chain comprising or consisting of PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 2).

[0025] In some embodiments, the antibody has (a) a light chain sequence that is 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), and CDR L3 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, nipocalimab comprises or consists of a heavy chain comprising or consisting of the sequence shown in SEQ ID NO:2, wherein SEQ ID NO:2 further comprises a C-terminal lysine (K) residue. In some embodiments, SEQ ID NO:2 comprises a C-terminal lysine (K) residue at position 446. In some embodiments, nipocalimab comprises or consists of a heavy chain comprising or consisting of a sequence lacking a C-terminal lysine (K) residue. In some embodiments, nipocalimab comprises or consists of a heavy chain comprising or consisting of a sequence lacking a C-terminal lysine (K) residue at position 446.

[0026] 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 and has one or more amino acid substitutions, which may be A23V or S30R relative to the sequence of SEQ ID NO:2 (according to Kabat numbering). In some embodiments, the antibody light chain comprises an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:1 and has one or more amino acid substitutions.

[0027] In some embodiments, the antibody comprises a light chain variable region comprising an amino acid sequence at least 95%, 97%, 99%, or 100% identical to QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVL (SEQ ID NO: 9). In some embodiments, the light chain variable region contains CDR L1 having the sequence of TGTGSDVGSYNLVS (SEQ ID NO: 3), CDR L2 having the sequence of GDSERPS (SEQ ID NO: 4), and CDR L3 having the sequence of SSYAGSGIYV (SEQ ID NO: 5). In some embodiments, the antibody comprises a heavy chain variable region comprising an amino acid sequence at least 95%, 97%, 99%, or 100% identical to EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSS (SEQ ID NO: 10). In some embodiments, the heavy chain variable region contains CDR H1 having the sequence of TYAMG (SEQ ID NO: 6), CDR H2 having the sequence of SIGASGSQTRYADS (SEQ ID NO: 7), and CDR H3 having the sequence of LAIGDSY (SEQ ID NO: 8).

[0028] The antibody may further contain amino acid substitutions, additions, and / or deletions outside the CDRs (i.e., in the framework regions (FR)). The 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). The amino acid substitutions, additions, and / or deletions may be substitutions, additions, and / or deletions of 8 or less, 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, or 2 or less single amino acids. In some embodiments, the antibody may further comprise any one or more of the following amino acid substitutions: A23V, S30R relative to any one of SEQ ID NOs: 2, 23-26 (according to Kabat numbering).

[0029] In some embodiments, the antibody may contain 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 region is not directly involved in binding of the antibody to its target, but exhibits various effector functions, such as the involvement of the antibody in antibody-dependent cellular cytotoxicity. In some embodiments, the antibody is characterized by reduced (i.e., absent) binding to human complement factor C1q and / or human Fc receptors on natural killer (NK) cells. In some embodiments, the antibody is characterized by reduced (i.e., absent) binding to human FcγRI, FcγRIIA, and / or FcγRIIIA. 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 may 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 mutations L234A / L235A or D265A / N297A. In some embodiments, the anti-FcRn antibody is aglycosylated at position 297. The resulting effectorless antibodies exhibit little binding to complement or Fc receptors (ie, complement C1q binding) and exhibit reduced CDC capabilities.

[0030] In some embodiments, the isolated antibody contains CDR L1 having the sequence TGTGSDVGSYNLVS (SEQ ID NO:3), CDR L2 having the sequence GDSERPS (SEQ ID NO:4), CDR L3 having the sequence SSYAGSGIYV (SEQ ID NO:5), CDR H1 having the sequence NYAMG (SEQ ID NO:12), CDR H2 having the sequence SIGASGAQTRYADS (SEQ ID NO:14), and CDR H3 having the sequence LAIGDSY (SEQ ID NO:8).

[0031] In some embodiments, the isolated antibody contains CDR L1 having the sequence TGTGSDVGSYNLVS (SEQ ID NO: 3), CDR L2 having the sequence GDSERPS (SEQ ID NO: 4), CDR L3 having the sequence SSYAGSGIYV (SEQ ID NO: 5), CDR H1 having the sequence TYAMG (SEQ ID NO: 4), CDR H2 having the sequence SIGASGGQTRYADS (SEQ ID NO: 15), and CDR H3 having the sequence LAIGDSY (SEQ ID NO: 8).

[0032] In some embodiments, the isolated antibody comprises a light chain and a heavy chain, wherein the light chain comprises: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1), The heavy chain is EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYW GQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKK VEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV MHEALHNHYTQKSLSLSPG (SEQ ID NO: 2).

[0033] In some embodiments, the isolated antibody has a heavy chain, wherein the heavy chain comprises a sequence having a sequence as set forth in SEQ ID NO:2, and further comprises a C-terminal lysine (K) residue. In some embodiments, SEQ ID NO:2 comprises a C-terminal lysine (K) residue at position 446.

[0034] In some embodiments the light chain of the isolated antibody is It includes a sequence having at least 90% identity to the sequence of QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1).

[0035] In some embodiments, the heavy chain of the isolated antibody comprises: EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 2).

[0036] 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.

[0037] In some embodiments, the heavy chain of the isolated antibody comprises: EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGSSGAQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL It includes a sequence having at least 90% identity to the sequence of FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 23).

[0038] 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.

[0039] In some embodiments, the heavy chain of the isolated antibody comprises: EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYAMGWVRQAPGKGLEWVSSIGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL It includes a sequence having at least 90% identity to the sequence of FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 24).

[0040] 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.

[0041] In some embodiments, the heavy chain of the isolated antibody comprises: EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYAMGWVRQAPGKGLEWVSSIGASGAQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL It includes a sequence having at least 90% identity to the sequence of FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 25).

[0042] 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.

[0043] In some embodiments, the heavy chain of the isolated antibody comprises: EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGGQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL It includes a sequence having at least 90% identity to the sequence of FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 26).

[0044] 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.

[0045] In some embodiments, the isolated antibody comprises a light chain and a heavy chain, wherein the light chain comprises: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1), The heavy chain is EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYW GQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKK VEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV MHEALHNHYTQKSLSLSPG (SEQ ID NO: 2).

[0046] 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.

[0047] In some embodiments, the isolated antibody comprises a light chain and a heavy chain, wherein the light chain comprises: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1), The heavy chain is EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGSSGAQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTKGPS VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK The sequence includes a sequence having at least 90%, 95%, 98% or 99% identity to the sequence of DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 23).

[0048] 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, the 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.

[0049] In some embodiments, the isolated antibody comprises a light chain and a heavy chain, wherein the light chain comprises: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1), The heavy chain is EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYAMGWVRQAPGKGLEWVSSIGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL It includes a sequence having at least 90% identity to the sequence of FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 24).

[0050] 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, the 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.

[0051] In some embodiments, the isolated antibody comprises a light chain and a heavy chain, wherein the light chain comprises: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1), The heavy chain is EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYAMGWVRQAPGKGLEWVSSIGASGAQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTKGPS VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK The sequence includes a sequence having at least 90%, 95%, 98% or 99% identity to the sequence of DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 25).

[0052] 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, the 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.

[0053] In some embodiments, the isolated antibody comprises a light chain and a heavy chain, wherein the light chain comprises: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1), The heavy chain is EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGGQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSASTKGPS VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK The sequence includes a sequence having at least 90%, 95%, 98% or 99% identity to the sequence of DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 26).

[0054] 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.

[0055] 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. 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, and further comprises a C-terminal lysine (K) residue at position 446 of any one of SEQ ID NOs: 2, 23-26. In some 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.

[0056] 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 one 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 one 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.

[0057] In some embodiments, the isolated antibody further comprises any one or more of the following amino acid substitutions: A23V, S30R (according to EU numbering) relative to the sequence of any one of SEQ ID NOs: 2, 23-26. In some embodiments, the isolated antibody further comprises any one or more of the following amino acid substitutions: A23V, S30R (according to EU numbering) relative to the sequence of any one of SEQ ID NOs: 2, 23-26, and further comprises a C-terminal lysine (K) residue at position 446 of any one of SEQ ID NOs: 2, 23-26.

[0058] In some embodiments, the isolated antibody does not contain a C-terminal lysine at residue 446 compared to the sequence of any one of SEQ ID NO:2.

[0059] In some embodiments, the isolated antibody comprises a light chain and a heavy chain, wherein the light chain comprises: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1), The heavy chain is EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYW GQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKK VEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV MHEALHNHYTQKSLSLSPG (SEQ ID NO: 2).

[0060] In some embodiments, the isolated antibody comprises a light chain and a heavy chain, wherein the light chain comprises: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1), The heavy chain is EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGSSGAQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSA STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 23).

[0061] In some embodiments, the isolated antibody comprises a light chain and a heavy chain, wherein the light chain comprises: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1), The heavy chain is EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYAMGWVRQAPGKGLEWVSSIGASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSA STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 24).

[0062] In some embodiments, the isolated antibody comprises a light chain and a heavy chain, wherein the light chain comprises: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1), The heavy chain is EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYAMGWVRQAPGKGLEWVSSIGASGAQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSA STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 25).

[0063] In some embodiments, the isolated antibody comprises a light chain and a heavy chain, wherein the light chain comprises: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGVSNRFSGSSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1), The heavy chain is EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGGQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSSA STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 26).

[0064] 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 the 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 as necessary to achieve the maximum percent identity (i.e., gaps can be introduced in one or both of the candidate and reference sequences for optimal alignment, and non-homologous sequences can be ignored for comparison purposes). Alignment for purposes of determining percent identity can be achieved using a variety of methods within the skill of the art, e.g., publicly available computer software such as BLAST, ALIGN, or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms required to achieve maximum alignment over the entire length of the sequences being compared. In some embodiments, the percent amino acid (or nucleic acid) sequence identity of a given candidate sequence to, with, or against a given reference sequence (which can alternatively be said to be a given candidate sequence having or comprising a certain percent amino acid (or nucleic acid) sequence identity to, with, or against a given reference sequence) is calculated as follows: 100 x (A / B ratio) A is the number of amino acid (or nucleic acid) residues scored as identical in the alignment of the candidate and reference sequences, and B is the total number of amino acid (or nucleic acid) residues in the reference sequence. In some embodiments where the length of the candidate sequence is not equal to the length of the reference sequence, the percent amino acid (or nucleic acid) sequence identity of the candidate sequence to the reference sequence is not equal to the percent amino acid (or nucleic acid) sequence identity of the reference sequence to the candidate sequence.

[0065] In some embodiments, a reference sequence aligned for comparison with a candidate sequence may show that the candidate sequence exhibits 50% to 100% identity over the entire length of the candidate sequence or over a selected portion of consecutive amino acid (or nucleic acid) residues of the candidate sequence. The length of the candidate sequence aligned for comparison purposes is at least 30% of the length of the reference sequence, such as at least 40%, such as at least 50%, 60%, 70%, 80%, 90%, or 100%. When a position of the candidate sequence is occupied by the same amino acid (or nucleic acid) residue as the corresponding position of the reference sequence, the molecules are identical at that position. The position may be altered by substitution, deletion, or insertion. The substitution, deletion, or insertion may involve a certain number of amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more). When describing a substitution, deletion, or insertion of up to "n" amino acids, this means that the substitution, deletion, or insertion includes, 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 can include a percentage of the total sequence (e.g., 1%, 5%, 10%, 15%, 20% or more), where the number of substitutions, deletions, or insertions changes 5%, 10%, 15%, 20% or more of the amino acids in the total sequence.

[0066] In some embodiments, the Fc domain of the antibody is not fucosylated. In some embodiments of all the methods described herein, the Fc domain of the antibody is not glycosylated. In some embodiments of all the methods described herein, the antibody lacks effector function. In some embodiments of all the methods described herein, the antibody is an IgG1 antibody.

[0067] In some embodiments, the anti-FcRn antibody is nipocalimab, RVT-1401 (HL161), rozanolixizumab (UCB7665), ALXN1830, ABY-039, or efgartigimod. RVT-1401 (also referred to as HL161BKN) is described in WO2020097099, rozanolixizumab is described in WO2014019727, and efgartigimod (ARGX-113) is further described in WO2015100299, each of which is incorporated herein by reference in its entirety. In some embodiments, the anti-FcRn antibody is a biosimilar of any of the anti-FcRn antibodies provided herein.

[0068] In some embodiments, the methods described herein include administering an anti-FcRn antibody to a pediatric subject or patient. The terms "pediatric subject" or "pediatric patient" can be used interchangeably. In some embodiments, the pediatric subject is between 2 and under 18 years old. In some embodiments, the pediatric subject is between 2 and under 12 years old. In some embodiments, the pediatric subject is under 12 years old to under 18 years old. In some embodiments, the pediatric subject is an adolescent, defined as under 18 years old or between 16 and 17 years old. In some embodiments, the pediatric subject is a teenager, defined as between 12 and 15 years old. In some embodiments, the pediatric subject is a child, defined as between 2 and 11 years old.

