FCRN ANTIBODY COMPOSITIONS

Description

1 / 28 FCRN ANTIBODY COMPOSITIONS Separated from BR112021000755-5, filed on July 19, 2019. FIELD OF INVENTION

[001] This revelation pertains to Fc receptor antibody compositions (FcRn). BACKGROUND

[002] Numerous autoimmune and alloimmune diseases are mediated by pathogenic antibodies. The stability, activity, and transport of pathogenic antibodies depend on the neonatal Fc receptor (FcRN), a type I transmembrane protein that functions as an intracellular vesicular trafficking protein that binds to IgG and serum albumin. For example, many fetal and neonatal immune diseases result from the transfer of maternal antibodies from a pregnant woman, especially a pregnant woman with an immunological disease, to the fetus via the human neonatal Fc receptor (FcRN) in the placenta. SUMMARY

[003] This disclosure pertains to compositions comprising an anti-FcRn antibody (compositions M281). The compositions include a complete, intact antibody (i.e., an antibody having two antibody light chains and two antibody heavy chains) and size variants thereof that do not include two antibody heavy chains and two antibody light chains and instead include two antibody heavy chains and only a single antibody light chain. Thus, the pharmaceutical composition aM281 may include: an antibody (LHHL) comprising two heavy chains comprising or consisting of the amino acid sequence SEQ ID NO:2 and two light chains comprising or consisting of the amino acid sequence SEQ ID NO:1, wherein the composition comprises a major protein component having a molecular weight of 140,000 to 145,000 Da (e.g., Petition 870260064109, dated 06 / 29 / 2026, p. 13 / 104 2 / 28 140,500 to 143,000 Da) and a secondary protein component with a molecular weight of 118,000 to 120,000 Da (e.g., 119,000 to 120,000 Da or 119,150 to 119,350 Da), wherein the primary component has at least 80% (81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99%) by weight of the protein in the composition, and the secondary component has at least 0.8%, 1%, 2%, 3% by weight, but not more than 20% (19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5 or 4% of the protein in the composition. Thus, for example, the secondary protein component with a molecular weight of 118,000 to 120,000 Da may have 0.8 to 2%, 1 to 2%, 0.8 to 3% or 1 to 4% by weight of the protein in the composition.

[004] In various embodiments: the major protein component has at least 99% by weight of protein in its composition; the minor protein component comprises an antibody variant comprising two heavy chains and one light chain; the antibody variant comprises an unpaired heavy chain (comprising or consisting of the amino acid sequence of SEQ ID NO:2) and a paired heavy chain (comprising or consisting of the amino acid sequence of SEQ ID NO:2) and light chain (comprising or consisting of the amino acid sequence of SEQ ID NO:1); wherein the antibody variant comprises an unpaired heavy chain comprising a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO:2, wherein C, at position 219, is substituted for dehydroalanine;and the secondary protein component comprises: a) a first antibody variant comprising an unpaired heavy chain (comprising or consisting of the amino acid sequence of SEQ ID NO:2) and a paired heavy chain (comprising or consisting of the amino acid sequence of SEQ ID NO:2) and light chain (comprising or consisting of the sequence of; Petition 870260064109, dated 06 / 29 / 2026, p. 14 / 104 3 / 28 amino acids of SEQ ID NO:); and b) a second antibody variant comprising an unpaired heavy chain, comprising a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 2 in which C, at position 219, is replaced by dehydroalanine.

[005] A method for preparing a pharmaceutical composition is described in this document. Wherein the method comprises: providing to a composition an antibody comprising a heavy chain comprising the amino acid sequence SEQ ID NO:2 and a light chain comprising the amino acid sequence SEQ ID NO:1; determining whether the composition comprises a major protein component having a molecular weight of 140,000 to 145,000 Da (e.g., 140,500 to 143,000 Da) and a minor protein component having a molecular weight of 118,000 to 120,000 Da (e.g., 119,000 to 120,000 Da or 119,150 to 119,350 Da); Combining the composition with one or more pharmaceutically acceptable excipients to prepare the pharmaceutical composition is only permitted if the composition comprises a major protein component having a molecular weight of 140,000 to 145,000 Da (e.g., 140,500 to 143,000 Da) and a minor protein component with a molecular weight of 118,000 to 120,000 Da (e.g., 119,000 to 143,000 Da).000 to 120,000 Da or 119,150 to 119,350 Da).

[006] In several aspects of the method: the prepared pharmaceutical composition comprises 28 to 32 mg / ml of an antibody comprising a heavy chain comprising the amino acid sequence of SEQ ID NO:2 and a light chain comprising the amino acid sequence of SEQ ID NO:1; wherein the prepared pharmaceutical composition comprises 9 to 11 mg / ml of an antibody comprising a heavy chain comprising the amino acid sequence of SEQ ID NO:2 and a light chain comprising the sequence of Petition 870260064109, dated 06 / 29 / 2026, p. 15 / 104 4 / 28 amino acids of SEQ ID NO:1; the method further includes combining the composition with one or more pharmaceutically acceptable excipients to prepare only the pharmaceutical composition if the main component has at least 90% by weight of the protein in the composition and the secondary component has at least 3% by weight of the protein in the composition; wherein the determining step comprises electrophoresis or chromatography; and wherein the delivery step comprises culture cells expressing the heavy chain and the light chain.

[007] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by a person skilled in the art to which this invention pertains. The methods and materials described herein are for use in the present invention; other suitable methods and materials known in the art may also be used. The materials, methods, and examples are for illustrative purposes only and are not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, this descriptive report, including the definitions, shall prevail.

[008] Other features and advantages of the invention will become apparent from the following detailed description and figures, and claims. DESCRIPTION OF THE DRAWINGS

[009] Figure 1 shows a representative capillary electrophoresis electropherogram (CE-SDS) of the M281 composition measured under unreduced conditions; the predominant intact IgG identified as (2) and the size variant identified as (1).

