FcRn antagonist molecules and methods of use thereof

Abstract

The present disclosure provides populations of FcRn antagonist molecules, mixtures of these populations, and methods of using these populations to reduce serum IgG autoantibody levels in a subject.

Description

[Technical Field] 【0001】 Related Applications This application claims priority to U.S. Provisional Patent Application No. 63 / 383,599, filed November 14, 2022, the entire disclosure of each of which is incorporated herein by reference. 【0002】 Sequence Listing Reference This application contains a Sequence Listing, which has been submitted electronically in ST.26 format and is incorporated herein by reference in its entirety (a copy of said ST.26, created on November 7, 2023, is designated "404373_T2213WO.xml" and is 39,782 bytes in size). 【0003】 The present disclosure relates to FcRn antagonist molecules, compositions comprising these FcRn antagonist molecules, and methods of reducing serum IgG antibody (e.g., autoantibody) levels in a subject using these FcRn antagonist molecules and compositions. [Background technology] 【0004】 It is estimated that over 2.5% of the human population is affected by autoantibody-driven autoimmune diseases in which autoreactive antibodies are directly pathogenic. The half-life of IgG in serum is extended relative to the serum half-life of other plasma proteins (Roopenian et al., J. Immunology 170:3528 (2003); Junghans and Anderson, Proc. Natl. Acad. Sci. USA 93:5512 (1996)). This long half-life is due in part to the binding of the Fc region of IgG to the Fc receptor, FcRn. Although FcRn was originally characterized as a neonatal transport receptor for maternal IgG, it also functions in adults to protect IgG from degradation. FcRn binds pinocytosed IgG and protects it from transport to degradative lysosomes by recycling it back to the extracellular compartment. This recycling is facilitated by the pH-dependent binding of IgG to FcRn, in which the IgG / FcRn interaction is stronger at acidic endosomal pH than at extracellular physiological pH. 【0005】 When the serum concentration of IgG reaches a level that exceeds the available FcRn molecules, unbound IgG is not protected from degradation mechanisms and, as a result, has a reduced serum half-life. Thus, inhibiting IgG binding to FcRn reduces the serum half-life of IgG by preventing IgG endosomal recycling. Therefore, agents that antagonize IgG binding to FcRn may be useful for regulating, treating, or preventing antibody-mediated disorders, such as autoimmune diseases, inflammatory diseases, and the like. 【0006】 There is a need in the art for agents that antagonize FcRn binding to IgG for use in the treatment of antibody-mediated disorders. Summary of the Invention 【0007】 The present disclosure is directed to novel FcRn antagonist molecules, compositions comprising these FcRn antagonist molecules, and methods for reducing serum IgG antibody (e.g., autoantibody) levels in a subject using these FcRn antagonist molecules and compositions. Also provided herein are nucleic acids encoding the FcRn antagonist molecules, as well as vectors, host cells, production methods, and methods for using them in the treatment of IgG antibody-mediated disorders. The FcRn antagonist molecules provided herein are particularly advantageous in that they are all capable of rapidly reducing serum IgG antibody levels in a subject and exhibit long-term stability in aqueous formulations. 【0008】 The present disclosure provides a composition comprising a population of FcRn antagonist molecules, wherein at least a portion of the FcRn antagonist molecules in the population consist of a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains consist of SEQ ID NO: 1, with the proviso that the population is not a homogeneous population of homodimeric FcRn antagonist molecules in which the amino acid sequences of both the first and second Fc domains consist of SEQ ID NO: 2, 3, 20, or 21. In some embodiments, each FcRn antagonist molecule in the population consists of a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains consist of SEQ ID NO: 1. 【0009】 In some embodiments, the amino acid sequences of the first and second Fc domains consist of SEQ ID NO:3 and SEQ ID NO:12, respectively. In some embodiments, the amino acid sequences of the first and second Fc domains consist of SEQ ID NO:3 and SEQ ID NO:9, respectively. In some embodiments, the amino acid sequences of the first and second Fc domains consist of SEQ ID NO:2 and SEQ ID NO:3, respectively. In some embodiments, the amino acid sequences of the first and second Fc domains consist of SEQ ID NO:3 and SEQ ID NO:6, respectively. 