[0069] Myasthenia gravis in the pediatric population is classified into three categories: 1) transient neonatal myasthenia gravis, 2) juvenile myasthenia gravis (juvenile MG), and 3) congenital myasthenic syndrome (CMS). Juvenile MG is an autoimmune disorder in which autoantibodies against structural components of the neuromuscular junction disrupt neuromuscular transmission. In some embodiments, the methods described herein include administering an anti-FcRn antibody to a pediatric subject diagnosed with transient neonatal myasthenia gravis. In some embodiments, the methods described herein include administering an anti-FcRn antibody to a pediatric subject diagnosed with juvenile myasthenia gravis (juvenile MG). In some embodiments, the methods described herein include administering an anti-FcRn antibody to a pediatric subject diagnosed with congenital myasthenic syndrome (CMS).

[0070] In some embodiments, methods of treating pediatric myasthenia gravis in a pediatric patient in need of treatment are provided. In some embodiments, the method comprises administering an initial loading dose of about 30 mg / kg to about 60 mg / kg of an anti-FcRn antibody, followed by a maintenance dose of about 15 mg / kg to about 30 mg / kg of an anti-FcRn antibody, wherein the anti-FcRn antibody comprises a heavy chain comprising an HCDR1 of SEQ ID NO: 6, an HCDR2 of SEQ ID NO: 7, and an HCDR3 of SEQ ID NO: 8, and a light chain comprising an LCDR1 of SEQ ID NO: 3, an LCDR2 of SEQ ID NO: 4, and an LCDR3 of SEQ ID NO: 5, wherein the administration reduces serum IgG in 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 transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome, or any combination thereof.

[0071] 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 30 mg / kg to about 60 mg / kg of an anti-FcRn antibody, followed by a maintenance dose of about 15 mg / kg to about 30 mg / kg of an anti-FcRn antibody, wherein the anti-FcRn antibody comprises a heavy chain comprising an HCDR1 of SEQ ID NO: 6, an HCDR2 of SEQ ID NO: 7, and an HCDR3 of SEQ ID NO: 8, and a light chain comprising an LCDR1 of SEQ ID NO: 3, an LCDR2 of SEQ ID NO: 4, and an LCDR3 of SEQ ID NO: 5, wherein the administration reduces serum IgG in 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 the pediatric myasthenia gravis is transient neonatal myasthenia gravis.

[0072] In some embodiments, methods are provided for treating pediatric myasthenia gravis in a pediatric patient in need of such treatment. In some embodiments, the methods include administering an initial loading dose of about 30 mg / kg to about 60 mg / kg of an anti-FcRn antibody, followed by a maintenance dose of about 15 mg / kg to about 30 mg / kg of an anti-FcRn antibody, wherein the anti-FcRn antibody comprises a heavy chain comprising an HCDR1 of SEQ ID NO: 6, an HCDR2 of SEQ ID NO: 7, and an HCDR3 of SEQ ID NO: 8, and a light chain comprising an LCDR1 of SEQ ID NO: 3, an LCDR2 of SEQ ID NO: 4, and an LCDR3 of SEQ ID NO: 5, wherein the administration reduces serum IgG in 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.

[0073] In some embodiments, methods are provided for treating pediatric myasthenia gravis in a pediatric patient in need of such treatment. In some embodiments, the methods include administering an initial loading dose of about 30 mg / kg to about 60 mg / kg of an anti-FcRn antibody, followed by a maintenance dose of about 15 mg / kg to about 30 mg / kg of an anti-FcRn antibody, wherein the anti-FcRn antibody comprises a heavy chain comprising an HCDR1 of SEQ ID NO: 6, an HCDR2 of SEQ ID NO: 7, and an HCDR3 of SEQ ID NO: 8, and a light chain comprising an LCDR1 of SEQ ID NO: 3, an LCDR2 of SEQ ID NO: 4, and an LCDR3 of SEQ ID NO: 5, wherein the administration reduces serum IgG in 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.

[0074] In some embodiments, the antibody is administered as part of a pharmaceutical composition comprising 5 to 60 mg / ml of antibody. In some embodiments, the antibody is administered at an initial dose that is 60 mg / kg. In some embodiments, the antibody is administered at an initial dose that is 30 mg / kg. In some embodiments, the antibody is administered at an initial loading dose that is 60 mg / kg. In some embodiments, the antibody is administered at an initial loading dose that is 30 mg / kg. In some embodiments, the antibody is administered at a dose of about 5 mg / kg to about 60 mg / kg, about 5 mg / kg to about 15 mg / kg, about 15 mg / kg to about 60 mg / kg, or about 30 mg / kg to about 60 mg / kg. In some embodiments, the antibody is administered at a dose of about 5 mg / kg, about 15 mg / kg, about 30 mg / kg, about 45 mg / kg, or about 60 mg / kg. In some embodiments, the antibody is administered at a dose of exactly or about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 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 5 mg / kg to about 60 mg / kg, about 5 mg / kg to about 15 mg / kg, about 15 mg / kg to about 60 mg / kg, or about 30 mg / 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 5 mg / kg to about 60 mg / kg, about 5 mg / kg to about 15 mg / kg, about 15 mg / kg to about 60 mg / kg, or about 30 mg / kg to about 60 mg / kg. In some embodiments, the maintenance dose is administered at a dose of about 5 mg / kg, about 15 mg / kg, about 30 mg / kg, about 45 mg / kg, or about 60 mg / kg. In some embodiments, the maintenance dose is administered at a dose of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 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 30 mg / kg and a maintenance dose of about 15 mg / kg. In some embodiments, the loading dose is administered at a dose of 30 mg / kg and a maintenance dose of 15 mg / kg.

[0075] In some embodiments, the antibody is administered weekly, every two weeks, or monthly. In some embodiments, the initial dose is different from the weekly or every two weeks dose. In some embodiments, the dose is the same each time it is administered. In some embodiments, the antibody is administered at least weekly, every two weeks, every three weeks, or every four weeks (i.e., once a month). In some embodiments, the first infusion of the antibody is administered at a loading dose of about 60 mg / kg, and the second infusion of the antibody is administered weekly at a maintenance dose of about 15 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 30 mg / kg, and the second infusion of the antibody is administered weekly at a maintenance dose of about 15 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 60 mg / kg, and the second infusion of the antibody is administered every two weeks at a maintenance dose of about 15 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 30 mg / kg and the second infusion of the antibody is administered every two weeks at a maintenance dose of about 15 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 60 mg / kg and the second infusion of the antibody is administered at a maintenance dose of about 15 mg / kg every three weeks. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 30 mg / kg and the second infusion of the antibody is administered at a maintenance dose of about 15 mg / kg every three weeks. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 60 mg / kg and the second infusion of the antibody is administered at a maintenance dose of about 15 mg / kg every four weeks. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 30 mg / kg and the second infusion of the antibody is administered at a maintenance dose of about 15 mg / kg every four weeks. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 60 mg / kg and the second infusion of the antibody is administered monthly at a maintenance dose of about 15 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 30 mg / kg and the second infusion of the antibody is administered monthly at a maintenance dose of about 15 mg / kg.

[0076] In some embodiments, the first infusion of the antibody is administered at a loading dose of about 5-60 mg / kg and the second infusion of the antibody is administered weekly at a maintenance dose of about 5-60 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 5-60 mg / kg and the second infusion of the antibody is administered every two weeks at a maintenance dose of about 5-60 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 5-60 mg / kg and the second infusion of the antibody is administered every three weeks at a maintenance dose of about 5-60 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 5-60 mg / kg and the second infusion of the antibody is administered every four weeks at a maintenance dose of about 5-60 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 5-60 mg / kg and the second infusion of the antibody is administered monthly at a maintenance dose of about 5-60 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 5-30 mg / kg and the second infusion of the antibody is administered weekly at a maintenance dose of about 5-30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 5-30 mg / kg and the second infusion of the antibody is administered every two weeks at a maintenance dose of about 5-30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 5-30 mg / kg and the second infusion of the antibody is administered every three weeks at a maintenance dose of about 5-30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 5-30 mg / kg and the second infusion of the antibody is administered every four weeks at a maintenance dose of about 5-30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 5-30 mg / kg and the second infusion of the antibody is administered monthly at a maintenance dose of about 5-30 mg / kg. In some embodiments, a first infusion of antibody is administered at a loading dose of about 15-30 mg / kg and a second infusion of antibody is administered weekly at a maintenance dose of about 15-30 mg / kg. In some embodiments, a first infusion of antibody is administered at a loading dose of about 15-30 mg / kg and a second infusion of antibody is administered every two weeks at a maintenance dose of about 15-30 mg / kg.In some embodiments, the first infusion of the antibody is administered at a loading dose of about 15-30 mg / kg and the second infusion of the antibody is administered every 3 weeks at a maintenance dose of about 15-30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 15-30 mg / kg and the second infusion of the antibody is administered every 4 weeks at a maintenance dose of about 15-30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 15-30 mg / kg and the second infusion of the antibody is administered monthly at a maintenance dose of about 15-30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 60 mg / kg and the second infusion of the antibody is administered weekly at a maintenance dose of about 30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 60 mg / kg and the second infusion of the antibody is administered every 2 weeks at a maintenance dose of about 30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 60 mg / kg and the second infusion of the antibody is administered every three weeks at a maintenance dose of about 30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 60 mg / kg and the second infusion of the antibody is administered every four weeks at a maintenance dose of about 30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 60 mg / kg and the second infusion of the antibody is administered monthly at a maintenance dose of about 30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 30 mg / kg and the second infusion of the antibody is administered weekly at a maintenance dose of about 30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 30 mg / kg and the second infusion of the antibody is administered every two weeks at a maintenance dose of about 30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 30 mg / kg and the second infusion of the antibody is administered every three weeks at a maintenance dose of about 30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 30 mg / kg and the second infusion of the antibody is administered every four weeks at a maintenance dose of about 30 mg / kg. In some embodiments, the first infusion of the antibody is administered at a loading dose of about 30 mg / kg and the second infusion of the antibody is administered monthly at a maintenance dose of about 30 mg / kg.In some embodiments, the additional injections are administered at a maintenance dose of about 5-60 mg / kg. In some embodiments, the additional injections are administered at a maintenance dose of about 5-30 mg / kg. In some embodiments, the additional injections are administered at a maintenance dose of about 15-30 mg / kg. In some embodiments, the additional injections are administered at a maintenance dose of about 15 mg / kg. In some embodiments, the additional injections are administered at a maintenance dose of about 30 mg / kg. In some embodiments, the injections (including the first, second, and / or additional) are administered every two weeks, every three weeks, every four weeks, or monthly. In some embodiments, the method includes an initial (loading) dose followed by a biweekly (e.g., every two weeks) maintenance dose. In some embodiments, the method includes an initial (loading) dose followed by a maintenance dose every three weeks. In some embodiments, the method includes an initial (loading) dose followed by a maintenance dose every four weeks. In some embodiments, the method includes an initial (loading) dose followed by a monthly maintenance dose. In some embodiments, the initial dose is higher than the biweekly maintenance dose. In some embodiments, the initial dose is the same as the biweekly maintenance dose.

[0077] In some embodiments, administration of the antibody or pharmaceutical composition occurs over a period of about 30 to 90 minutes. In some embodiments, administration occurs over a period of about 15 to 60 minutes. In some embodiments, administration occurs within about 15 to about 30 minutes. In some embodiments, administration occurs within about 15 to about 45 minutes. In some embodiments, administration occurs within about 15 to about 90 minutes. In some embodiments, administration occurs within about 15 to about 120 minutes. In some embodiments, administration occurs within about 15 minutes, about 30 minutes, about 45 minutes, about 60 minutes, about 90 minutes, or about 120 minutes.

[0078] 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 some embodiments, the composition is administered intravenously. In some embodiments, 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 autoinjector. In some embodiments, the composition is administered using a patch pump injector. In some embodiments, the composition is administered using a wearable injector. In some embodiments, the composition is administered using a Sorrel™ pump. In some embodiments, the composition is administered using a pump such as those in U.S. Pat. No. 9,943,642, which is incorporated herein in its entirety.