[0010] Figure 2 shows representative data of the composition Petition 870260064109, dated 06 / 29 / 2026, page 16 / 104 5 / 28 M281 analyzed by hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC LC-MS); (A) UV chromatogram of composition M281 analyzed by hydrophilic interaction liquid chromatography with predominant light-heavy-heavy-light chain, identified as (2) and size variant identified as (1); (B) base peak chromatogram from mass spectrometry with predominant light-heavy-heavy-light chain identified as (2) and size variants identified as (la, retention time 12.42 min.; lb, retention time 12.68 min.).

[0011] Figures 3A to 3B show representative mass spectrometry results of selected fractions isolated by hydrophilic interaction liquid chromatography; (A) shows mass spectrometry results of the fraction comprising Figure 2 (1a); (B) shows mass spectrometry results of the fraction comprising Figure 2 (1b).

[0012] Figure 4 shows a cartoon representation of a peptide containing a disulfide bridge exposed to trypsin digestion and then undergoing P elimination in the presence of heat or reduction.

[0013] Figure 5 shows a representative charge electropherogram (CE) of composition M281; primary isoform eluted between 3.03 and 3.13 min. and secondary isoform eluted between 3.23 and 3.31 min.

[0014] Figure 6 shows representative masses of isolated sample comprising secondary isoform (shown in Figure 5, with the fraction eluted between 3.23 and 3.31 min.) after analysis by microchip zone electrophoresis separation with direct ionization electrospray mass spectrometry.

[0015] Figure 7 shows a schematic flowchart for a method comprising separating the compositions by electrophoresis in Petition 870260064109, dated 06 / 29 / 2026, page 17 / 104 6 / 28 SDS-PAGE gel, isolate the select size variants in each composition, cut the SDS-PAGE gel pages, digest the isolated size variants with trypsin, and analyze the mass distribution of the trypsin-digested size variants by the Nano-LC-MS method.

[0016] Figure 8 shows chemical representations and molecular weights of the expected peptides resulting from trypsin digestion of (A) light-heavy-heavy-light chain (LC-HC-LC); (B) heavy-heavy-light chain (HC-HC-LC); (C) heavy-heavy-light chain, with dehydroalanine replacing Cys219 in the unpaired heavy chain.

[0017] Figure 9 shows the quantification of disulfide bonds between LC-HC-HC-LC chains (data shown in blue) and HC-HCLC chains (data shown in orange) evaluated for isolated compositions containing LC-HC-LC-HC, Cys-A, DeHA-A and Cys-HC-HC. DETAILED DESCRIPTION

[0018] The present invention discloses innovative compositions comprising an antibody directed to the human neonatal Fc receptor (FcRN). These compositions are useful, for example, to promote the clearance of autoantibodies in an individual, to suppress antigen presentation in an individual, to block an immune response (e.g., to block an activation of the immune response based on immune complexes in an individual), or to treat immunological diseases (e.g., autoimmune diseases) in an individual. This document discloses compositions containing the aforementioned isolated antibody and one or more size variants, wherein the final composition contains at least 80% of the total protein content comprising the fully assembled light-heavy-heavy-light (LC-HC-HC-LC) chain having a molecular weight of approximately 140,000 to 143,000 (e.g., 141,750 to 141,800) Da and up to 5% (45, 3%, 2%, 1%, 0.8%) of the total content. Petition 870260064109, dated 06 / 29 / 2026, page 18 / 104 7 / 28 of proteins comprising select size variants of lower molecular weight (e.g., 118,000 to 120,000 Da). Anti-FCRN antibodies

[0019] The antibodies that can be formulated as described in this document include an antibody that has the light chain sequence QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAP KLMIYGDSERPS GVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGT KVTVLGQPKA APSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAG VETTTPSKQSN NKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1) and the heavy chain sequence EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGL EWVSSIGASGS QTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGD SYWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN SGALTSGVHTF PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP KSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF NWYVDGVEVH NAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKG QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVL DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS Petition 870260064109, dated 06 / 29 / 2026, page 19 / 104 8 / 28 PG (SEQ ID NO: 2).

[0020] Variants of this antibody may also be formulated as described in this document. Such variants include: an antibody having a light chain sequence of a variant with SEQ ID NO:1 having substitutions or deletions of 1 to 5 single amino acids (and preferably comprising CDR sequences of SEQ ID NO: 3 to 5) and a heavy chain sequence of a variant with SEQ ID NO:24 having substitutions or deletions of 1 to 5 single amino acids (and preferably comprising CDR sequences of SEQ ID NO: 6 to 8). Antibodies that are composed of a variant with SEQ ID NO:1 and a variant with SEQ ID NO:4 preferably retain the CDR sequences M281: TGTGSDVGSYNLVS (light chain CDR1; SEQ ID NO: 3); GDSERPS (light chain CDR2; SEQ ID NO: 4); SSYAGSGIYV (light chain CDR3; SEQ ID NO: 5); TYAMG (heavy chain CDR1; SEQ ID NO: 6); SIGASGSQTRYADS (heavy chain CDR2; SEQ ID NO: 7); and LAIGDSY (heavy chain CDR3; SEQ ID NO: 8).

[0021] In some cases, the light chain has a sequence that has at least 90%, 95%, or 98% identity to: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAP KLMIYGD SERPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYV FGTGTKVTVLG QPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSP VKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGS TVEKTVAPTECS (SEQ ID NO: 1).

[0022] In some cases, the heavy chain has a sequence that has at least 90%, 95%, or 98% identity to: EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGL EWVSSIG Petition 870260064109, dated 06 / 29 / 2026, page 20 / 104 9 / 28 ASGSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARL AIGDSYWGQ GTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSG VHTFP AVLQS SGLYSLS S VVTVPSS SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED PEVKFNWYVD GVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTI SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKT TPPVLDSDGSFFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPG (SEQ ID NO: 2).