【0010】 In some embodiments, the amino acid sequence of the first Fc domain consists of any one of SEQ ID NOs: 2-22, and the amino acid sequence of the second Fc domain consists of any one of SEQ ID NOs: 2-22. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 5. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 6. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 7. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 8. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 9. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 10. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 11. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 12. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 13. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 14. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 15. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 16. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 17. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 18. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 19. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 22. 【0011】 In some embodiments, the population comprises a first subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of both the first and second Fc domains of the FcRn antagonist molecules in the first subpopulation consist of SEQ ID NO: 3; a second subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the second subpopulation consist of SEQ ID NO: 3 and SEQ ID NO: 12, respectively; a third subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the second subpopulation consist of SEQ ID NO: 3 and SEQ ID NO: 12, respectively; a third subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the fourth subpopulation consist of SEQ ID NO: 3 and SEQ ID NO: 9, respectively; a fourth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of both the first and second Fc domains of the FcRn antagonist molecules in the fourth subpopulation consist of SEQ ID NO: 3, and two asparagine residues in each FcRn antagonist molecule in the fourth subpopulation are deaminated; a fifth subpopulation of FcRn antagonist molecules, wherein a fifth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the fifth subpopulation consist of SEQ ID NO:3 and SEQ ID NO:9, respectively, and one asparagine residue in each FcRn antagonist molecule in the fifth subpopulation is deaminated; and a sixth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the sixth subpopulation consist of SEQ ID NO:2 and SEQ ID NO:3, respectively. a seventh subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the seventh subpopulation consist of SEQ ID NO: 2 and SEQ ID NO: 3, respectively, and one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the seventh subpopulation is oxidized; an eighth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of both the first and second Fc domains of the FcRn antagonist molecules in the eighth subpopulation consist of SEQ ID NO: 2;a ninth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the ninth subpopulation consist of SEQ ID NO: 3 and SEQ ID NO: 6, respectively; a tenth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the tenth subpopulation consist of SEQ ID NO: 2 and SEQ ID NO: 3, respectively; a tenth subpopulation in which one methionine residue or one tryptophan residue is oxidized, and an eleventh subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of both the first and second Fc domains of the FcRn antagonist molecules in the eleventh subpopulation consist of SEQ ID NO: 3, and at least one of the eleventh subpopulation in each FcRn antagonist molecule in the eleventh subpopulation is oxidized, two amino acid residues independently selected from a methionine residue and a tryptophan residue. 【0012】 In some embodiments, the population includes 2, 3, 4, 5, 6, 7, 8, 9, 10, or all of the above subpopulations. In some embodiments, the population includes the 7th, 9th, or 11th subpopulation. In some embodiments, the population includes the 7th, 9th, and 11th subpopulations. 【0013】 In some embodiments, the first subpopulation is at least 55% of the population, optionally, the first subpopulation is 60%-70% of the population. In some embodiments, the second subpopulation is 2.5% or less of the population, optionally, the second subpopulation is 1%-2.5% of the population. In some embodiments, the third subpopulation is 2.5% or less of the population, optionally, the third subpopulation is 1%-2.5% of the population. In some embodiments, the fourth subpopulation is 5% or less of the population, optionally, the fourth subpopulation is 2%-5% of the population. In some embodiments, the fifth subpopulation is 10% or less of the population, optionally, the fifth subpopulation is 7%-10% of the population. In some embodiments, the sixth subpopulation is 20% or less of the population, optionally, the sixth subpopulation is 7%-14% of the population. In some embodiments, the seventh subpopulation is 6% or less of the population, optionally, the seventh subpopulation is 1.5%-2.5% of the population. In some embodiments, the eighth subpopulation is 8% or less of the population, optionally, the eighth subpopulation is 3.5%-7.5% of the population. In some embodiments, the ninth subpopulation is 3.5% or less of the population, optionally, the ninth subpopulation is 0.5%-3.5% of the population. In some embodiments, the tenth subpopulation is 1% or less of the population. In some embodiments, the eleventh subpopulation is 1% or less of the population. 