[0079] In certain embodiments, a method of treating generalized myasthenia gravis in a pediatric subject in need of treatment comprises administering a therapeutically effective amount of nipocalimab intravenously to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is 5-60 mg / kg. In certain embodiments, a method of treating generalized myasthenia gravis in a pediatric subject in need of treatment comprises administering a therapeutically effective amount of nipocalimab intravenously to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is 5-30 mg / kg. In certain embodiments, a method of treating generalized myasthenia gravis in a pediatric subject in need of treatment comprises administering a therapeutically effective amount of nipocalimab intravenously to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is 15-30 mg / kg. In certain embodiments, a method of treating generalized myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, wherein the nipocalimab is administered as a loading dose of 5-60 mg / kg followed by a maintenance dose of 5-60 mg / kg every two weeks. In certain embodiments, a method of treating generalized myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 5-30 mg / kg, followed by a maintenance dose of 5-30 mg / kg every two weeks. In certain embodiments, a method of treating generalized myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 15-30 mg / kg, followed by a maintenance dose of 15-30 mg / kg every two weeks. In certain embodiments, a method of treating generalized myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 5-60 mg / kg, followed by a maintenance dose of 5-60 mg / kg every four weeks. In certain embodiments, a method of treating generalized myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nipocalimab to the pediatric subject, wherein nipocalimab is administered as a loading dose of 5-30 mg / kg, followed by a maintenance dose of 5-30 mg / kg every four weeks.In certain embodiments, a method of treating generalized myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering nipocalimab to the pediatric subject, wherein nipocalimab is administered as a loading dose of 15-30 mg / kg, followed by a maintenance dose of 15-30 mg / kg every 4 weeks. In certain embodiments, a method of treating generalized myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is 30 mg / kg. In certain embodiments, a method of treating generalized myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is 15 mg / kg. In certain embodiments, a method of treating generalized myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 30 mg / kg followed by a maintenance dose of 15 mg / kg every two weeks. In certain embodiments, a method of treating generalized myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 30 mg / kg followed by a maintenance dose of 30 mg / kg every four weeks.

[0080] In certain embodiments, a method of treating transient neonatal myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is between 5 and 60 mg / kg. In certain embodiments, a method of treating transient neonatal myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is between 5 and 30 mg / kg. In certain embodiments, a method of treating transient neonatal myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is between 15 and 30 mg / kg. In certain embodiments, a method of treating transient neonatal myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 5-60 mg / kg, followed by a maintenance dose of 5-60 mg / kg every two weeks. In certain embodiments, a method of treating transient neonatal myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 5-30 mg / kg, followed by a maintenance dose of 5-30 mg / kg every two weeks. In certain embodiments, a method of treating transient neonatal myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 15-30 mg / kg, followed by a maintenance dose of 15-30 mg / kg every two weeks. In certain embodiments, a method of treating transient neonatal myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering nipocalimab to the pediatric subject, where nipocalimab is administered as a loading dose of 5-60 mg / kg followed by a maintenance dose of 5-60 mg / kg every four weeks. In certain embodiments, a method of treating transient neonatal myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering nipocalimab to the pediatric subject, where nipocalimab is administered as a loading dose of 5-30 mg / kg followed by a maintenance dose of 5-30 mg / kg every four weeks.In certain embodiments, a method of treating transient neonatal myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering nipocalimab to the pediatric subject, where nipocalimab is administered as a loading dose of 15-30 mg / kg followed by a maintenance dose of 15-30 mg / kg every four weeks. In certain embodiments, a method of treating transient neonatal myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, where the therapeutically effective amount of nipocalimab is 30 mg / kg. In certain embodiments, a method of treating transient neonatal myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, where the therapeutically effective amount of nipocalimab is 15 mg / kg. In certain embodiments, a method of treating transient neonatal myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 30 mg / kg followed by a maintenance dose of 15 mg / kg every two weeks. In certain embodiments, a method of treating transient neonatal myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 30 mg / kg followed by a maintenance dose of 30 mg / kg every four weeks.

[0081] In certain embodiments, a method of treating juvenile myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is 5-60 mg / kg. In certain embodiments, a method of treating juvenile myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is 5-30 mg / kg. In certain embodiments, a method of treating juvenile myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is 15-30 mg / kg. In certain embodiments, a method of treating juvenile myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering nipocalimab to the pediatric subject, wherein the nipocalimab is administered as a loading dose of 5-60 mg / kg followed by a maintenance dose of 5-60 mg / kg every two weeks. In certain embodiments, a method of treating juvenile myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 5-30 mg / kg, followed by a maintenance dose of 5-30 mg / kg every two weeks. In certain embodiments, a method of treating juvenile myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 15-30 mg / kg, followed by a maintenance dose of 15-30 mg / kg every two weeks. In certain embodiments, a method of treating juvenile myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 5-60 mg / kg, followed by a maintenance dose of 5-60 mg / kg every four weeks. In certain embodiments, a method of treating juvenile myasthenia gravis in a pediatric subject in need thereof comprises intravenously administering nipocalimab to the pediatric subject, wherein nipocalimab is administered as a loading dose of 5-30 mg / kg followed by a maintenance dose of 5-30 mg / kg every four weeks.In certain embodiments, a method of treating juvenile myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering nipocalimab to the pediatric subject, where nipocalimab is administered as a loading dose of 15-30 mg / kg followed by a maintenance dose of 15-30 mg / kg every four weeks. In certain embodiments, a method of treating juvenile myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, where the therapeutically effective amount of nipocalimab is 30 mg / kg. In certain embodiments, a method of treating juvenile myasthenia gravis in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, where the therapeutically effective amount of nipocalimab is 15 mg / kg. In certain embodiments, a method of treating juvenile myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 30 mg / kg followed by a maintenance dose of 15 mg / kg every two weeks. In certain embodiments, a method of treating juvenile myasthenia gravis in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 30 mg / kg followed by a maintenance dose of 30 mg / kg every four weeks.

[0082] In certain embodiments, a method of treating congenital myasthenic syndrome (CMS) in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is between 5 and 60 mg / kg. In certain embodiments, a method of treating congenital myasthenic syndrome (CMS) in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is between 5 and 30 mg / kg. In certain embodiments, a method of treating congenital myasthenic syndrome (CMS) in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is between 15 and 30 mg / kg. In certain embodiments, a method of treating congenital myasthenic syndrome (CMS) in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 5-60 mg / kg, followed by a maintenance dose of 5-60 mg / kg every two weeks. In certain embodiments, a method of treating congenital myasthenic syndrome (CMS) in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 5-30 mg / kg, followed by a maintenance dose of 5-30 mg / kg every two weeks. In certain embodiments, a method of treating congenital myasthenic syndrome (CMS) in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 15-30 mg / kg, followed by a maintenance dose of 15-30 mg / kg every two weeks. In certain embodiments, a method of treating congenital myasthenic syndrome (CMS) in a pediatric subject in need of treatment comprises intravenously administering nipocalimab to the pediatric subject, where nipocalimab is administered as a loading dose of 5-60 mg / kg, followed by a maintenance dose of 5-60 mg / kg every four weeks. In certain embodiments, a method of treating congenital myasthenic syndrome (CMS) in a pediatric subject in need of treatment comprises intravenously administering nipocalimab to the pediatric subject, where nipocalimab is administered as a loading dose of 5-30 mg / kg, followed by a maintenance dose of 5-30 mg / kg every four weeks.In certain embodiments, a method of treating congenital myasthenic syndrome (CMS) in a pediatric subject in need of treatment comprises intravenously administering nipocalimab to the pediatric subject, where nipocalimab is administered as a loading dose of 15-30 mg / kg followed by a maintenance dose of 15-30 mg / kg every 4 weeks. In certain embodiments, a method of treating congenital myasthenic syndrome (CMS) in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, where the therapeutically effective amount of nipocalimab is 30 mg / kg. In certain embodiments, a method of treating congenital myasthenic syndrome (CMS) in a pediatric subject in need of treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, where the therapeutically effective amount of nipocalimab is 15 mg / kg. In certain embodiments, a method of treating congenital myasthenic syndrome (CMS) in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 30 mg / kg, followed by a maintenance dose of 15 mg / kg every two weeks. In certain embodiments, a method of treating congenital myasthenic syndrome (CMS) in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, where nipocalimab is administered as a loading dose of 30 mg / kg, followed by a maintenance dose of 30 mg / kg every four weeks.

[0083] In certain embodiments, a method of treating transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, in a pediatric subject in need of such treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is 5-60 mg / kg. In certain embodiments, a method of treating transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, in a pediatric subject in need of such treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is 5-30 mg / kg. In certain embodiments, a method of treating transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, in a pediatric subject in need of such treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is 15-30 mg / kg. In certain embodiments, a method of treating transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, in a pediatric subject in need of such treatment comprises intravenously administering nipocalimab to the pediatric subject, wherein nipocalimab is administered as a loading dose of 5-60 mg / kg followed by a maintenance dose of 5-60 mg / kg every two weeks. In certain embodiments, a method of treating transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, in a pediatric subject in need of such treatment comprises intravenously administering nipocalimab to the pediatric subject, where nipocalimab is administered as a loading dose of 5-30 mg / kg, followed by a maintenance dose of 5-30 mg / kg every two weeks. In certain embodiments, a method of treating transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, in a pediatric subject in need of such treatment comprises intravenously administering nipocalimab to the pediatric subject, where nipocalimab is administered as a loading dose of 15-30 mg / kg, followed by a maintenance dose of 15-30 mg / kg every two weeks.In certain embodiments, a method of treating transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, in a pediatric subject in need of such treatment comprises intravenously administering nipocalimab to the pediatric subject, wherein nipocalimab is administered as a loading dose of 5-60 mg / kg followed by a maintenance dose of 5-60 mg / kg every four weeks. In certain embodiments, a method of treating transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, in a pediatric subject in need of such treatment comprises intravenously administering nipocalimab to the pediatric subject, wherein nipocalimab is administered as a loading dose of 5-30 mg / kg followed by a maintenance dose of 5-30 mg / kg every four weeks. In certain embodiments, a method of treating transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, in a pediatric subject in need of such treatment comprises intravenously administering nipocalimab to the pediatric subject, wherein nipocalimab is administered as a loading dose of 15-30 mg / kg followed by a maintenance dose of 15-30 mg / kg every four weeks. In certain embodiments, a method of treating transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, in a pediatric subject in need of such treatment comprises intravenously administering a therapeutically effective amount of nipocalimab to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is 30 mg / kg. In certain embodiments, a method of treating transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in a pediatric subject in need of treatment comprises administering a therapeutically effective amount of nipocalimab intravenously to the pediatric subject, wherein the therapeutically effective amount of nipocalimab is 15 mg / kg. In certain embodiments, a method of treating transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in a pediatric subject in need of treatment comprises administering nipocalimab intravenously to the pediatric subject, wherein nipocalimab is administered as a loading dose of 30 mg / kg followed by a maintenance dose of 15 mg / kg every two weeks.In certain embodiments, a method of treating transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, in a pediatric subject in need thereof comprises intravenously administering nipocalimab to the pediatric subject, wherein nipocalimab is administered as a loading dose of 30 mg / kg followed by a maintenance dose of 30 mg / kg every 4 weeks.

[0084] In some embodiments, the pharmaceutical composition comprises one or more of sodium phosphate, sodium chloride, trehalose, or polysorbate.

[0085] As used herein, the term "pharmaceutical composition" refers to a pharmaceutical formulation or preparation containing an active ingredient and one or more excipients and diluents to make the active ingredient suitable for the method of administration. The pharmaceutical composition of the present disclosure includes pharma- ceutical acceptable ingredients that are 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.

[0086] In some embodiments, the pharmaceutical composition of the present invention containing an anti-FcRn antibody as a therapeutic protein may be formulated for intravenous, parenteral, subcutaneous, intramuscular, intraarterial, intrathecal, or intraperitoneal administration. In some embodiments, the pharmaceutical composition may also be formulated for or administered via oral, nasal, spray, aerosol, rectal, or vaginal administration. For injectable preparations, a variety of effective pharmaceutical carriers are known in the art.

[0087] As used herein, the term "pharmaceutical acceptable carrier" refers to an excipient or diluent in a pharmaceutical composition. A pharmaceutical acceptable carrier must be compatible with other ingredients of the formulation and not harmful to the recipient. In the present disclosure, a pharmaceutical acceptable carrier must provide the Fc construct with suitable pharmaceutical stability. The nature of the carrier will vary depending on the mode of administration. For example, for intravenous administration, an aqueous solution carrier is generally used, while for oral administration, a solid carrier is preferred.

[0088] As used herein, the term "therapeutically effective amount" refers to an amount, e.g., a pharmaceutical dose, effective in inducing a desired biological effect in a pediatric subject or patient, or in treating a patient having a condition or disorder described herein. It is also understood that, as used herein, a "therapeutically effective amount" may be interpreted as an amount that provides the desired therapeutic effect, either alone or in combination with other therapeutic agents, taken at a time, or taken in any dosage or route.

[0089] As used herein, the term "not more than" refers to an amount of. It may be an integer amount. For example, up to two substitutions can refer to 0, 1, or 2 substitutions.

[0090] As used herein, the term "treatment" or "treating" refers to reducing, decreasing, reducing the risk of, or reducing the side effects of a particular disease or condition. The reducing, decreasing, reducing the risk, or reducing the side effects is compared to a pediatric subject not receiving the treatment, e.g., a control, baseline, or known control level or measurement.