[0023] In some cases, the antibody includes amino acid substitutions, additions, and / or deletions in the constant regions (e.g., Fc region) of the antibody that, for example, lead to decreased effector function, e.g., decreased complement-dependent cytolysis (CDC), antibody-dependent cell-mediated cytolysis (ADCC), and / or antibody-dependent cell-mediated phagocytosis (ADCP), and / or decreased B cell death. The constant regions are not directly involved in the binding of an antibody to its target, but exhibit various effector functions, such as the antibody's participation in antibody-dependent cellular toxicity. In some cases, the antibody is characterized by decreased binding (i.e., absence of binding) to human complement factor Clq and / or human Fc receptor on natural killer (NK) cells. In other cases, the antibody is characterized by decreased binding (i.e., absence of binding) to FcyRI, FcyRIIA, and / or FcyRIIIA.To alter or reduce an antibody-dependent effector function, such as CDC, ADCC, ADCP, and / or B cell death, antibodies can... Petition 870260064109, dated 06 / 29 / 2026, p. 21 / 104 10 / 28 being of the IgG class and containing one or more amino acid substitutions E233, L234, G236, D265, D270, E318, K320, K322, A327, A330, P331 and / or P329 (EU numbering (Edelman et al., Proc. Natl. Acad. USA, 63:78 to 85 (1969)), in full unless otherwise indicated). In some cases, the antibody has the L234A / L235A or D265A / N297A mutations. In some cases, the antibody contains the A297N amino acid substitution, relative to the SEQ ID sequences NO:2, so that the antibody is altered to a glycosylated form of Fc (i.e., complement binding Clq), whereas antibodies with N297A (e.g., SEQ ID NO:2) have very little binding to complement or Fc receptors (i.e., binding to complement Clq), which indicates low CDC potential.In some cases, the amino-terminal Gin, in the light chain, is pyroGin. Vectors, Host Cells, and Antibody Production

[0024] Anti-FcRn antibodies can be produced from a host cell. A host cell refers to a vehicle that includes the necessary cellular components, for example, organelles, needed to express the polypeptides and constructs described herein from their corresponding nucleic acids. Nucleic acids can be included in nucleic acid vectors, which can be introduced into the host cell by conventional techniques known in the art (e.g., transformation, transfection, electroporation, calcium phosphate precipitation, direct microinjection, infection, etc.). The choice of nucleic acid vectors depends, in part, on the host cells to be used. Generally, the preferred host cells are Petition 870260064109, dated 06 / 29 / 2026, page 22 / 104 11 / 28 prokaryotic (e.g., bacterial) or eukaryotic (e.g., mammalian) origin. Nucleic acid vector and host cell construction

[0025] A nucleic acid sequence encoding the amino acid sequence of an anti-FcRn antibody can be prepared by a variety of methods known in the art. These methods include, but are not limited to, oligonucleotide-mediated (or site-directed) mutagenesis and PCR mutagenesis. A nucleic acid molecule encoding an anti-FcRn antibody can be obtained using standard techniques, for example, gene synthesis. Alternatively, a nucleic acid molecule encoding a wild-type anti-FcRn antibody can be mutated to contain specific amino acid substitutions using standard techniques in the art, for example, QuikChange™ mutagenesis. Nucleic acid molecules can be synthesized using a nucleotide synthesizer or PCR techniques.

[0026] Nucleic acid sequences encoding an anti-FcRn antibody can be inserted into a vector capable of replicating and expressing the nucleic acid molecules in prokaryotic or eukaryotic host cells. Many vectors are available in the art and can be used. Each vector can contain several components that can be adjusted and optimized for compatibility with the specific host cell. For example, vector components may include, but are not limited to, an origin of replication, a selection marker gene, a promoter, a ribosomal binding site, a signal sequence, the nucleic acid sequence encoding the protein of interest, and a transcription termination sequence.

[0027] Mammalian cells can be used as cells Petition 870260064109, dated 06 / 29 / 2026, page 23 / 104 12 / 28 host cells. Examples of mammalian cell types include, but are not limited to, human embryonic kidney (HEK) (e.g., HEK293, HEK 293F), Chinese hamster ovary (CHO), HeLa, COS, PC3, Vero, MC3T3, NS0, Sp2 / 0, VERY, BHK, MDCK, W138, BT483, Hs578T, HTB2, BT20, T47D, NS0 (a murine myeloma cell line that does not endogenously produce any immunoglobulin chains), CRL7O3O cells, and HsS78Bst cells. In another container, E. coli cells can be used as host cells. Examples of E. coli strains include, but are not limited to, E. coli 294 (ATCC® 31,446), E. coli X 1776 (ATCC® 31,537), E. coli BL21 (DE3) (ATCC® BAA-1025), and E. coli RV308 (ATCC® 31,608). Different host cells possess characteristic and specific mechanisms for post-translational processing and modification of protein products.Appropriate cell lines or host systems may be selected to ensure proper modification and processing of the expressed anti-FcRn antibody. The expression vectors described above may be introduced into appropriate host cells using conventional techniques in the art, for example, transformation, transfection, electroporation, calcium phosphate precipitation, and direct microinjection. Once the vectors are introduced into host cells for protein production, the host cells are cultured in modified conventional nutrient media, as appropriate, to induce promoters, select transformers, or amplify genes encoding the desired sequences. Methods for therapeutic protein expression are known in the art; see, for example, Paulina Baibas, Argelia Lorence (eds.) Recombinant Gene Expression: Reviews and Protocols (Methods in Molecular Biology), Humana Press; 2nd ed.2004 (July 20, 2004) and Vladimir Voynov and Justin A. Caravella (eds.) Therapeutic Proteins: Methods and Protocols (Methods in Molecular Biology). Petition 870260064109, dated 06 / 29 / 2026, p. 24 / 104 13 / 28 Humana Press; 2nd ed. 2012 (June 28, 2012). PRODUCTION, RECOVERY AND PURIFICATION OF PROTEINS

[0028] Host cells used to produce an anti-FcRn antibody can be cultured in media known in the art and suitable for culturing the selected host cells. Examples of suitable media for mammalian host cells include Minimum Essential Medium (MEM), Dulbecco's Modified Eagle Medium (DMEM), Expi293™ Expression Medium, DMEM, supplemented with fetal bovine serum (FBS) and RPMI-1640. Examples of suitable media for bacterial host cells include Luria broth (LB) plus necessary supplements, such as a selection agent, for example, ampicillin. Host cells are cultured at suitable temperatures, such as from about 20°C to about 39°C, for example, 25°C to about 37°C, preferably 37°C, and CO2 levels such as 5 to 10% (preferably 8%). The pH of the medium is generally around 6.8 to 7.4, for example, 7.0, depending mainly on the host organism.If an inducible promoter is used in the expression vector, protein expression will be induced under conditions suitable for promoter activation.