【0014】 In some embodiments, at least 97% of the Fc domains in the population, optionally 97% to 99%, comprise an N-glycan at EU position 297. In some embodiments, at least 50%, optionally 50% to 70% of the Fc domains in the population comprise a GOF N-glycan at EU position 297. In some embodiments, at least 20%, optionally 20% to 30% of the Fc domains in the population comprise a GIF N-glycan at EU position 297. In some embodiments, at least 5%, optionally 8% to 10% of the Fc domains in the population comprise a G2F N-glycan at EU position 297. In some embodiments, at least 2%, optionally 2% to 5% of the Fc domains in the population comprise a GO N-glycan at EU position 297. 【0015】 In some embodiments, at least 40%, optionally 40% to 55%, of the population comprises a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G0F N-glycan at EU position 297. In some embodiments, at least 20%, optionally 20% to 25%, of the population comprises a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G1F N-glycan at EU position 297. In some embodiments, at least 10%, optionally 10% to 15%, of the population either comprises a first Fc domain comprising a G1F N-glycan at EU position 297 and a second Fc domain comprising a G1F N-glycan at EU position 297, or comprises a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. In some embodiments, at least 5%, optionally 5% to 10%, of the population comprises a first Fc domain comprising a G1F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. In some embodiments, at least 2%, optionally 2% to 4%, of the population comprises a first Fc domain comprising a G2F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. In some embodiments, at least 4%, optionally 4% to 6%, of the population comprises a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G0 N-glycan at EU position 297. 【0016】 The present disclosure also provides a composition comprising an FcRn antagonist molecule, wherein the FcRn antagonist molecule consists of a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains consist of SEQ ID NO: 1, and wherein at least one Fc domain comprises a G0F N-glycan at EU position 297, a G1F N-glycan at EU position 297, a G2F N-glycan at EU position 297, or a G0 N-glycan at EU position 297. 【0017】 In some embodiments, the first Fc domain comprises a G0F N-glycan at EU position 297 and the second Fc domain comprises a G0F N-glycan at EU position 297. In some embodiments, the first Fc domain comprises a G0F N-glycan at EU position 297 and the second Fc domain comprises a G1F N-glycan at EU position 297. In some embodiments, the first Fc domain comprises a G0F N-glycan at EU position 297 and the second Fc domain comprises a G2F N-glycan at EU position 297. In some embodiments, the first Fc domain comprises a G1F N-glycan at EU position 297 and the second Fc domain comprises a G1F N-glycan at EU position 297. In some embodiments, the first Fc domain comprises a G2F N-glycan at EU position 297 and the second Fc domain comprises a G2F N-glycan at EU position 297. In some embodiments, the first Fc domain comprises a G0F N-glycan at EU position 297 and the second Fc domain comprises a G0 N-glycan at EU position 297. In some embodiments, the first Fc domain comprises a G0 N-glycan at EU position 297 and the second Fc domain comprises a G0 N-glycan at EU position 297. In some embodiments, the first Fc domain comprises a G1F N-glycan at EU position 297 and the second Fc domain comprises a G2F+NANA N-glycan at EU position 297. In some embodiments, the first Fc domain comprises a G2F N-glycan at EU position 297 and the second Fc domain comprises a G2F+2×NANA N-glycan at EU position 297. 【0018】 In some embodiments, the amino acid sequences of the first and second Fc domains consist of SEQ ID NO:3 and SEQ ID NO:12, respectively. In some embodiments, the amino acid sequences of the first and second Fc domains consist of SEQ ID NO:3 and SEQ ID NO:9, respectively. In some embodiments, the amino acid sequences of the first and second Fc domains consist of SEQ ID NO:2 and SEQ ID NO:3, respectively. In some embodiments, the amino acid sequences of the first and second Fc domains consist of SEQ ID NO:3 and SEQ ID NO:6, respectively. 