[0091] Thus, in some embodiments, methods are provided for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof in a pediatric subject. In some embodiments, the myasthenia gravis is generalized myasthenia gravis. In some embodiments, the myasthenia gravis is transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof. In some embodiments, the myasthenia gravis is transient 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 with a suboptimal response to a stable treatment for gMG, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof. In some embodiments, the stable treatment for gMG, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, comprises an acetylcholinesterase inhibitor, a glucocorticosteroid, and an immunosuppressant. In some embodiments, the immunosuppressant is selected from azathioprine, mycophenolate mofetil / mycophenolic acid, methotrexate, cyclosporine, tacrolimus, and cyclophosphamide. In some embodiments, the method comprises administering a pharmaceutical composition comprising administering an anti-FcRn antibody to the pediatric subject. In some embodiments, the anti-FcRn antibody is nipocalimab, RVT-1401 (HL161), rozanolixizumab (UCB7665), ALXN1830, ABY-039, or efgartigimod. In some embodiments, the antibody is nipocalimab. In some embodiments, the anti-FcRn antibody is as provided herein.

[0092] In some embodiments, a pediatric subject being treated for myasthenia gravis shows improvement in one or more of the following assays, scores, or criteria that can be used to assess the improvement or condition of a pediatric subject with myasthenia gravis: In some embodiments, the myasthenia gravis is transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof. In some embodiments, the myasthenia gravis is transient 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-Activities of Daily Living (MG-ADL) score, Quantitative Myasthenia Gravis (QMG) score, European Quality of Life 5-Dimension Youth (EQ-5D-Y) tool, Myasthenia Gravis Quality of Life (MG-QoL15r) score, Neuro-QoL Fatigue score, Pediatric Quality of Life Inventory (PedsQL), EQ-5D-5L score, EQ-5D-5Y score, Myasthenia Gravis Foundation of America (MGFA) scale, patient global impression of severity (PGI-S) score, and patient global impression of change (PGI-C) score.

[0093] In some embodiments, a pediatric subject being treated for myasthenia gravis, or transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, has or exhibits a reduction in one or more immunoglobulin isotypes or total IgG. In some embodiments, a subject being treated for myasthenia gravis has or exhibits a reduction in one or more immunoglobulin isotypes or total IgG. In some embodiments, a subject being treated for myasthenia gravis or moderately to severely active myasthenia gravis has or exhibits a reduction in one or more immunoglobulin isotypes or total IgG. In some embodiments, a subject being treated for juvenile myasthenia gravis has or exhibits a reduction in one or more immunoglobulin isotypes or total IgG. In some embodiments, a subject being treated for transient neonatal myasthenia gravis has or exhibits a reduction in one or more immunoglobulin isotypes or total IgG. In some embodiments, a subject being treated for congenital myasthenia gravis syndrome (CMS) has or exhibits a reduction 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%, 5-20%, 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 reduced immunoglobulin isotype 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 IgG1. 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 an 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 IgG2. In some embodiments, administration of an anti-FcRn antibody reduces serum IgG2 in a patient by at least 90% of baseline. In some embodiments, administration of an anti-FcRn antibody reduces serum IgG2 in a patient by at least 80% of baseline. In some embodiments, administration of an anti-FcRn antibody reduces serum IgG2 in a patient by at least 70% of baseline. In some embodiments, administration of an 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 IgG3. In some embodiments, administration of an anti-FcRn antibody reduces serum IgG3 in a patient by at least 90% of baseline. In some embodiments, administration of an anti-FcRn antibody reduces serum IgG3 in a patient by at least 80% of baseline. In some embodiments, administration of an anti-FcRn antibody reduces serum IgG3 in a 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 IgG4. 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.

[0094] In some embodiments, pediatric subjects being treated for myasthenia gravis have or exhibit reduced autoantibodies. In some embodiments, subjects being treated for myasthenia gravis have or exhibit reduced autoantibodies. In some embodiments, subjects being treated for transient neonatal myasthenia gravis have or exhibit reduced autoantibodies. In some embodiments, subjects being treated for juvenile myasthenia gravis have or exhibit reduced autoantibodies. In some embodiments, subjects being treated for congenital myasthenia gravis syndrome (CMS) have or exhibit reduced autoantibodies. In some embodiments, the reduction is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1-20%, 5-20%, 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 (LRP4), anti-agrin, anti-titin, anti-Kv1.4, anti-ryanodine receptor, anti-collagen Q, and anti-cortactin. In some embodiments, the autoantibody is an anti-AChR or anti-MuSK antibody. In some embodiments, administration of an anti-FcRn antibody reduces anti-AChR antibodies by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 50%, or at least 25% of baseline anti-AChR antibodies. In some embodiments, administration of an anti-FcRn antibody reduces anti-AChR antibodies by at least 95% of baseline anti-AChR antibodies. In some embodiments, administration of an anti-FcRn antibody reduces anti-AChR antibodies by at least 90% of baseline anti-AChR antibodies. In some embodiments, administration of an anti-FcRn antibody reduces anti-AChR antibodies by at least 85% of baseline anti-AChR antibodies. In some embodiments, administration of an anti-FcRn antibody reduces anti-AChR antibodies by at least 80% of baseline anti-AChR antibodies.In some embodiments, administration of anti-FcRn antibody reduces anti-AChR antibody by at least 75% of baseline anti-AChR antibody. In some embodiments, administration of anti-FcRn antibody reduces anti-AChR antibody by at least 50% of baseline anti-AChR antibody. In some embodiments, administration of anti-FcRn antibody reduces anti-AChR antibody by at least 25% of baseline anti-AChR antibody. In some embodiments, administration of anti-FcRn antibody reduces 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 baseline anti-MuSK antibody. In some embodiments, administration of anti-FcRn antibody reduces anti-MuSK antibody by at least 95% of baseline anti-MuSK antibody. In some embodiments, administration of anti-FcRn antibody reduces anti-MuSK antibody by at least 90% of baseline anti-MuSK antibody. In some embodiments, administration of the anti-FcRn antibody reduces anti-MuSK antibody by at least 85% of baseline anti-MuSK antibody. In some embodiments, administration of the anti-FcRn antibody reduces anti-MuSK antibody by at least 80% of baseline anti-MuSK antibody. In some embodiments, administration of the anti-FcRn antibody reduces anti-MuSK antibody by at least 75% of baseline anti-MuSK antibody. In some embodiments, administration of the anti-FcRn antibody reduces anti-MuSK antibody by at least 50% of baseline anti-MuSK antibody. In some embodiments, administration of the anti-FcRn antibody reduces anti-MuSK antibody by at least 25% of baseline anti-MuSK antibody. In some embodiments, administration of anti-FcRn antibodies reduces anti-AChR antibodies by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 50%, or at least 25% of baseline anti-AChR antibodies and reduces anti-MuSK antibodies by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 50%, or at least 25% of baseline anti-MuSK antibodies.

[0095] In some embodiments, administration of an anti-FcRn antibody reduces serum albumin by up to 18%, up to 16%, up to 14%, up to 12%, up to 10%, up to 8%, up to 6%, up to 4%, or up to 2% of baseline serum albumin. In some embodiments, administration of an anti-FcRn antibody reduces serum albumin by up to 18% of baseline serum albumin. In some embodiments, administration of an anti-FcRn antibody reduces serum albumin by up to 16% of baseline serum albumin. In some embodiments, administration of an anti-FcRn antibody reduces serum albumin by up to 14% of baseline serum albumin. In some embodiments, administration of an anti-FcRn antibody reduces serum albumin by up to 12% of baseline serum albumin. In some embodiments, administration of an anti-FcRn antibody reduces serum albumin by up to 10% of baseline serum albumin. In some embodiments, administration of an anti-FcRn antibody reduces serum albumin by up to 8% of baseline serum albumin. In some embodiments, administration of an anti-FcRn antibody reduces serum albumin by up to 6% of baseline serum albumin. In some embodiments, administration of an anti-FcRn antibody reduces serum albumin by up to 4% of baseline serum albumin. In some embodiments, administration of an anti-FcRn antibody reduces serum albumin by up to 2% of baseline serum albumin.

[0096] In some embodiments, the pediatric subject is also treated with an additional therapeutic agent in addition to M281. In some embodiments, the additional therapeutic agent is an acetylcholinesterase inhibitor, pyridostigmine, pyridostigmine bromide (Mestinon), neostigmine, prednisone, azathioprine (Imuran), mycophenylate mofetil (CellCept), tacrolimus (Prograf), methotrexate, cyclosporine (Sandimmune, 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) M281.

[0097] In some embodiments, the method comprises administering a pharmaceutical composition comprising administering an anti-FcRn antibody to a pediatric subject. In some embodiments, the anti-FcRn antibody is nipocalimab, RVT-1401 (HL161), rozanolixizumab (UCB7665), ALXN1830, ABY-039, or efgartigimod. In some embodiments, the antibody is nipocalimab. In some embodiments, the 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 nipocalimab.

[0098] In some embodiments, administration of an anti-FcRn antibody to a pediatric subject with myasthenia gravis treats or ameliorates ocular myasthenia, ptosis, difficulty chewing, dysphagia, inability to speak, dysphonia, difficulty breathing, inability to keep mouth closed, appearance of sadness or drowsiness, difficulty holding head upright, double vision, inability to speak, difficulty swallowing, changes in facial expression, shortness of breath, arm weakness, hand weakness, finger weakness, leg weakness, neck weakness.

[0099] In some embodiments, the treatment of myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, includes improvement of clinical markers of MG progression. These markers include MG activity of daily living profile (MG-ADL) and quantitative Myasthenia Gravis (QMG) score for disease severity. In certain embodiments, MG-ADL is the primary objective for measuring improvement in MG.

[0100] The MG-ADL is an 8-point questionnaire that focuses on related symptoms and functional performance of activities of daily living (ADL) in pediatric subjects with MG. The 8 items of the MG-ADL are derived from the symptom-based components of the original 13-item QMG to assess impairments secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) disorders related to the effects from MG. On this functional status scale, each response is graded from 0 (normal) to 3 (most severe). The range of the total MG-ADL score is 0 to 24. A clinically meaningful improvement in a patient's MG-ADL would be a reduction of 2 or more points in the 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.

[0101] In some embodiments, pediatric patients being treated by the methods provided herein experience a change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score over time or 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 from baseline in MG-ADL score is 2 or more points on the MG-ADL scale.

[0102] The current QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item), each graded 0-3, with 3 being the most severe. The range of total QMG scores is 0-39. The QMG scoring system is considered to be an objective evaluation of the treatment of MG and is based on quantitative testing of the sentinel muscles. Higher scores indicated more weakness. QMG is preferably administered by a trained and qualified medical professional (e.g., physician, physician assistant, clinical nurse, nurse practitioner). QMG is preferably administered by the same medical professional for a given pediatric subject throughout the entire study, if possible, and at approximately the same time of day throughout the study.

[0103] In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline in QMG score after 22, 23, and 24 weeks of treatment. In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline in QMG score over time after administration of the last dose. In some embodiments, the change from baseline is a reduction of at least 2, 3, 4, 5, 6, 7, or 8 points in the patient's QMG 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 over time after administration of the last dose. In some embodiments, the change from baseline is at least a 2 point reduction in the patient's QMG 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 over time after administration of the last dose. In some embodiments, the change from baseline is at least a 3 point reduction in the patient's QMG 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 over time after administration of the last dose. In some embodiments, the change from baseline is at least a 4 point reduction in the patient's QMG 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 over time after administration of the last dose. In some embodiments, the change from baseline is at least a 5 point reduction in the patient's QMG 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 over time after administration of the last dose. In some embodiments, the change from baseline is at least a 6 point reduction in the patient's QMG 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 over time after administration of the last dose.In some embodiments, the change from baseline is at least a 7 point reduction in the patient's QMG 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 over time after administration of the last dose. In some embodiments, the change from baseline is an 8 point or greater reduction in the patient's QMG 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 over time after administration of the last dose.

[0104] The 15-item Myasthenia Gravis Qualify of Life (MG-QoL15) is a health-related quality of life assessment instrument specific for subjects with MG. The MG-QoL15 provides information about the subject's perception of impairment and disability, and the degree to which disease manifestations are tolerated, and is preferably designed to be easy to administer and interpret. The MG-QoL15 is completed by the subject. Total scores range from 0 to 60, with higher scores indicating a greater degree of MG-related dysfunction and greater dissatisfaction with MG-related dysfunction. The MG-QoL15 is preferably used to assess the subject's limitations associated with living with MG. Each of the 15 items was rated by the subject on a 3-point scale based on a recall period "over the past few weeks," with a maximum score of 30. Higher scores indicated more limitations.

[0105] In some embodiments, pediatric patients being treated by the methods provided herein experience a change from baseline in MG-QoL15 scores 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, pediatric patients being treated by the methods provided herein experience a change from baseline in MG-QoL15 scores 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%, 5-20%, 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%.