[0029] Protein recovery typically involves disrupting the host cell, usually by means such as osmotic shock, sonication, or lysis. Once the cells are disrupted, cellular debris can be removed by centrifugation or filtration. Proteins can be further purified. An anti-FcRn antibody can be purified by any method known in the art of protein purification, for example, by protein A affinity, by other chromatography (e.g., ion exchange, affinity, and size exclusion column chromatography), centrifugation, differential solubility, or by any other standard technique for protein purification (see Process Scale Purification of Petition 870260064109, dated 06 / 29 / 2026, page 25 / 104 14 / 28 Antibodies, Uwe Gottschalk (ed.) John Wiley & Sons, Inc., 2009). In some cases, an anti-FcRn antibody can be conjugated to marker sequences, such as a peptide, to facilitate purification. An example of a marker amino acid sequence is a hexahistidine peptide (His-tag), which binds to a nickel-functionalized agarose affinity column with micromolar affinity. Other useful peptide markers for purification include, but are not limited to, the hemagglutinin marker HA, which corresponds to an epitope derived from the influenza hemagglutinin protein. TREATMENT METHODS AND INDICATIONS

[0030] Blocking human FcRN by pharmaceutical compositions containing anti-fcRN antibodies described in this document may have therapeutic benefit in diseases driven by IgG autoantibodies. The ability of FcRN blockade to induce catabolism and removal of general IgG from various autoantibody species, small circulating metabolites, or lipoproteins offers a method to expand the utility and accessibility of an autoantibody removal strategy for patients with autoantibody-driven autoimmune disease pathology. Without adhering to any theory, the dominant mechanism of action of an anti-fcRN antibody may be to increase the catabolism of circulating pathogenic autoantibodies and decrease autoantibody and immune complex deposition in affected tissues.

[0031] Pharmaceutical compositions are useful for promoting the catabolism and clearance of pathogenic antibodies, for example, IgG and IgG autoantibodies, in an individual, for reducing the immune response, for example, for blocking the activation of immune responses based on immune complexes in an individual, and for treating immunological conditions or diseases in an individual. In particular, pharmaceutical compositions are useful for reducing or treating Petition 870260064109, dated 06 / 29 / 2026, page 26 / 104 15 / 28 an activation based on immune complexes of an acute or chronic immune response. The acute immune response may be activated by a medical condition selected from the group consisting of pemphigus vulgaris, lupus nephritis, myasthenia gravis, Guillain-Barré syndrome, antibody-mediated rejection, antiphospholipid antibody syndrome (e.g., catastrophic antiphospholipid antibody syndrome), immune complex-mediated vasculitis, glomerulitis, channelopathy, neuromyelitis optica, autoimmune hearing loss, idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), immune neutropenia, dilated cardiomyopathy, and serum sickness.The chronic immune response can be activated by a selected medical condition from the group consisting of chronic inflammatory demyelinating polyneuropathy (CIDP), systemic lupus, a chronic form of a disorder indicated for acute treatment, reactive arthropathies, primary biliary cirrhosis, ulcerative colitis, and vasculitis associated with antineutrophil cytoplasmic antibody (ANCA).

[0032] In some cases, pharmaceutical compositions are useful for reducing or treating an immune response triggered by an autoimmune disease. Autoimmune disease can be selected from the group consisting of alopecia areata, ankylosing spondylitis, antiphospholipid syndrome, Addison's disease, hemolytic anemia, autoimmune hepatitis, hepatitis, Behcet's disease, bullous pemphigoid, cardiomyopathy, dermatitis herpetiformis, chronic fatigue immune dysfunction syndrome, chronic inflammatory demyelinating polyneuropathy, Churg-Strauss syndrome, cicatricial pemphigoid, limited scleroderma (CREST syndrome), cold agglutinin disease, Crohn's disease, dermatomyositis, discoid lupus, essential mixed cryoglobulinemia, fibromyalgia, fibromyositis, Graves' disease, Hashimoto's thyroiditis, hypothyroidism, inflammatory bowel disease, autoimmune lymphoproliferative syndrome, idiopathic pulmonary fibrosis, nephropathy of Petition 870260064109, dated 06 / 29 / 2026, page 27 / 104 16 / 28 IgA, insulin-dependent diabetes, juvenile arthritis, lichen planus, lupus, Meniere's disease, mixed connective tissue disease, multiple sclerosis, pernicious anemia, polyarteritis nodosa, polychondritis, polyglandular syndromes, polymyalgia rheumatica, polymyositis, primary agammaglobulinemia, primary biliary cirrhosis, psoriasis, Raynaud's phenomenon, Reiter's syndrome, rheumatic fever, rheumatoid arthritis, sarcoidosis, scleroderma, Sjögren's syndrome, stiff-man syndrome, Takayasu's arteritis, temporal arteritis, ulcerative colitis, uveitis, vitiligo, and Wegener's granulomatosis.

[0033] In particular, the pharmaceutical compositions are useful for reducing or treating an immune response triggered by systemic lupus erythematosus, antiphospholipid syndrome, pemphigus vulgaris / bullous pemphigoid, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, myasthenia gravis or neuromyelitis optica.

[0034] In some cases, pharmaceutical compositions are useful for decreasing or reducing the risk of developing anemia in the fetus. In some cases, pharmaceutical compositions are useful for decreasing or avoiding the need for IUT (intrauterine transfusion). In some cases, pharmaceutical compositions and methods are useful for decreasing or avoiding the need for prenatal PP+ IVIg, postnatal transfusion, IVIg and / or phototherapy.