【0019】 In some embodiments, the amino acid sequence of the first Fc domain consists of any one of SEQ ID NOs: 2-22, and the amino acid sequence of the second Fc domain consists of any one of SEQ ID NOs: 2-22. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 2. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 3. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 4. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 5. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 6. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 7. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 8. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 9. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 10. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 11. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 12. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 13. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 14. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 15. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 16. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 17. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 18. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 19. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 20.In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 21. In some embodiments, the amino acid sequence of both the first and second Fc domains consists of SEQ ID NO: 22. 【0020】 In some embodiments, at least 85%, optionally 85% to 95%, of the Fc domains in the population lack an amino acid at EU position 441. In some embodiments, no more than 15%, optionally 5% to 15%, of the Fc domains in the population have glycine and lysine, respectively, at EU positions 440 and 441. In some embodiments, no more than 1% of the Fc domains in the population lack amino acids at EU positions 440 and 441 and comprise an amidated proline at EU position 439. 【0021】 In some embodiments, at least 95%, optionally 95%-99%, of the Fc domains in the population have aspartic acid, lysine, threonine, histidine, threonine, and cysteine ​​at EU positions 221, 222, 223, 224, 225, and 226, respectively. In some embodiments, 1% or less of the Fc domains in the population lack an amino acid at EU position 221 and have lysine, threonine, histidine, threonine, and cysteine ​​at EU positions 222, 223, 224, 225, and 226, respectively. In some embodiments, 1% or less of the Fc domains in the population lack an amino acid at EU positions 221 and 222 and have threonine, histidine, threonine, and cysteine ​​at EU positions 223, 224, 225, and 226, respectively. In some embodiments, no more than 2% of the Fc domains in the population lack amino acids at EU positions 221-224 and have a threonine and a cysteine, respectively, at EU positions 225 and 226. In some embodiments, no more than 1% of the Fc domains in the population lack amino acids at EU positions 221, 222, 223, 224, 225, and 226. 【0022】 In some embodiments, no more than 1% of the Fc domains in the population have aspartic acid isomerization at EU position 280 or 401. In some embodiments, no more than 10% of the Fc domains in the population have asparagine deamidation at EU position 384, 389, or 390. In some embodiments, no more than 3% of the Fc domains in the population have asparagine deamidation at EU position 315. In some embodiments, no more than 3% of the Fc domains in the population have asparagine deamidation at EU position 361. In some embodiments, no more than 1% of the Fc domains in the population have asparagine deamidation at EU position 276 or 286. In some embodiments, no more than 5% of the Fc domains have methionine oxidation at EU position 428. In some embodiments, no more than 1% of the Fc domains have proline amidation at EU position 445. In some embodiments, 1% or less of the Fc domains have an oxidation of tryptophan at EU position 277. 【0023】 In some embodiments, 0.5% or less of the FcRn antagonist molecules in the population are aggregated. In some embodiments, at least 95%, optionally at least 99%, of the dimers in the population are linked by at least one disulfide bond. In some embodiments, the average molecular weight of the non-aggregated FcRn antagonist molecules in the population is 54-56 kDa, optionally 54.4-54.7 kDa. In some embodiments, the percentage of free thiol groups in the population is 1% or less. 【0024】 In some embodiments, at least 35%, optionally 35%-55%, of the Fc domains in the population comprise galactose. In some embodiments, at least 90%, optionally 90%-98%, of the Fc domains in the population comprise fucose. In some embodiments, at most 1.5%, optionally 0.5%-1.5%, of the Fc domains in the population comprise sialic acid. 