[0106] The Myasthenia Gravis Foundation of America Clinical Classification (MGFA) can be used to assess MG severity in subjects. The system includes five classes of disease severity ranging from Class I (ocular muscle weakness only) to Class V (subject is intubated). Classes II-IV are each further divided into two subclasses based on which muscle groups are primarily affected. The MGFA is preferably administered by a trained and qualified medical professional (e.g., physician, physician assistant, clinical nurse, nurse practitioner) and, if possible, is preferably assessed by the same person for a given subject throughout the entire study.

[0107] In some embodiments, pediatric patients being treated by the methods provided herein experience a shift 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, patients being treated by the methods provided herein experience a shift in MGFA classification over time after administration of the last dose. In some embodiments, the shift is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1-20%, 5-20%, 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%.

[0108] In some embodiments, pediatric patients being treated by the methods provided herein experience changes in neurological quality of life (Neuro-QoL-Fatigue). Neuro-QoL-Fatigue is a reliable and valid short 19-item fatigue survey completed by the subject for all items. Higher scores indicate more severe fatigue and a greater impact of MG on activity. A clinically significant improvement in a patient's Neuro-QoL-Fatigue score is reflected by a decrease in score over time after treatment or after administration of the last dose.

[0109] In some embodiments, pediatric patients being treated by the methods provided herein experience a change from baseline in 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, patients being treated by the methods provided herein experience a change from baseline in the Neuro-Fatigue scale over time after administration of the last dose. In some embodiments, the change from baseline in Neuro-QoL-Fatigue indicates an improvement. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1-20%, 5-20%, 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%.

[0110] In some embodiments, pediatric patients being treated by the methods provided herein experience changes in the EuroQol Five Dimension Five Level Quality of Life Questionnaire (5Q-5D-5L). The EQ-5D-5L is a standardized measure of health status developed by the EuroQol group to provide a simple general measure of health for clinical and economic evaluation. The EQ-5D-5L, as a measure of health-related quality of life, defines health in terms of five dimensions: mobility, self-care, daily activities, pain / discomfort, and anxiety / depression. Each dimension has three ordinal levels of severity: "no problems" (1), "some problems" (2), and "severe problems" (3). The overall health status is defined as a five-digit number. The health status defined by the five-dimensional classification can be converted into a corresponding index score that quantifies the health status, where -0.594 represents "severe problems" and 1 represents "no problems."

[0111] In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline in the EQ-5D-5L scale. In some embodiments, the change from baseline in the EQ-5D-5L scale indicates improvement. In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline in the EQ-5D-5L 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 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%, 5-20%, 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%.

[0112] In some embodiments, pediatric patients being treated by the methods provided herein experience a change from baseline in the EQ-5D-5Y scale. The EQ-5D-Y is a standardized, child-friendly instrument for use as a measure of health status, designed primarily for self-completion by children and adolescents, or with a proxy version completed by the child's caregiver. The EQ-5D-Y descriptive system includes five dimensions: mobility; caring for oneself (washing and getting dressed); usual activities; pain or discomfort; and feeling worried or unhappy. Each of the five dimensions is divided into three levels of perceived problems (level 1 indicating no problems, level 2 indicating some problems, and level 3 indicating many problems) (EuroQol 2021; EuroQol 2019). Participants select an answer for each of the five dimensions considering the response that best matches their health "today". The descriptive system can be expressed as a health state. The time it takes to complete the questionnaire will be approximately one minute, depending on age, health status, and setting.

[0113] In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline in the EQ-5D-5Y scale. In some embodiments, the change from baseline in the EQ-5D-5Y scale indicates improvement. In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline in the EQ-5D-5Y 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 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%, 5-20%, 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%.

[0114] In some embodiments, pediatric patients being treated by the methods provided herein experience a change in the Patient Global Impression of Change scale (PGI-C), which is a patient-based assessment of response to treatment on a 7-point Likert scale.

[0115] In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline in the PGI-C scale. In some embodiments, the change from baseline in the PGI-C scale indicates improvement. In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline in 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 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%, 5-20%, 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%.

[0116] In some embodiments, pediatric patients being treated by the methods provided herein experience a change in the Patient Global Impression of Severity Scale (PGI-S). The Patient Global Impression of Severity Scale (PGI-S) is a global index that can be used to grade the severity of a particular condition (a single condition scale). It is a simple, straightforward, and easy-to-use scale that is intuitive to clinicians. The PGI-S is a single question that asks patients to rate how their urinary tract condition is currently on a scale of 1 (normal) to 4 (severe).

[0117] In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline in the PGI-S scale. In some embodiments, the change from baseline in the PGI-S scale indicates improvement. In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline in the PGI-S 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 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%, 5-20%, 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%.

[0118] In some embodiments, patients being treated by the methods provided herein experience a change in the Columbia-Suicide Severity Rating Scale (C-SSRS). The C-SSRS is used to assess a patient's degree of suicidal ideation on a scale ranging from "no suicidal ideation" to "active suicidal ideation with specific plans and intent." (Posner 2011)

[0119] In some embodiments, pediatric patients treated with the methods provided herein experience a change from baseline in the C-SSRS scale. In some embodiments, the change from baseline in the C-SSRS scale indicates improvement. In some embodiments, pediatric patients treated with the methods provided herein experience a change from baseline in the C-SSRS 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 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%, 5-20%, 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%.

[0120] In some embodiments, patients being treated by the methods provided herein experience changes in the Pediatric Quality of Life Inventory Scale (PedsQL). The PedsQL measurement model is a modular approach to measuring health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. The PedsQL measurement model seamlessly integrates both generic core scales and disease-specific modules into one measurement system. The 23-item PedsQL generic core scales were designed to measure the core dimensions of health described by the World Health Organization, and role (school) functioning. The PedsQL can be completed by children and adolescents, with versions available for children and adolescents ages 5-7, 8-12, and 13-18. Parent-rated versions are available for children ages 2-4, 5-7, 8-12, and 13-18. The PedsQL inventory takes approximately 5 minutes to complete and can be self-administered by parents, children, and adolescents ages 8-18 after being introduced by a trained administrator. For younger children and as an alternative in special circumstances, clinicians can administer the inventory, providing instructions and all items are read word for word to the child or adolescent. Items on the PedsQL Generic Core Scales are reverse scored and converted to a 0-100 scale. Higher scores indicate better health-related quality of life: 0 ("never") = 100, 1 ("rarely") = 75, 2 ("sometimes") = 50, 3 ("often") = 25, and 4 ("almost always") = 0. Versions used: Teens report the acute version for children aged 13-18 years; Parents report the acute version for children aged 8-12 years; Parents report the acute version for children aged 5-7 years; Parents report the acute version for toddlers aged 2-4 years.

[0121] In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline in the PedsQL scale. In some embodiments, the change from baseline in the PedsQL scale indicates improvement. In some embodiments, pediatric patients treated by the methods provided herein experience a change from baseline in the PedsQL 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 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%, 5-20%, 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%.

[0122] 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 every two weeks in a therapeutically effective amount of about 1 mg / kg to about 100 mg / kg, or about 5 mg / kg to about 60 mg / kg. In some embodiments, the myasthenia gravis is generalized myasthenia gravis. In some embodiments, the myasthenia gravis is transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof. In some embodiments, the myasthenia gravis is transient 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 with a suboptimal response to a stable therapy for gMG. In some embodiments, the stable therapy for gMG includes an acetylcholinesterase inhibitor, a glucocorticosteroid, and an immunosuppressant. In some embodiments, the immunosuppressant is selected from azathioprine, mycophenolate mofetil / mycophenolic acid, methotrexate, cyclosporine, tacrolimus, and cyclophosphamide. In some embodiments, the method includes administering a pharmaceutical composition comprising administering an anti-FcRn antibody to the pediatric subject. In some embodiments, the anti-FcRn antibody is nipocalimab, RVT-1401 (HL161), rozanolixizumab (UCB7665), ALXN1830, ABY-039, or efgartigimod. In some embodiments, the anti-FcRn antibody is nipocalimab.

[0123] 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 preferred embodiments, the anti-FcRn antibody is preferably nipocalimab. In some embodiments, the therapeutically effective amount is about 1 mg / kg to about 100 mg / kg, about 5 mg / kg to about 60 mg / kg, about 5 mg / kg to about 15 mg / kg, about 15 mg / kg to about 60 mg / kg, about 15 mg / kg to about 30 mg / kg, or about 30 mg / kg to about 60 mg / kg of an anti-FcRn antibody. In some embodiments, the therapeutically effective amount is about 1 mg / kg, about 5 mg / kg, about 10 mg / kg, about 15 mg / kg, about 20 mg / kg, about 25 mg / kg, about 30 mg / kg, about 35 mg / kg, about 40 mg / kg, about 45 mg / kg, about 50 mg / kg, about 55 mg / kg, or about 60 mg / kg. In some embodiments, the therapeutically effective amount is 30 mg / kg. In some embodiments, the therapeutically effective amount is 15 mg / kg.

[0124] In some embodiments, the pharmaceutical composition is administered weekly, every two weeks, or monthly to the subject. In some embodiments, the pharmaceutical composition is administered to the subject as an initial loading dose and a maintenance dose, comprising an initial loading dose containing an anti-FcRn antibody at a dose of about 1 mg / kg to about 100 mg / kg, about 5 mg / kg to about 60 mg / kg, about 5 mg / kg to about 15 mg / kg, about 15 mg / kg to about 60 mg / kg, about 15 mg / kg to about 30 mg / kg, or about 30 mg / kg to about 60 mg / kg, and a maintenance dose containing an anti-FcRn antibody at a dose of about 5 mg / kg to about 45 mg / kg, about 5 mg / kg to about 15 mg / kg, about 15 mg / kg to about 45 mg / kg, or about 30 mg / kg to about 45 mg / kg, to the subject. In some embodiments, the pharmaceutical composition is administered to the subject as a loading dose and a maintenance dose, comprising a loading dose comprising an anti-FcRn antibody at a dose of 30 mg / kg, and a maintenance dose comprising an anti-FcRn antibody at a dose of 15 mg / kg. In a preferred embodiment, the anti-FcRn antibody is preferably nipocalimab.

[0125] In some embodiments, administration of the pharmaceutical composition to a pediatric patient for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, results in the patient exhibiting 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.

[0126] In some embodiments, administration of the pharmaceutical composition to a pediatric patient for treating myasthenia gravis treats transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, or improves ocular myasthenia, ptosis, difficulty chewing, dysphagia, inability to speak, dysphonia, difficulty breathing, inability to keep mouth closed, appearance of sadness or drowsiness, difficulty holding head upright, double vision, inability to speak, difficulty swallowing, changes in facial expression, shortness of breath, arm weakness, hand weakness, finger weakness, leg weakness, neck weakness.

[0127] In some embodiments, administration of the pharmaceutical composition to a pediatric patient results in a reduction in one or more immunoglobulin isotypes or total IgG in the patient. In some embodiments, the isotypes are 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%, 5-20%, 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 reduced immunoglobulin isotype is IgG1, IgG2, IgG3, IgG4, IgA, IgM, or IgE, or any combination thereof.

[0128] In some embodiments, administration of the pharmaceutical composition to a pediatric patient shows a reduction in autoantibodies in the patient, hi some embodiments, the autoantibodies are selected from the group consisting of anti-acetylcholine receptor (AChR), anti-muscle specific kinase (MuSK), anti-low density lipoprotein receptor-related protein 4 (LRP4), anti-agrin, anti-titin, anti-Kv1.4, anti-ryanodine receptor, anti-collagen Q, and anti-cortactin. In some embodiments, the reduction is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1-20%, 5-20%, 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%.

[0129] In some embodiments, the pharmaceutical composition is also administered with an additional therapeutic agent in addition to nipocalimab. In some embodiments, the additional therapeutic agent is an acetylcholinesterase inhibitor, pyridostigmine, pyridostigmine bromide (Mestinon), neostigmine, prednisone, azathioprine (Imuran), mycophenylate mofetil (CellCept), tacrolimus (Prograf), methotrexate, cyclosporine (Sandimmune, 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) nipocalimab.

[0130] In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, results in the pediatric patient exhibiting a change from baseline in MG-ADL score. In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis results in a change from baseline in MG-ADL score of 2 or more points on the MG-ADL scale. In some embodiments, administration of a pharmaceutical composition to a pediatric patient results in an improvement in the patient as measured by ACR score over time or at 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 a first dose of the pharmaceutical composition to the pediatric patient.