[0035] In some cases, pharmaceutical compositions are useful for reducing or treating an immune response triggered by an autoimmune disease. The autoimmune disease may be selected from the group consisting of alopecia areata, ankylosing spondylitis, antiphospholipid syndrome, Addison's disease, hemolytic anemia, autoimmune hepatitis, hepatitis, Behcet's disease, bullous pemphigoid, cardiomyopathy, dermatitis herpetiformis, chronic fatigue immune dysfunction syndrome, demyelinating polyneuropathy Petition 870260064109, dated 06 / 29 / 2026, page 28 / 104 17 / 28 chronic inflammatory disease, Churg-Strauss syndrome, cicatricial pemphigoid, limited scleroderma (CREST syndrome), cold agglutinin disease, Crohn's disease, dermatomyositis, discoid lupus, essential mixed cryoglobulinemia, fibromyalgia, fibromyositis, Graves' disease, Hashimoto's thyroiditis, hypothyroidism, inflammatory bowel disease, autoimmune lymphoproliferative syndrome, idiopathic pulmonary fibrosis, IgA nephropathy, insulin-dependent diabetes, juvenile arthritis, lichen planus, lupus, Meniere's disease, mixed connective tissue disease, multiple sclerosis, pernicious anemia, polyarteritis nodosa, polychondritis, polyglandular syndromes, polymyalgia rheumatica, polymyositis, primary agammaglobulinemia, primary biliary cirrhosis, psoriasis, Raynaud's phenomenon, Reiter's syndrome, rheumatic fever, rheumatoid arthritis, sarcoidosis, scleroderma, Sjögren's syndrome, stiff man syndrome, Takayasu arteritis, temporal arteritis, ulcerative colitis, uveitis,vitiligo and Wegener's granulomatosis.

[0036] In some cases, pharmaceutical compositions are useful for reducing or treating an immune response in a fetus or neonate. In some cases, pharmaceutical compositions and methods are useful for reducing or treating an immune response in a fetus or neonate triggered by an autoimmune disease in the pregnant woman.

[0037] In particular, the pharmaceutical compositions are useful for reducing or treating an immune response triggered by systemic lupus erythematosus, antiphospholipid syndrome, pemphigus vulgaris / bullous pemphigoid, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, myasthenia gravis, or neuromyelitis optica. In some cases, the pharmaceutical compositions are useful for reducing or treating an immune response in a fetus or neonate. In some cases, the pharmaceutical compositions and methods are useful for reducing or treating an immune response triggered by systemic lupus erythematosus, antiphospholipid syndrome, pemphigus Petition 870260064109, dated 06 / 29 / 2026, page 29 / 104 18 / 28 vulgaris / bullous pemphigoid, vasculitis associated with antineutrophil cytoplasmic antibody (ANCA), myasthenia gravis, or neuromyelitis optica in pregnant women.

[0038] The pharmaceutical compositions are useful in methods of decreasing the transport of pathogenic antibodies (e.g., transport of pathogenic maternal IgG antibodies) across the placenta of a pregnant woman, which increases the catabolism of pathogenic antibodies in a pregnant woman and treats an antibody-mediated intensification of viral disease in a fetus or newborn by administering to a pregnant woman an isolated antibody that binds to human FcRN. Diseases and disorders that may benefit from FcRN inhibition by the pharmaceutical compositions described herein include diseases and disorders in a fetus and / or neonate caused by the transfer of pathogenic maternal antibodies (e.g., pathogenic maternal IgG antibodies) across the placenta of a pregnant woman to the fetus and / or neonate.

[0039] In some cases, the diseases and disorders that may benefit from treatment with the pharmaceutical compositions described in this document are fetal and neonatal alloimmune and / or autoimmune disorders. Fetal and neonatal alloimmune disorders are disorders in a fetus and / or neonate caused by pathogenic antibodies in the pregnant woman. The pathogenic antibodies in the pregnant woman may attack the fetus's antigens (e.g., fetal antigens inherited from the fetus's father), causing the fetus or newborn to have a fetal and neonatal alloimmune and / or autoimmune disorder.

[0040] Examples of fetal and neonatal alloimmune and / or autoimmune disorders that may be treated include, but are not limited to, fetal and neonatal alloimmune thrombocytopenia (FNAIT), hemolytic disease of the fetus and newborn (HDFN), alloimmune panthrombocytopenia, congenital heart block, fetal arthrogryposis, myasthenia gravis Petition 870260064109, dated 06 / 29 / 2026, p. 30 / 104 19 / 28 neonatal, neonatal autoimmune hemolytic anemia, neonatal antiphospholipid syndrome, neonatal polymyositis, dermatomyositis, neonatal lupus, neonatal scleroderma, Bechet's disease, neonatal Graves' disease, neonatal Kawasaki disease, neonatal autoimmune thyroid disease, and neonatal type I diabetes mellitus.

[0041] In some cases, the diseases and disorders that may benefit from treatment with the pharmaceutical compositions described in this document are viral diseases, in which antibodies facilitate viral entry into host cells, leading to an increase or intensification of infectivity in the cells, for example, antibody-mediated intensification of viral disease. In some cases, an antibody may bind to a viral surface protein, and the antibody / virus complex may bind to an FCrN on a cell surface through antibody-receptor interaction. Subsequently, the antibody / virus complex may internalize into the cell. For example, a virus may gain entry into the cells and / or tissues of a fetus through the formation of a complex with a maternal IgG antibody.A maternal IgG antibody can bind to a viral surface protein, and the IgG / virus complex can bind to an FcrN on placental syncytiotrophoblasts, which then transfer the complex to the fetus.