【0025】 In some embodiments, the composition described above or herein comprises an aqueous solution containing about 25 mM sodium phosphate, about 100 mM sodium chloride, and about 150 mM L-arginine, and about 0.02% (w / v) polysorbate 80, wherein the composition has a pH of about 6.7. In some embodiments, the composition comprises a 20 mg / ml population of FcRn antagonist molecules. 【0026】 In some embodiments, the composition described above or herein comprises an aqueous solution containing about 4 mM sodium phosphate, about 146 mM sodium chloride, and about 24 mM L-arginine, and about 0.0032% (w / v) polysorbate 80, wherein the composition has a pH of about 6.7. In some embodiments, the composition comprises about 3.2 mg / ml of a population of FcRn antagonist molecules. 【0027】 In some embodiments, the composition described above or herein comprises an aqueous solution comprising about 20 mM L-histidine, about 100 mM sodium chloride, about 60 mM sucrose, about 10 mM L-methionine, and about 0.04% (w / v) polysorbate 20, wherein the composition has a pH of about 6.0. In some embodiments, the composition comprises about 180 mg / ml of a population of FcRn antagonist molecules. 【0028】 In some embodiments, the composition described above or herein comprises an aqueous solution comprising about 20 mM L-histidine, about 50 mM L-arginine, about 100 mM sodium chloride, about 60 mM sucrose, about 10 mM L-methionine, and about 0.04% (w / v) polysorbate 80, wherein the composition has a pH of about 6.0. In some embodiments, the composition comprises about 200 mg / ml of a population of FcRn antagonist molecules. 【0029】 The present disclosure also provides an FcRn antagonist molecule comprising a variant Fc region comprising a homodimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first and second Fc domains consist of any one of SEQ ID NOs: 5 to 20 and 22. The present disclosure also provides a polynucleotide encoding the FcRn antagonist molecule. The present disclosure also provides a vector comprising the polynucleotide. The present disclosure also provides a cell comprising the polynucleotide. The present disclosure also provides a method of producing an FcRn antagonist molecule, the method comprising culturing the cells described above and herein under conditions such that the polynucleotides described above and herein are expressed and the FcRn antagonist molecule is produced. In some embodiments, the method also comprises isolating the FcRn antagonist molecule from the cells. 【0030】 The present disclosure also provides a method, comprising mixing the composition provided above and herein, the FcRn antagonist provided above and herein, the polynucleotide provided above and herein, the vector provided above and herein, or the cell provided above and herein with one or more pharmaceutically acceptable excipients. 【0031】 The present disclosure also provides a method of reducing serum IgG autoantibody levels in a subject, the method comprising administering to the subject any one or more of the compositions described above and provided herein, any one or more of the FcRn antagonists described above and provided herein, any one or more of the polynucleotides described above and provided herein, any one or more of the vectors described above and provided herein, or any one or more of the cells described above and provided herein. 【0032】 The present disclosure also provides a method of treating an autoimmune disease in a subject, the method comprising administering to the subject any one or more of the compositions described above and provided herein, any one or more of the FcRn antagonists described above and provided herein, any one or more of the polynucleotides described above and provided herein, any one or more of the vectors described above and provided herein, or any one or more of the cells described above and provided herein. 【0033】 The present disclosure also provides any one or more of the compositions described above and provided herein, any one or more of the FcRn antagonists described above and provided herein, any one or more of the polynucleotides described above and provided herein, any one or more of the vectors described above and provided herein, or any one or more of the cells described above and provided herein for use in treating an autoimmune disease. 【0034】 The present disclosure also provides use of any one or more of the compositions described above and provided herein, any one or more of the FcRn antagonists described above and provided herein, any one or more of the polynucleotides described above and provided herein, any one or more of the vectors described above and provided herein, or any one or more of the cells described above and provided herein for the treatment of an autoimmune disease. 