[0131] In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, results in the patient exhibiting a change from baseline in QMG 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 over time after administration of the last dose. In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis, results in the patient exhibiting a change from baseline in QMG score over time after administration of the last dose. In some embodiments, the change from baseline is at least a 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 24 week reduction in the patient's QMG score after 2, 3, 4, 5, 6, 7, or 8 points or more after 2, 4, 5, 6, 7, or 8 points or more 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 over time after administration of the last dose of the pharmaceutical composition. In some embodiments, the change from baseline is at least a 2 point reduction in the patient's QMG 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 over time after administration of the last dose of the pharmaceutical composition. In some embodiments, the change from baseline is at least a 3 point reduction in the patient's QMG 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 over time after administration of the last dose of the pharmaceutical composition. In some embodiments, the change from baseline is at least a 4 point reduction in the patient's QMG 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 over time after administration of the last dose of the pharmaceutical composition.In some embodiments, the change from baseline is at least a 5 point reduction in the patient's QMG 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 over time after administration of the last dose of the pharmaceutical composition. In some embodiments, the change from baseline is at least a 6 point reduction in the patient's QMG 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 over time after administration of the last dose of the pharmaceutical composition. In some embodiments, the change from baseline is at least a 7 point reduction in the patient's QMG 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 over time after administration of the last dose of the pharmaceutical composition. In some embodiments, the change from baseline is an 8 point or greater reduction in the patient's QMG 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 over time after administration of the last dose of the pharmaceutical composition.

[0132] In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, results in the patient exhibiting a change from baseline in 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 over time after administration of the last dose. In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, results in the patient exhibiting a change from baseline in MG-QoL15 score 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%, 5-20%, 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%.

[0133] In some embodiments, administration of the pharmaceutical composition to a pediatric patient for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, results in the patient exhibiting a shift 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, or over time after administration of the last dose. In some embodiments, administration of the pharmaceutical composition to a pediatric patient for treating myasthenia gravis, results in the patient exhibiting a shift in MGFA classification over time after administration of the last dose of the pharmaceutical composition. In some embodiments, the shift is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1-20%, 5-20%, 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%.

[0134] In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, results in a change from baseline in 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 a pharmaceutical composition to a pediatric patient for treating myasthenia gravis results in a change from baseline in the Neuro-QoL-Fatigue scale over time after administration of the last dose. In some embodiments, the change from baseline in Neuro-QoL-Fatigue indicates an improvement. In some embodiments, the change is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1-20%, 5-20%, 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%.

[0135] In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis results in a change from baseline in the EQ-5D-5L scale in transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof. In some embodiments, the change from baseline in the EQ-5D-5L scale indicates an improvement. In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis results in a change from baseline in the EQ-5D-5L 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 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%, 5-20%, 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%.

[0136] In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis results in a change from baseline in the EQ-5D-5Y scale in transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof. In some embodiments, the change from baseline in the EQ-5D-5Y scale indicates an improvement. In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis results in a change from baseline in the EQ-5D-5Y 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 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%, 5-20%, 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%.

[0137] In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, results in a change from baseline in the PGI-C scale. In some embodiments, the change from baseline in the PGI-C scale indicates improvement. In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis results in a change from baseline in 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 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%, 5-20%, 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%.

[0138] In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, results in a change from baseline in the PGI-S scale. In some embodiments, the change from baseline in the PGI-S scale indicates an improvement. In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, results in a change from baseline in the PGI-S 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 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%, 5-20%, 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%.

[0139] In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, results in a change from baseline in the C-SSRS scale. In some embodiments, the change from baseline in the C-SSRS scale indicates an improvement. In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, results in a change from baseline in the C-SSRS 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 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%, 5-20%, 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%.

[0140] In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, results in a change from baseline in the PedsQL scale. In some embodiments, the change from baseline in the PedsQL scale indicates an improvement. In some embodiments, administration of a pharmaceutical composition to a pediatric patient for treating myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, results in a change from baseline in the PedsQL 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 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%, 5-20%, 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%.

[0141] In some embodiments, a subject being treated with an anti-FcRn antibody for myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, does not experience a clinically significant increase in total cholesterol, high-density lipoprotein (HDL), estimated low-density lipoprotein (LDL), and triglyceride levels after being treated with the antibody. In some embodiments, the anti-FcRn antibody is M281. In some embodiments, a subject being treated with an anti-FcRn antibody for myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, does not experience a clinically significant increase in total cholesterol levels after being treated with the antibody. In some embodiments, a subject being treated with an anti-FcRn antibody for myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, does not experience a clinically significant increase in high density lipoprotein (HDL) levels after being treated with the antibody. In some embodiments, a subject being treated with an anti-FcRn antibody for myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, does not experience a clinically significant increase in estimated low density lipoprotein (LDL) levels after being treated with the antibody. In some embodiments, a subject being treated with an anti-FcRn antibody for myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, does not experience a clinically significant increase in triglyceride levels after being treated with the antibody. In some embodiments, subjects being treated with an anti-FcRn antibody for myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, do not experience a clinically significant increase in total cholesterol levels after treatment with M281.In some embodiments, subjects being treated with an anti-FcRn antibody for myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, do not experience a significant increase in high density lipoprotein (HDL) levels after being treated with M281. In some embodiments, subjects being treated with an anti-FcRn antibody for myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, do not experience a clinically significant increase in estimated low density lipoprotein (LDL) levels after being treated with M281. In some embodiments, subjects being treated with an anti-FcRn antibody for myasthenia gravis, transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome (CMS), or any combination thereof, do not experience a clinically significant increase in triglyceride levels after being treated with M281.

[0142] 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 a 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 level of calculated 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 a 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 level of estimated 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.

[0143] As used herein, the phrase "does not significantly increase" when used with respect to total cholesterol, high density lipoprotein (HDL), estimated low density lipoprotein (LDL), or triglyceride levels (measured) means that any increase is less than 30% compared to the levels before administration of an antibody or composition provided herein (baseline). As used herein, the phrase "does not experience a clinically significant increase" when used with respect to total cholesterol, high density lipoprotein (HDL), estimated low density lipoprotein (LDL), or triglyceride levels (measured) means that any increase is less than 30% compared to the levels before administration of an 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 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% or less.

[0144] As used herein, the term "change" with respect to baseline refers to the subject having an improvement compared to the subject's condition, score, symptom, etc. before being treated with an anti-FcRn antibody provided herein.

[0145] "Baseline" refers to a subject prior to treatment with a therapeutic agent, such as an anti-FcRn antibody, including those provided herein.

[0146] As provided herein, in some embodiments, improvement of symptoms or conditions is said to occur 24 weeks after the initiation of treatment. Although reference is made to determining whether such improvement is measurable 24 weeks after the initiation of treatment, in some embodiments, the improvement or change described herein occurs within 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 weeks. In some embodiments, the change or improvement continues for at least 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 weeks.

[0147] In some embodiments, the subject being treated for myasthenia gravis is a subject in need of treatment.

[0148] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise.

[0149] As used herein, the term "about" means that the numerical values ​​are approximate and that small variations do not significantly affect the practice of the disclosed embodiments. When numerical limitations are used, unless otherwise indicated by context, "about" means that the numerical values ​​can vary by ±10% and remain within the scope of the disclosed embodiments.

[0150] As used herein, "comprising" (and any form of comprising, such as "comprise," "comprises," and "comprised"), "having" (and any form of having, such as "have" and "has"), "including" (and any form of including, such as "includes" and "include"), or "containing" (and any form of containing, such as "contains" and "contain") are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. Any composition or method describing the term "comprising" should be understood to also describe such a composition consisting of, consisting of, or consisting essentially of the recited components or elements.

[0151] As used herein, the terms "individual," "subject," or "patient" may be used interchangeably and refer to any animal, including mammals such as mice, rats, other rodents, rabbits, dogs, cats, pigs, cows, sheep, horses, or primates, such as humans. As used herein, the term "mammal" refers to rodents (i.e., mice, rats, or guinea pigs), monkeys, cats, dogs, cows, horses, pigs, or humans. In some embodiments, the mammal is a human. In some embodiments, the subject is a pediatric subject.

[0152] As used herein, the phrase "in need of treatment" means that a subject has been identified as having a need for a particular method or treatment. In some embodiments, the identification can be by any diagnostic means. In any of the methods and treatments described herein, the subject may be in need of treatment. In some embodiments, the subject is in or moves to an environment where a particular disease, disorder, or condition is prevalent.

[0153] As used herein, the phrase "integers from X to Y" means any integer, including the endpoints. For example, the phrase "integers from 1 to 5" means 1, 2, 3, 4, or 5.

[0154] 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.

[0155] Other embodiments While the present disclosure has been described in relation to particular embodiments thereof, it will be understood that further modifications are possible, and the present application is generally intended to cover any variations, uses, or adaptations thereof, including such departures from the present disclosure in accordance with principles, within known or customary practice in the art to which the present disclosure pertains and which may be applied to the essential features previously described herein.

[0156] In some embodiments, the embodiments provided herein also include, but are not limited to, the following: 1. A method of treating pediatric myasthenia gravis in a pediatric patient in need thereof, comprising administering an initial loading dose of about 30 mg / kg to about 60 mg / kg of an anti-FcRn antibody, followed by a maintenance dose of about 15 mg / kg to about 30 mg / kg of an anti-FcRn antibody, wherein the anti-FcRn antibody is a heavy chain comprising an HCDR1 of SEQ ID NO:6, an HCDR2 of SEQ ID NO:7, and an HCDR3 of SEQ ID NO:8; a light chain comprising an LCDR1 of SEQ ID NO:3, an LCDR2 of SEQ ID NO:4, and an LCDR3 of SEQ ID NO:5; administering reduces serum IgG in 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; The method, wherein the pediatric myasthenia gravis is selected from transient 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 transient neonatal myasthenia gravis. 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 heavy chain variable region comprising an amino acid sequence having at least 95% identity to the sequence of SEQ ID NO: 10, and the light chain comprises a light chain variable region 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 heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 10, and the light chain comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 9. 9. The method of any one of embodiments 1-8, wherein administration is intravenous or subcutaneous. 10. The method according to any one of embodiments 1 to 9, wherein the administration comprises administering a pharmaceutical composition comprising about 10 mg / ml to about 60 mg / ml of an anti-FcRn antibody, about 20 mM to about 30 mM sodium phosphate, about 20 mM to about 30 mM sodium chloride, about 80 mg / ml to about 100 mg / ml of trehalose, and about 0.1% w / v to about 0.005% w / v of polysorbate 80. 11. The method of any one of embodiments 1-10, wherein the initial loading dose is about 60 mg / kg or about 30 mg / kg. 12. The method of any one of embodiments 1-11, wherein the maintenance dose is about 15 mg / kg or about 30 mg / kg. 13. Maintenance dose is: 1 week, 2 weeks, 3 weeks, 4 weeks, or 1 month after administration of the loading dose, and The method of any one of embodiments 1-12, wherein the maintenance dose is administered 1 week, 2 weeks, 3 weeks, 4 weeks, or 1 month after administration of the preceding maintenance dose. 14. The loading dose is infused into the pediatric patient within about 30 to about 90 minutes. The method of any one of embodiments 1-13, wherein the maintenance dose is infused into the pediatric patient within about 15 to about 60 minutes. 15. The method of any one of embodiments 1-14, wherein the serum IgG is IgG1, IgG2, IgG3, or IgG4, or any combination thereof, and the reduction is at least 20% of baseline, or at least 30% of baseline. 16. The method of any one of embodiments 1-15, wherein administration of the anti-FcRn antibody reduces serum albumin by up to 18%, up to 16%, up to 14%, up to 12%, up to 10%, up to 8%, up to 6%, up to 4%, or up to 2% of baseline serum albumin. 17. The administration reduces serum autoantibodies, 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 (LRP4), anti-agrin, anti-titin, anti-Kv1.4, anti-ryanodine receptor, anti-collagen Q, and anti-cortactin; The method of any one of embodiments 1-16, wherein 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 administration of the anti-FcRn antibody reduces anti-AChR antibodies by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 50%, or at least 25% of baseline anti-AChR antibodies. 19. The method of any one of embodiments 17 or 18, wherein administration of the anti-FcRn antibody reduces 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 baseline anti-MuSK antibody. 20. The method of any one of embodiments 1-19, wherein the patient achieves a change from baseline 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. 21. The method of any one of embodiments 1 to 20, wherein administration of the anti-FcRn antibody to a pediatric patient does not significantly increase the levels of total cholesterol, HDL, estimated LDL, and triglycerides in the subject compared to the levels before 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, An anti-FcRn antibody is administered intravenously or subcutaneously to a pediatric patient at an initial loading dose of about 30 mg / kg to about 60 mg / kg, followed by a maintenance dose of about 15 mg / kg to about 30 mg / kg of the anti-FcRn antibody; Anti-FcRn antibody, a heavy chain comprising an HCDR1 of SEQ ID NO:6, an HCDR2 of SEQ ID NO:7, and an HCDR3 of SEQ ID NO:8; a light chain comprising an LCDR1 of SEQ ID NO:3, an LCDR2 of SEQ ID NO:4, and an LCDR3 of SEQ ID NO:5; The pharmaceutical composition, wherein the pediatric myasthenia gravis is selected from transient neonatal myasthenia gravis, juvenile myasthenia gravis, congenital myasthenia gravis syndrome, or any combination thereof. 23. The pharmaceutical composition according to embodiment 22, wherein the loading dose is about 60 mg / kg or about 30 mg / kg and the maintenance dose is about 15 mg / kg or about 30 mg / kg. 24. The pharmaceutical composition of embodiment 22, wherein the pediatric myasthenia gravis is transient neonatal myasthenia gravis. 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 childhood myasthenia gravis is congenital myasthenia gravis syndrome.