[0042] In some cases, the pharmaceutical compositions described herein may be used to treat antibody-mediated intensification of viral disease. In some cases, viral diseases that are intensified by pathogenic antibodies (e.g., pathogenic IgG antibodies) include, but are not limited to, viral diseases caused by alpha virus infection, flavivirus infection, Zika virus infection, Chikungunya virus infection, Ross River virus infection, severe acute respiratory syndrome coronavirus infection, East respiratory syndrome. Petition 870260064109, dated 06 / 29 / 2026, p. 31 / 104 20 / 28 Medium severity, avian influenza infection, influenza virus infection, human respiratory syncytial virus infection, Ebola virus infection, yellow fever virus infection, dengue virus infection, human immunodeficiency virus infection, respiratory syncytial virus infection, hantavirus infection, Getah virus infection, Sindbis virus infection, Bunyamwera virus infection, West Nile virus infection, Japanese encephalitis B virus infection, rabbitpox virus infection, lactate dehydrogenase elevated virus infection, reovirus infection, rabies virus infection, foot-and-mouth disease virus infection, porcine reproductive and respiratory syndrome virus infection, simian hemorrhagic fever virus infection, equine infectious anemia virus infection, caprine arthritis virus infection, African swine fever virus infection, lentivirus infection, papovavirus BK infection.Murray Valley encephalitis virus infection, enterovirus infection, cytomegalovirus infection, pneumovirus infection, morbillivirus infection, and measles virus infection.

[0043] Blocking human FcRn with anti-FcRn antibodies may have therapeutic benefit in diseases that are driven by pathogenic antibodies (e.g., pathogenic IgG antibodies). The ability of FcRn blockade to induce catabolism and overall pathogenic removal of multiple species of pathogenic antibodies, without disturbing serum albumin, small circulating metabolites, or lipoproteins, offers a method to expand the utility and accessibility of a pathogenic antibody removal strategy for patients with pathogenic antibody-driven autoimmune disease pathology. Although not linked by theory, the dominant mechanism of action of an anti-FcRn antibody may be to increase the catabolism of circulating pathogenic antibodies and decrease the deposition of pathogenic antibodies. Petition 870260064109, dated 06 / 29 / 2026, page 32 / 104 21 / 28 immunological complexes in the affected tissues.

[0044] The pharmaceutical compositions described in this document may be administered to a pregnant woman who has or is at risk of having a medical condition that activates an immune response in the pregnant woman. In some cases, the pregnant woman may have had a medical condition in the past that activated an immune response in the pregnant woman. In some cases, the pregnant woman has a history of having had a previous fetus or neonate with fetal and neonatal alloimmune and / or autoimmune disorders. In some cases, the anti-FcRn antibodies described in this document may be administered to a pregnant woman if a pathogenic antibody associated with an immune disease is detected in a biological sample (e.g., a blood or urine sample) obtained from the pregnant woman. In some cases, the pathogenic antibody detected in the pregnant woman's biological sample is known to bind to a fetal antigen in the pregnant woman (e.g., an antigen that the fetus inherited from the fetus's father).

[0045] In some cases, pharmaceutical compositions may be administered to a person planning to become pregnant who has or is at risk of having a medical condition that activates an immune response in the pregnant woman and / or who has had, in the past, a medical condition that activated an immune response in the pregnant woman. In some cases, the person is planning to become pregnant and has a history of having had a previous fetus or neonate that presented with a fetal and neonatal alloimmune and / or autoimmune disorder. In some cases, the anti-FcRn antibodies described in this document may be administered to a person planning to become pregnant whose biological sample contains a pathogenic antibody associated with an immunological disease.

[0046] In some cases, the pharmaceutical compositions described in this document may be administered to a person (for example, a pregnant woman) to reduce or treat an activation based Petition 870260064109, dated 06 / 29 / 2026, p. 33 / 104 22 / 28 in immune complexes of an acute or chronic immune response in a person. The acute immune response may be triggered by a medical condition (e.g., pemphigus vulgaris, lupus nephritis, myasthenia gravis, Guillain-Barré syndrome, antibody-mediated rejection, catastrophic antiphospholipid antibody syndrome, immune complex-mediated vasculitis, glomerulitis, channelopathy, neuromyelitis optica, autoimmune hearing loss, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, immune neutropenia, dilated cardiomyopathy, serum sickness, chronic inflammatory demyelinating polyneuropathy, systemic lupus, reactive arthropathies, primary biliary cirrhosis, ulcerative colitis, or antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis).

[0047] In some cases, the redaction described in this document may be administered to an individual (for example, a pregnant woman) to reduce or treat an immune response triggered by an autoimmune disease.Autoimmune disease can include, for example, alopecia areata, ankylosing spondylitis, antiphospholipid syndrome (e.g., antiphospholipid antibody syndrome), epidermolysis bullosa, membranous nephropathy, Addison's disease, hemolytic anemia, warm autoimmune hemolytic anemia (WaiHa), antifactorial antibodies, heparin-induced thrombocytopenia (HICT), sensitized transplant, autoimmune hepatitis, hepatitis, Behcet's disease, bullous pemphigoid, cardiomyopathy, dermatitis herpetiformis, chronic fatigue immune dysfunction syndrome, chronic inflammatory demyelinating polyneuropathy, Churg-Strauss syndrome, cicatricial pemphigoid, limited scleroderma (CREST syndrome), cold agglutinin disease, Crohn's disease, dermatomyositis, discoid lupus, essential mixed cryoglobulinemia, fibromyalgia, fibromyositis, Graves' disease, thyroiditis of Hashimoto's disease, hypothyroidism, inflammatory bowel disease, autoimmune lymphoproliferative syndrome, fibrosis. Petition 870260064109, dated 06 / 29 / 2026, page 34 / 104 23 / 28 idiopathic pulmonary disease, IgA nephropathy, insulin-dependent diabetes, juvenile arthritis, lichen planus, lupus, Meniere's disease, mixed connective tissue disease, multiple sclerosis, pernicious anemia, polyarteritis nodosa, polychondritis, polyglandular syndromes, polymyalgia rheumatica, polymyositis, primary agammaglobulinemia, primary biliary cirrhosis, psoriasis, Raynaud's phenomenon, Reiter's syndrome, rheumatic fever, rheumatoid arthritis, sarcoidosis, scleroderma, Sjögren's syndrome, stiff man syndrome, Takayasu arteritis, temporal arteritis, ulcerative colitis, uveitis, vitiligo, or Wegener's granulomatosis. EXAMPLES

[0048] The invention is further described in the following examples, which do not limit the scope of the invention described in the claims.