【0035】 The present disclosure also provides any one or more of the compositions described above and provided herein, any one or more of the FcRn antagonists described above and provided herein, any one or more of the polynucleotides described above and provided herein, any one or more of the vectors described above and provided herein, or any one or more of the cells described above and provided herein for use in the manufacture of a medicament for the treatment of an autoimmune disease. 【0036】 The present disclosure also provides any one or more of the compositions described above and provided herein, any one or more of the FcRn antagonists described above and provided herein, any one or more of the polynucleotides described above and provided herein, any one or more of the vectors described above and provided herein, or any one or more of the cells described above and provided herein for use in medicine. [Brief explanation of the drawings] 【0037】 [Figure 1] Figure 1 shows chromatograms of cation exchange high performance liquid chromatography (CEX HPLC) fractionation of FcRn antagonist reference standard batch 2 and batch 3. In each case, absorbance at 220 nm (AU) is plotted against relative column retention time. 【0038】 [Figure 2] Chromatograms of CEX HPLC fractionation of FcRn antagonists for a population of FcRn antagonist molecules produced from the ARFCB11 cell line are shown. In each case, absorbance at 220 nm (AU) is plotted against relative column retention time. 【0039】 [Figure 3] Chromatograms of imaging capillary isoelectric focusing (icIEF) results for reference standard batch 2 and batch 3 are shown. 【0040】 [Figure 4] 1 shows a line graph depicting % area under the curve for charge variant 4 over storage time in months at -70°C, +5°C, and +25°C. 【0041】 [Figure 5] 1 shows a line graph depicting the % area under the curve for charge variant 5 over storage time in months at -70°C, +5°C, and +25°C. 【0042】 [Figure 6] 1 shows a line graph depicting the % area under the curve for charge variant 9 over storage time in months at -70°C, +5°C, and +25°C. 【0043】 [Figure 7] 1 shows a line graph depicting the % area under the curve for charge variant 11 over storage time in months at -70°C, +5°C, and +25°C. 【0044】 [Figure 8] 1 shows a line graph depicting the % area under the curve for charged isoform 1 over storage time in months at -70°C, +5°C, and +25°C. 【0045】 [Figure 9] 1 shows a line graph depicting % area under the curve for charged isoform 2 over storage time in months at -70°C, +5°C, and +25°C. 【0046】 [Figure 10] Figure 1 shows a hydrophilic interaction liquid chromatography (HILIC) chromatogram of a 2-aminobenzamide (2-AB) labeled reference sample. 【0047】 [Figure 11] 11 shows an enlarged version of a portion of FIG. 【0048】 [Figure 12] 1 shows a bar graph depicting the relative percent intensities of 2-AB labeled glycans in a reference sample. 【0049】 [Figure 13] 1 shows a bar graph depicting the relative percent intensities of galactosylation, fucosylation, and sialylation in reference samples. 【0050】 [Figure 14]1 shows a set of reversed-phase liquid chromatography-UV detection (RPLC-UV) 214 nm spectral absorbance plots showing electrospray ionization mass spectrometry (ESI-MS) results for reference standard batch 1, batch 2, and batch 3. 【0051】 [Figure 15] Deconvoluted spectra of the major peaks observed in the RPLC-UV 214 nm profile of the reference sample with glycoform annotation for samples batch 1, batch 2, and batch 3 are shown. 【0052】 [Figure 16] 1 shows a bar graph showing a graphical representation of N-glycosylation for samples batch 1, batch 2, and batch 3. 【0053】 [Figure 17] 1 shows gel permeation high performance liquid chromatography (GP-HPLC) profiles for reference standards batch 2 and batch 3. 【0054】 [Figure 18] 1 shows non-reducing capillary electrophoresis sodium dodecyl sulfate (CE-SDS) profiles for reference standards batch 2 and batch 3. DETAILED DESCRIPTION OF THE INVENTION 【0055】 The present disclosure provides FcRn antagonist molecules and compositions comprising these FcRn antagonist molecules. The FcRn antagonist molecules and compositions provided herein are capable of reducing serum levels of IgG antibodies (e.g., IgG autoantibodies) in a subject. Also provided herein are nucleic acids encoding the FcRn antagonist molecules, as well as vectors, host cells, production methods, and methods of using them in the treatment of IgG antibody-mediated disorders. 