[0157] 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

[0158] Example 1. Study Design. A Phase 2 / 3, open-label, multicenter study to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, tolerability, efficacy, and activity of intravenous nipocalimab in pediatric subjects (ages 2 to <18 years) with gMG who have an inadequate clinical response to ongoing stable standard of care.

[0159] A screening period of up to 28 days will allow sufficient time to conduct screening assessments and determine study eligibility.

[0160] A total of 12 subjects were proposed, six in each of two age cohorts: Cohort 1) ≥12 to <18 years, and Cohort 2) ≥2 to <12 years.

[0161] The active treatment phase will include cohorts 1 and 2, which will be unblinded and open to all male and female pediatric subjects who meet the study-specific inclusion and exclusion criteria. The study population will consist of boys and girls who have received a diagnosis of gMG with generalized muscle weakness, have an inadequate clinical response to ongoing stable standard of care, and meet clinical criteria for gMG as defined by the Myasthenia Gravis Foundation of America (MGFA) clinical classification class II a / b, III a / b, or IV a / b at screening. Additionally, participants will have a positive serological test for gMG-associated pathogenic autoantibodies (anti-AChR and / or anti-MuSK).

[0162] Pediatric patients will be excluded from the study for: 1) having a history of any other medical disorder, including severe and / or uncontrolled hepatic, gastrointestinal, renal, pulmonary, cardiovascular, psychiatric, neurological or musculoskeletal disorders, or laboratory abnormalities, that, in the opinion of the investigator, may prevent the participant from fully participating in the study or may compromise the participant's safety or the validity of the study results. 2) having any confirmed or suspected clinical immunodeficiency syndrome unrelated to his / her gMG treatment, or having a family history of congenital or inherited immunodeficiency, unless confirmed to be absent in the participant. 3) having the presence of MGFA class I disease or MG crisis (MGFA class V) at screening, a history of MG crisis within 1 month of screening, or qualitative muscle weakness (and / or "burnout" MG). 4) being gastric tube dependent or ventilator dependent for nutritional needs. 5) actively undergoing radiation or chemotherapy treatment for unresected thymoma / malignant thymoma. Participants with stable benign thymoma (e.g., stage I or IIa) that has not been treated for the past 3 years may be allowed after discussion with the sponsor's medical monitor. 6) Has undergone thymic ablation within 12 months prior to screening or if thymic ablation is planned during the active treatment phase of the study. 7) Has current or history of any neurological disorder other than MG that may interfere with the accuracy of study assessments (including, but not limited to, any chronic neurodegenerative disease, altered level of consciousness, dementia, abnormal mental status, major congenital neurological disorder, Lambert-Eaton myasthenic syndrome, drug-induced MG, or hereditary myasthenic syndrome). 8) Currently have a malignancy or have a history of malignancy within 3 years prior to screening (excluding localized basal cell and / or squamous cell skin cancer that has been adequately treated and has no evidence of recurrence for at least 3 months [defined as a minimum of 12 weeks] prior to the first study intervention, or in situ cervical intraepithelial neoplasia that has been treated and has no evidence of recurrence for at least 3 months prior to the first study intervention). 9) Known allergy, hypersensitivity, or intolerance to nipocalimab or its excipients (see IB).10) Demonstrated previous severe immediate hypersensitivity reaction such as anaphylaxis to a therapeutic protein (e.g., monoclonal antibody). 11) Experienced myocardial infarction, unstable ischemic heart disease, or stroke within 12 weeks of screening. 12) Prior / concomitant treatment: Currently taking an IgG Fc-related protein therapeutic, or an Fc-conjugated therapeutic that includes factor or enzyme replacement. Received rituximab within 6 months prior to the first dose of the study intervention. Received a live vaccine within 3 months prior to screening or is known to require receiving a live vaccine during the study or at least 3 months after the last dose of the study intervention. Received plasmapheresis, immunoadsorption therapy, or IVIg within 4 weeks prior to baseline. Has 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 corticosteroids, intra-articular corticosteroids, topical corticosteroids, or ocular corticosteroids are not excluded. Have another medical condition requiring immunosuppressants unless the drug has been on the drug for at least 6 months, the dose has been stable for at least 3 months prior to baseline, and the drug and dose are expected to remain stable during the study. Have previously received nipocalimab. 13) Infection or predisposition to infection: have had a severe infection within 8 weeks prior to screening, including opportunistic infections requiring parenteral anti-infectives and / or hospitalization (e.g., pneumonia, biliary tract infection, diverticulitis, Clostridium difficile infection, cytomegalovirus, pneumocystis, aspergillosis, etc.) and / or are assessed by the investigator as severe / clinically significant. Participants may be re-screened after the 8-week exclusion period has passed. have a chronic infection (e.g., bronchiectasis, chronic osteomyelitis, chronic pyelonephritis) or require chronic treatment with anti-infectives (e.g., antibiotics, antivirals). If you test positive for hepatitis B virus (HBV) infection.Are seropositive for antibodies to Hepatitis C virus (HCV) unless they meet one of the following conditions: have a history of successful treatment defined as being negative for HCV RNA at least 24 weeks after completing antiviral treatment and have a negative HCV RNA test result at screening, or are seropositive but have a negative HCV RNA test result at least 24 weeks prior to screening and have a negative HCV RNA test result at screening. Have a history of positive human immunodeficiency virus (HIV) 1 or HIV 2 antibodies, or have a positive HIV test at screening.

[0163] The study consists of a screening period of up to 4 weeks, a 24-week active treatment phase, and a long-term extension (LTE) phase.

[0164] Cohort 1 will enroll adolescents (ages 12-18) to evaluate PK, PD, safety, and activity of the investigational drug treatment. Twelve weeks after all participants are enrolled in cohort 1, an interim analysis will evaluate PK, PD, and safety data and, if acceptable, begin the study in cohort 2 (participants ages 2-12). Once adolescents are enrolled, younger subjects ages 2-12 may be enrolled. All subjects will receive the investigational drug via IV infusion over 15-30 minutes every 2 weeks. Participants in cohort 1 of the study will receive a single 30 mg / kg loading dose followed by 15 mg / kg every 2 weeks [q2w]. Dosing for cohort 2 will be modeled based on all extant PK and PD data available at the time of the interim analysis, including adult data from Phase 1-3 studies and adolescent data from cohort 1 of this study. A total of at least 12 subjects will be studied, with at least 6 in each of the two age cohorts (adolescents and younger children).

[0165] The study duration is 24 weeks with the option to participate in a long term extension (LTE) after study completion; subjects who discontinue early or do not participate in the LTE after completing the study will undergo a safety assessment 8 weeks after ending enrollment. The LTE is expected to be approximately 104 weeks (approximately 2 years) in duration. All Cohort 1 participants in the LTE phase of the study will have the option to receive nipocalimab infusions q2w (15 mg / kg) or q4w (30 mg / kg) or change background concomitant medications based on the investigator's discretion. Options for changing dose and regimen for Cohort 2 participants during the LTE phase will be modeled and based on all extant PK and PD data available at the time of the interim analysis, including adult data from Phase 1-3 studies and adolescent data from Cohort 1 of this study. Other dosing regimens should not be used. Participants who discontinue early or do not participate in the LTE after completing the study will undergo a safety follow-up visit 8 weeks after the last infusion of the study intervention.

[0166] Blood samples will be collected at selected visits in the study to assess the PK and PD of the investigational drug in pediatric participants with gMG. Serum samples for immunogenicity assessment will be collected at selected visits in the study. Biomarker samples will be collected to assess the mechanism of action of the investigational drug or may help identify population subgroups that respond differently to an intervention.

[0167] The duration of the active treatment phase (24 weeks) is expected to be sufficient to evaluate nipocalimab's mechanism of action and activity and safety based on the results of the adult Phase 2 study, which demonstrated efficacy on MG-ADLs as early as Week 2 and sustained through Day 57 (the primary evaluation time point in the adult Phase 2 study). Maintenance of efficacy of nipocalimab, as well as the long-term safety of nipocalimab, will be further evaluated in the LTE phase.

[0168] Primary study parameters / study outcomes:Effect of nipocalimab on total serum IgG in pediatric participants 2 to <18 years of age with gMG with an inadequate clinical response to ongoing stable standard of care.Safety and tolerability of treatment with nipocalimab in pediatric participants 2 to <18 years of age with gMG with an inadequate clinical response to ongoing stable standard of care.Pharmacokinetics of nipocalimab in pediatric participants 2 to <18 years of age with gMG with an inadequate clinical response to ongoing stable standard of care.All primary PK and IgG endpoints will be summarized descriptively for the evaluable population and for each age cohort (2 to <12 years, or 12 to <18 years) over time.

[0169] Secondary endpoints include: Activity of nipocalimab in gMG as measured by change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) efficacy score. Activity of nipocalimab in gMG as measured by change from baseline in Quantitative Myasthenia Gravis (QMG) efficacy score. Effect on quality of life as measured by the European Quality of Life 5 Dimension Young (EQ-5D-Y) tool. Effect on fatigue as measured by the Neurological Quality of Life (Neuro-QoL) Pediatric Fatigue score. All secondary endpoints will be summarized descriptively for the evaluable population and for each age cohort (2 to <12 years, or 12 to <18 years) over time.

[0170] Exploratory endpoints include: Relationships between nipocalimab dose, PK of nipocalimab, total serum IgG, MG-ADL score and QMG score assessed by a PK-PD model. Effect of nipocalimab treatment on autoantibody levels (anti-AChR and anti-MuSK). Effect on health-related quality of life as measured by the Pediatric Quality of Life Inventory (PedsQL). All exploratory endpoints will be summarized descriptively over time for each age cohort (2 to <12 years or 12 to <18 years).

[0171] Safety assessments will include collection of AEs and SAEs, use of concomitant medications, laboratory tests (including chemistry, hematology, lipid profile, urinalysis, and tests for total serum IgG and diphtheria / tetanus vaccine titers), ECG, vital signs, physical examination, and Tanner staging. A urine pregnancy test will be performed only for girls of childbearing potential. In addition, the occurrence of suicidal ideation will be assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS). Severe or serious infections, hypoalbuminemic events (<20 g / L), and opportunistic infections will be considered adverse events of particular interest (AESIs).

[0172] Example 2. Nipocalimab is safe and well tolerated in patients with gMG. Pediatric subjects are evaluated using one or more of the following before treatment with nipocalimab: physical examination, C-SSRS, vital signs, 12-lead ECG, and urinalysis. In addition, blood and serum are collected for exploratory biomarker analysis, Ig type analysis, and clinical laboratory evaluation. Subjects with myasthenia gravis who have an inadequate clinical response to ongoing stable standard treatment or subjects with gMG are evaluated using physical examination, C-SSRS, vital signs, 12-lead ECG, urinalysis, blood and serum evaluation tests before treatment with nipocalimab to generate a baseline score. Subjects are administered nipocalimab at a single dose or at a loading dose and maintenance dose every 2 weeks for 24 weeks. After 24 weeks and throughout the study, subjects are evaluated for changes in vital signs, clinical laboratory values, and C-SSRS scores.

[0173] Example 3. Modeling of intravenous dosing. Various dosing regimens of M281 are modeled based on clinical data from adolescent patients. The impact of various dosing regimens on myasthenia gravis activities of daily living (MG-ADL) is modeled. Modeled doses include about 5 mg / kg, about 10 mg / kg, about 15 mg / kg, about 20 mg / kg, about 25 mg / kg, about 30 mg / kg, about 40 mg / kg, about 45 mg / kg, about 50 mg / kg, about 55 mg / kg, and about 60 mg / kg. Based on this modeling, dosing regimens for younger patients are derived.

[0174] Example 4. Treatment of myasthenia gravis with anti-FcRn antibodies results in a change from baseline in the MG-ADL scale. Pediatric subjects are assessed using the Myasthenia Gravis-Activities of Daily Living (MG-ADL) scale prior to treatment with nipocalimab. Subjects with myasthenia gravis or subjects with gMG who have an inadequate clinical response to ongoing stable standard treatment are assessed using the MG-ADL prior to treatment with nipocalimab to generate an MG-ADL score. Subjects are administered nipocalimab at a single dose or a loading dose and a maintenance dose every 2 weeks for 24 weeks. After 24 weeks and throughout the study, subjects are assessed for change in MG-ADL score at day 1, week 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 are assessed using the MG-ADL scale and are found to achieve a change from baseline in the MG-ADL scale.