[0049] The following materials and methods were used in Examples are presented in this document. MATERIALS

[0050] M281 Production: The cell culture producing the light and heavy chains was clarified by centrifugation and filtration, followed by virus inactivation with detergent treatment. After virus inactivation, the material was applied to a protein A column to remove process-related impurities (e.g., host cell proteins (HCPs), DNA, and media additives). The eluate was applied to an anion exchange column and a virus removal filter. Further filtration through a 30 kDa nominal molecular weight cutoff polyethersulfone membrane was performed after virus removal and before concentration and diafiltration, using a 25 mM sodium phosphate and 25 mM sodium chloride buffer at pH 6.5. The material was formulated by adding trehalose at a final concentration of 8.7% w / w and polysorbate 80 at a final concentration of 0.01% w / v. M281 is diluted to a target of Petition 870260064109, dated 06 / 29 / 2026, page 35 / 104 24 / 28 mg / mL (range 27 to 33 mg / mL) with formulation buffer (25 mM sodium phosphate, 25 mM sodium chloride, 8.7% trehalose, 0.01% w / v polysorbate 80, pH 6.5). EXAMPLE 1. DETECTION OF SIZE VARIANT SPECIES

[0051] A size variant species was reproductively detected in compositions produced using the methods described in this document and containing M281 antibody analyzed by unreduced capillary electrophoresis with SDS (NR CE-SDS). RESULTS.

[0052] The M281 compositions were prepared and analyzed by NR CE-SDS. Electrophoretogram readings of the M281 compositions analyzed by NR CE-SDS showed two separate peaks – one peak with a retention time of 26 to 27 min and the other peak with a retention time of 27.5 to 29 min (Figure 1). The latter peak corresponded to the fully assembled light-heavy-heavy-light chain (LC-HC-HC-LC), while the former peak corresponded to a size-variant molecule with lower weight compared to the heavy-heavy-light chain (designated HC-HC-LC or HHL). The level of the size-variant molecule, as detected by NR CE-SDS, remained at approximately 4.0 to 4.5 percent of the total protein content during all downstream processing steps, GMP DS and DP batches, and during the stability study (data not shown). Furthermore, there was no significant change in the level of this size variant, as detected by NR CE-SDS, during the scaling from the 250 L pilot level to the 2000 L GMP scale. Levels of this size variant.The formation of the size variant in the M281 compositions increased when the compositions were exposed to denaturing conditions, such as increased incubation temperature (e.g., from 37 °C to 70 °C), during sample preparation, or before CE-SDS analysis. Petition 870260064109, dated 06 / 29 / 2026, page 36 / 104 25 / 28 EXAMPLE 2. CHARACTERIZATION OF MOLECULAR WEIGHTS FOR SIZE-VARIANT SPECIES DETECTED IN M281 COMPOSITIONS

[0053] To determine the molecular mass of size-variant species in M281 compositions, the M281 compositions were analyzed by three methods, which included hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC LCMS), microchip zone electrophoresis separation with direct ionization mass spectrometry by electrospray spectroscopy, and non-reduced tryptic digestion of proteins separated by gel electrophoresis followed by nanoliquid chromatography coupled to mass spectrometry. RESULTS.

[0054] Analysis of the M281 compositions by HILIC LC-MS revealed a peak centered at a retention time of 12.5 min in the UV chromatogram of the HILIC separation (Figure 2A), which resolved by mass spectrometry into two species – one peak centered at a retention time of 12.42 min and the other centered at a retention time of 12.68 min (Figure 2B). The molecular mass distribution at the retention time peaks of 12.42 min and 12.68 min was determined by deconvolution of the mass spectra for both peaks. Deconvolution of the mass spectrum of the species at the peak, at a retention time of 12.42 min, revealed several size variants, including a dominant species of 119.277 Da (Figure 3A). The aforementioned dominant species of 119.277 Da was close to the theoretical mass of 119.177 Da for a heavy-heavy-light chain (denominated HC-HC-LC or HHL), in which dehydroalanine replaces cysteine ​​at position 219 in the unpaired heavy chain, an expected product of disulfide bond elimination (Figure 4). The deconvolution of the mass spectrum of the species at the peak, over time. Petition 870260064109, dated 06 / 29 / 2026, page 37 / 104 26 / 28 retention time of 12.68 min., revealed several size variants including a dominant species of 119.329 Da (Figure 3B). The aforementioned dominant species of 119.329 Da was close to the theoretical mass of 119.329 Da for a heavy-heavy-light chain (denominated HC-HC-LC or HHL) with an unpaired cysteinylated heavy chain.

[0055] To further characterize the molecular weights of the size-variant species in M281 compositions, the M281 compositions were analyzed by microchip zone electrophoresis (MZE) separation with direct electrospray ionization mass spectrometry (ESI-MS). The MZE separation electropherogram showed a secondary acidic species with a migration time of around 3.23 min. (Figure 5). The deconvolution of the species' mass spectrum, at the peak eluting around 3.23 min., revealed several size variants, including two dominant species with molecular masses of 119,178 Da and 119,332 Da. The dominant species mentioned above was close to the theoretical mass of 119,177 Da for a heavy-heavy-light chain (HHL), where dehydroalanine replaces cysteine ​​at position 219 in the unpaired heavy chain, and 119,329 Da for a heavy-heavy-light chain (denoted HC-HC-LC or HHL), with a cysteinylated unpaired heavy chain, respectively.

[0056] To further characterize the molecular weights of the size-variant species in the M281 compositions, the M281 compositions were separated by SDSPAGE gel electrophoresis, and two bands corresponding to the light-heavy-heavy-light chain and the heavy-heavy-light chain were cut from the gel (as detailed in Figure 7). The isolated gel fragments were subjected to non-reduced tryptic gel digestion, and the resulting digestion fragments were analyzed by nanoliquid chromatography. Petition 870260064109, dated 06 / 29 / 2026, page 38 / 104 27 / 28 coupled to mass spectrometry (as detailed in Figure 7). The expected tryptic digested peptides and molecular masses are shown in Figure 8, for the light-heavy-heavy-light chain, the heavy-heavy-light chain with cysteinylated unpaired heavy chain, and where the heavy-heavy-light chain with dehydroalanine replaces cysteine ​​at position 219 (of SEQ ID NO:2) in the unpaired heavy chain. The tryptic digested peptides corresponding to the last two species were detected as dominant species in the SDS-PAGE gel electrophoresis band corresponding to the heavy-heavy-light chain and as minor species in the SDS-PAGE gel electrophoresis band corresponding to the light-heavy-heavy-light chain band (Table 1 and Figure 9). TABLE 1. PERCENTAGES OF PEAK AREA OF ION CHROMATOGRAM (PEA) EXTRACTED FOR EACH INDIVIDUAL CHARACTERISTIC PEPTIDE, IN RELATION TO THE TOTAL PEAK AREA OF ALL CHARACTERISTIC PEPTIDES DETECTED Characteristic peptide (structure and molecular mass shown in Figure 8) Band removed from SDS-PAGE gel electrophoresis Light-heavy-light chain (denoted LCHC-HC-LC or LHHL) Heavy-heavy-light chain (denoted HC-HCLC or HHL). LC-HC-HC-LC 97.09% 9.22% Cys-A 1.08% 52.43% DeHA-A 1.71% 35.52% Cys-HC-HC 0.12% 2.84%

[0057] In summary, three analytical methods identified the size-variant species in compositions M281 as having molecular masses similar to those of the cysteinyl-heavy chain and the Petition 870260064109, dated 06 / 29 / 2026, page 39 / 104 28 / 28 heavy-heavy-light chain of dehydroalanine.

[0058] In another example, an M281 preparation was prepared and subjected to stability tests by storage at 5 ±3 °C. The protein weight percentage was in the range of 119,150 to 119,350 Da (HHL is shown in Table 2). TABLE 2. PERCENTAGE WEIGHT OF PROTEIN 119.150 to 119.350 OF Time % by weight from 119,150 to 119,350 From Initial 1.0 1 month 1.1 3 months 1.1 Petition 870260064109, dated 06 / 29 / 2026, p. 40 / 104

Claims

1 / 3 CLAIMS 1. Pharmaceutical composition characterized in that it comprises: an antibody (LHHL) comprising a heavy chain comprising the amino acid sequence of SEQ ID NO:2 and a light chain comprising the amino acid sequence of SEQ ID NO:1, wherein the composition comprises a major protein component having a molecular weight of 140,500 to 143,000 Da and a minor protein component having a molecular weight of 119,150 to 119,350 Da, wherein the major component has at least 80% by weight of the protein in the composition, and the minor component has at least 1% by weight of the protein in the composition, provided that the matter to be deferred in patent application BR112021000755-5 is excluded.

2. Pharmaceutical composition, according to claim 1, characterized in that the main protein component has at least 93% protein by weight in the composition.

3. Pharmaceutical composition, according to claim 1, characterized in that the secondary protein component comprises an antibody variant comprising two heavy chains and one light chain.

4. Pharmaceutical composition, according to claim 3, characterized in that the antibody variant comprises an unpaired heavy chain and a paired heavy chain and light chain.

5. Pharmaceutical composition, according to claim 3, characterized in that the antibody variant comprises an unpaired heavy chain comprising a polypeptide comprising the amino acid sequence SEQ ID NO:2, wherein the C, at position 219, is replaced by dehydroalanine.

6. Pharmaceutical composition, according to claim Petition 870260064109, dated 06 / 29 / 2026, page 41 / 104 2 / 3 1, characterized in that the secondary protein component comprises: a) a first antibody variant comprising an unpaired heavy chain and a paired heavy chain and a light chain; and b) a second antibody variant comprising an unpaired heavy chain comprising a polypeptide comprising the amino acid sequence SEQ ID NO: 2 in which the C, at position 219, is replaced by dehydroalanine.

7. Method for preparing a pharmaceutical composition, as defined in claims 1 to 6, characterized in that it comprises: providing a composition with an antibody (LHHL) comprising a heavy chain comprising the amino acid sequence SEQ ID NO:2 and a light chain comprising the amino acid sequence SEQ ID NO:1; determining whether the composition comprises a major protein component having a molecular weight of 145,000 to 160,000 Da and a minor protein component with a molecular weight of 119,150 to 119,350 Da; Combining the composition with one or more pharmaceutically acceptable excipients to prepare the pharmaceutical composition is permitted only if the composition comprises a major protein component having a molecular weight of 145,000 to 160,000 Da and a minor protein component having a molecular weight of 119,150 to 119,350 Da, provided that the subject matter to be deferred in patent application BR112021000755-5 is excluded.

8. Method, according to claim 7, characterized in that the prepared pharmaceutical composition comprises 28 to 32 mg / ml of an antibody (LHHL) comprising a heavy chain comprising the amino acid sequence of SEQ ID NO:2 and a light chain comprising the amino acid sequence of SEQ ID NO:

9.

9. Method according to claim 7, characterized in that the prepared pharmaceutical composition comprises 9 to 11 mg / ml of an antibody comprising a heavy chain comprising the amino acid sequence of SEQ ID NO:24 and a light chain comprising the amino acid sequence of SEQ ID NO:

19.

10. Method according to claim 7, characterized in that it further comprises combining the composition with one or more pharmaceutically acceptable excipients to prepare the pharmaceutical composition only if the major component has at least 90% by weight of protein in the composition, and the minor component has at least 3% by weight of protein in the composition.

11. Method according to claim 7, characterized in that the determining step comprises electrophoresis or chromatography.

12. Method according to claim 7, characterized in that the supply step comprises culture cells expressing the heavy chain and the light chain. Petition 870260064109, dated 06 / 29 / 2026, pp. 43 / 104

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