[0175] Example 5. Treatment of myasthenia gravis with anti-FcRn antibodies results in changes from baseline in the QMG and MG-QoL15r scales. Subjects are assessed using the QMG and MG-QoL15r scales prior to treatment with nipocalimab. Subjects with myasthenia gravis or subjects with gMG who have an inadequate clinical response to ongoing stable standard treatment are assessed using the QMG and MG-QoL15r scale prior to treatment with nipocalimab to generate QMG and MG-QoL15r scores. Subjects are administered nipocalimab at a single dose or loading and maintenance doses every 2 weeks for 24 weeks. After 24 weeks and throughout the study, subjects are assessed for changes in QMG and MG-QoL15r scores at days 1, 2, 4, 8, 12, 16, 20, 22, and 24. After 24 weeks, and throughout the study, subjects are assessed using the QMG and MG-QoL15r scales and are found to achieve changes from baseline in the QMG and MG-QoL15r scales.

[0176] Example 6. Treatment of myasthenia gravis with anti-FcRn antibodies results in changes from baseline in Neuro-QoL-pediatric fatigue, EQ-5D-5Y, MGFA, PGI-C, PGI-S, and PedsQL scales. Pediatric subjects are assessed prior to treatment with nipocalimab using the Neuro-QoL-pediatric fatigue (older cohort only), EQ-5D-5Y (older cohort only), MGFA, PGI-C (older cohort only), PGI-S (older cohort only), and PedsQL scales. Subjects with myasthenia gravis or subjects with gMG who have an inadequate clinical response to ongoing stable standard of care are assessed prior to treatment with nipocalimab using the Neuro-QoL-Fatigue (older cohorts only), EQ-5D-5Y (older cohorts only), MGFA, PGI-C (older cohorts only), PGI-S (older cohorts only), and PedsQL scales to generate Neuro-QoL-Pediatric Fatigue (older cohorts only), EQ-5D-5Y (older cohorts only), MGFA, PGI-C (older cohorts only), PGI-S (older cohorts only), and PedsQL scores. Pediatric subjects are administered nipocalimab as a single dose or as a loading and maintenance dose every 2 weeks for 24 weeks. After 24 weeks and throughout the study, pediatric subjects are evaluated for change in Neuro-QoL-Fatigue, EQ-5D-5Y, PGI-C, PGI-S, and PedsQL scores at Day 1 (excluding PGI-C), Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 22, and Week 24. After 24 weeks and throughout the study, pediatric subjects are evaluated for change in MGFA scores at Day 1 and Week 12. After 24 weeks and throughout the study, pediatric subjects are evaluated using the Neuro-QoL-Pediatric Fatigue, EQ-5D-5Y, MGFA, PGI-C, PGI-S, and PedsQL scales and found to achieve change from baseline in the Neuro-QoL-Pediatric Fatigue, EQ-5D-5Y, MGFA, PGI-C, PGI-S, and PedsQL scales.

[0177] Example 7. Treatment of pediatric myasthenia gravis with nipocalimab does not elevate cholesterol to clinically significant levels. Elevations in total cholesterol and low-density lipoprotein (LDL) have been recently reported with another experimental anti-FcRN antibody, not nipocalimab, in the same pharmacological class of FcRn antagonists. This finding prompted a review of lipid data in sponsor-completed, ongoing nipocalimab studies. In phase 1 healthy volunteer and phase 2 generalized myasthenia gravis studies, asymptomatic dose-dependent reversible elevations in non-fasting mean total cholesterol were observed to 25% of baseline. At the highest dose of 60 mg / kg every 2 weeks (Q2W), the mean percent change in total cholesterol increased to a stable maximum of 21%-23% above baseline within 1 month of starting dosing and decreased to near baseline levels 1-2 months after the last dose. As a result of these findings, the following will be evaluated: 1) assessment of lipids (total cholesterol, HDL, estimated LDL, and triglycerides) in fasting and non-fasting states at multiple time points during and off treatment; 2) exclusion criteria for patients with recent significant cardiovascular events; and 3) recommendations for lipid dyslipidemia management according to local health guidelines.

[0178] Example 8. Pediatric Dose Justification. The dose level and dosing regimen proposed for cohort 1 of this Phase 2 / 3 study in adolescent participants with gMG (i.e., 30 mg / kg IV loading dose on day 1 followed by 15 mg / kg IV q2w maintenance dose starting week 2) was based on the dose level and dosing regimen selected for the Phase 3 study in adult participants with gMG. The dose level and dosing regimen for the adult Phase 3 gMG study was based on extensive modeling and simulation of dose-response relationships for IgG and MG-ADL using observed data from the adult Phase 2 study in participants with gMG, as well as data from adult Phase 1 and Phase 2 studies. Dosing for Cohort 2 of the study will be modeled based on all extant PK and PD data available at the time of the interim analysis, including adult data from Phase 1-3 studies and adolescent data from Cohort 1 of the study, as proposed in Example 1. In the adult phase 2 gMG study, rapid dose-dependent IgG decline was observed 1 week after the first dose in all dose groups, with maximum IgG decline achieved at week 2 in the 60 mg / kg single dose group and the 60 mg / kg q2w group. Dose-dependent improvements in MG-ADL scores were also observed, suggesting a correlation between IgG decline and improvement in MG-ADL scores. Importantly, nipocalimab was generally well tolerated across all dose groups. Population PK / PD / efficacy modeling analyses were performed using data obtained from nipocalimab adult phase 1 and 2 studies to evaluate the relationship between PK, IgG decline, and MG-ADL, in addition to other efficacy and safety endpoints (including serum albumin and cholesterol). Results showed that the q2w dosing interval provided more sustained IgG decline and MG-ADL reduction at all simulated dose levels when compared with the q4w dosing interval.Although modeling and simulation suggested numerical differences in IgG reduction and MG-ADL reduction between the 15mg / kg q2w and 30mg / kg q2w dosing regimens (model-predicted mean IgG reduction of 73.8% vs. 79.4%, respectively), the additional 5.6% IgG reduction at 30mg / kg q2w leads to minimal additional MG-ADL improvement at steady-state trough beyond the improvement expected at 15mg / kg q2w (Figure 1). Thus, the 15mg / kg q2w dosing regimen is selected as the single maintenance dose regimen to be studied for the adult Phase 3 gMG study since this is a rare disease with high unmet need. Lower doses will likely result in suboptimal efficacy, while higher doses may not result in as large a difference in efficacy as predicted for gMG. The predicted exposures at a 30 mg / kg IV loading dose on day 1 followed by a 15 mg / kg IV q2w maintenance dose are well below the PK exposures observed from the 60 mg / kg q2w dosing regimen in the adult Phase 2 gMG study, which was generally well tolerated based on currently available safety data. The dosing regimen planned for the adult Phase 3 gMG study is expected to have a mean <20% albumin reduction and <20% total cholesterol increase at steady state. The magnitude of albumin reduction and total cholesterol increase is not expected to be clinically significant and is less than that observed in previous adult studies with 30 mg / kg IV weekly or 60 mg / kg IV q2w dosing regimens. Thus, the doses proposed for the adult Phase 3 gMG study are expected to be safe and well tolerated. To propose a dosing regimen for adolescent participants with gMG, a population PK / receptor occupancy (RO) / IgG model was developed using data from adults and this model was adapted to dose selection in pediatric participants with gMG.Based on data from the literature, the fitted model accounted for 1) lower clearance (CL) and volume of distribution (V) in pediatric patients (CL and V were scaled by body weight according to allometry), and 2) age- and / or body weight-dependent FcRn and IgG at baseline in pediatric patients (FcRn and IgG were scaled by age and / or body weight) (Hardiansyah 2018). Results from the model-based simulation demonstrated comparable PK and IgG profiles between adolescent and adult patients with gMG when treated with the proposed dose and dosing regimen (Figure 2). Therefore, the dose and dosing regimen selected for the adult Phase 3 gMG study will also be used for cohort 1 of this study in adolescent patients aged 12-18 years, and no dose adjustments will be required. After adolescent participants in cohort 1 complete the first 12 weeks of treatment with nipocalimab, an interim analysis will be conducted to evaluate PK, PD, and safety data. The dose regimen for children (ages 2 to <12 years) in Cohort 2 will be selected based on PK-PD modeling and simulations using all existing PK and PD data available at the time of the interim analysis, including adult data from Phase 1-3 studies and adolescent data from Cohort 1 of this study. In the interim PK-PD modeling and simulations, CL and V are scaled by weight or body surface area (BSA), and FcRn and IgG are scaled by age, weight, or BSA. Dose adjustments may be required for children in Cohort 2 depending on the results from the interim analysis.

[0179] The embodiments and examples provided herein demonstrate that anti-FcRn antibodies, such as, but not limited to, nipocalimab, are effective in treating myasthenia gravis, as measured by one or more of the indicators and outcomes provided herein.

[0180] The disclosures of each and every patent, patent application, and publication cited herein are incorporated herein by reference in their entirety. Although various embodiments have been disclosed with reference to certain aspects, it is apparent that other aspects and modifications of these embodiments may be devised by those skilled in the art without departing from the true spirit and scope of the embodiments. It is intended that the appended claims be construed to include all such aspects and equivalent modifications.

Claims

1. 1. A pharmaceutical composition for treating pediatric myasthenia gravis in a pediatric patient in need thereof, comprising an anti-FcRn antibody, administered an initial loading dose of about 30 mg / kg to about 60 mg / kg of an anti-FcRn antibody, followed by a maintenance dose of about 15 mg / kg to about 30 mg / kg of said anti-FcRn antibody; The anti-FcRn antibody a heavy chain comprising an HCDR1 of SEQ ID NO:6, an HCDR2 of SEQ ID NO:7, and an HCDR3 of SEQ ID NO:8; and a light chain comprising an LCDR1 of SEQ ID NO:3, an LCDR2 of SEQ ID NO:4, and an LCDR3 of SEQ ID NO:

5. Pharmaceutical compositions.

2. 2. The pharmaceutical composition of claim 1, wherein the childhood myasthenia gravis is transient neonatal myasthenia.

3. The pharmaceutical composition according to claim 1, wherein the pediatric myasthenia gravis is juvenile myasthenia gravis.

4. The pharmaceutical composition according to claim 1, wherein the childhood myasthenia gravis is congenital myasthenia gravis syndrome.

5. 2. The pharmaceutical composition 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. 2. The pharmaceutical composition of claim 1, wherein the heavy chain comprises a heavy chain variable region comprising an amino acid sequence having at least 95% identity to the sequence of SEQ ID NO: 10, and the light chain comprises a light chain variable region comprising an amino acid sequence having at least 95% identity to the sequence of SEQ ID NO:

9.

7. 2. The pharmaceutical composition 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. 2. The pharmaceutical composition of claim 1, wherein the heavy chain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 10 and the light chain comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO:

9.

9. The pharmaceutical composition of claim 1 , wherein the administration is intravenous or subcutaneous.

10. 2. The pharmaceutical composition of claim 1, wherein the initial loading dose is about 60 mg / kg or about 30 mg / kg.

11. 2. The pharmaceutical composition of claim 1, wherein the maintenance dose is about 15 mg / kg or about 30 mg / kg.

12. The maintenance dose is administered weekly, biweekly, triweekly, quadruple, or monthly following administration of the loading dose; and 10. The pharmaceutical composition of claim 1, which is administered weekly, biweekly, triweekly, 4weekly, or monthly following administration of a preceding maintenance dose.

13. said loading dose is infused into said pediatric patient within about 30 minutes to about 90 minutes; 10. The pharmaceutical composition of claim 1, wherein the maintenance dose is infused into the pediatric patient within about 15 to about 60 minutes.

14. 2. The pharmaceutical composition of claim 1, wherein the serum IgG is IgG1, IgG2, IgG3, or IgG4, or any combination thereof, and the reduction is at least 20% from baseline, or at least 30% from baseline.

15. 2. The pharmaceutical composition of claim 1, wherein the administration of the anti-FcRn antibody reduces serum albumin by up to 18%, up to 16%, up to 14%, up to 12%, up to 10%, up to 8%, up to 6%, up to 4%, or up to 2% of baseline serum albumin.

16. said administering reducing serum autoantibodies; 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 (LRP4), anti-agrin, anti-titin, anti-Kv1.4, anti-ryanodine receptor, anti-collagen Q, and anti-cortactin; 2. The pharmaceutical composition of claim 1, wherein 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.

17. 17. The pharmaceutical composition of claim 16, wherein said administration of said anti-FcRn antibody reduces 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 baseline anti-AChR antibody.

18. 17. The pharmaceutical composition of claim 16, wherein said administration of said anti-FcRn antibody reduces 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 baseline anti-MuSK antibody.

19. 2. The pharmaceutical composition of claim 1, wherein the patient achieves a change from baseline 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.

20. 2. The pharmaceutical composition of claim 1, wherein said administration of said anti-FcRn antibody to said pediatric patient does not significantly increase total cholesterol, HDL, estimated LDL, and triglyceride levels in said patient compared to levels prior to said administration of said anti-FcRn antibody.

21. The pharmaceutical composition of claim 1, wherein the loading dose is 45 mg / kg and the maintenance dose is 25 mg / kg.

22. The pharmaceutical composition of claim 1, wherein the loading dose is 30 mg / kg and the maintenance dose is 15 mg / kg.

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