【0056】 definition As used herein, the term "FcRn" refers to neonatal Fc receptor. Exemplary FcRn molecules include human FcRn, encoded by the FCGRT gene as shown in RefSeq NM 004107. The amino acid sequence of the corresponding protein is shown in RefSeq NP_004098. 【0057】 As used herein, the term "FcRn antagonist molecule" refers to any agent that specifically binds to FcRn and inhibits the binding of an immunoglobulin to FcRn (e.g., human FcRn). In one embodiment, the FcRn antagonist comprises an Fc region (e.g., a variant Fc region disclosed herein), which specifically binds to FcRn and inhibits the binding of IgG to FcRn. In one embodiment, the FcRn antagonist is not a full-length IgG antibody. In one embodiment, the FcRn antagonist comprises an antigen-binding domain that binds to a target antigen and a variant Fc region. In one embodiment, the term "FcRn antagonist molecule" refers to an antibody or antigen-binding fragment thereof that specifically binds to FcRn via its antigen-binding domain and / or its Fc region and inhibits the binding of the Fc region of an immunoglobulin (e.g., an IgG autoantibody) to FcRn. 【0058】 As used herein, the term "affinity" or "binding affinity" refers to the strength of the binding interaction between two molecules. 【0059】 As used herein, the term "specifically binds" refers to the ability of any molecule to preferentially bind to a given target. For example, a molecule that specifically binds to a given target can bind other molecules, generally with lower affinity, as determined, for example, by immunoassay, BIAcore™, KinExA 3000 instrument (Sapidyne Instruments, Boise, Id.), or other assays known in the art. In specific embodiments, a molecule that specifically binds to a given target binds to the antigen with a KD that is at least 2, 2.5, 3, or 4 logs lower than the KD when the molecule nonspecifically binds to another target. 【0060】 As used herein, the term "operably linked" refers to the linkage of polynucleotide sequence elements in a functional relationship. For example, a polynucleotide sequence is operably linked when it is placed into a functional relationship with another polynucleotide sequence. In some embodiments, a transcriptional regulatory polynucleotide sequence, e.g., a promoter, enhancer, or other expression control element, is operably linked to a protein-encoding polynucleotide sequence if it affects the transcription of the protein-encoding polynucleotide sequence. Operably linked elements can be contiguous or non-contiguous. 【0061】 As used herein, the term "linked" refers to a physical connection (e.g., directly or indirectly connected) between amino acid sequences (e.g., different segments, regions, or domains). Linked regions, domains, and segments of the FcRn antagonist molecules of the present disclosure can be contiguous or non-contiguous (e.g., connected to each other via a linker). In some embodiments, the connection is a covalent bond. In some embodiments, the connection is a non-covalent bond. 【0062】 As used herein, the term "covalently linked" refers to the linking of two molecules or chemical moieties by a covalent bond. In some embodiments, the covalent bond is a peptide bond or a disulfide bond. As used herein, the term "fused" refers to the linking of two peptides by a peptide bond or a peptide linker. In some embodiments, two proteins are fused together directly and contiguously by a peptide bond. In some embodiments, two proteins are fused indirectly and non-contiguously via a peptide linker. In some embodiments, one protein is fused at a first position to a peptide linker by a peptide bond, and a second protein is fused at a second position to a peptide linker by a peptide bond. As used herein, the term "non-covalently linked" refers to the linking of two molecules or chemical moieties by a non-covalent interaction or non-covalent bond. In some embodiments, non-covalent interactions or non-covalent bonds include hydrogen bonds, electrostatic bonds or interactions, halogen bonds, pi-stacking, and van der Waals interactions. 【0063】 As used herein, the terms "antibody" and "antibodies" include full-length antibodies, antigen-binding fragments of full-length antibodies, and molecules comprising an antibody CDR, VH region, or VL region. Examples of antibodies include monoclonal antibodies, recombinantly produced antibodies, monospecific antibodies, multispecific antibodies (including bispecific antibodies), human antibodies, humanized antibodies, chimeric antibodies, immunoglobulins, synthetic antibodies, tetrameric antibodies comprising two heavy chain and two light chain molecules, antibody light chain monomers, antibody heavy chain monomers, antibody light chain dimers, antibody heavy chain dimers, antibody light chain-antibody heavy chain pairs, intrabodies, heteroconjugate antibodies, antibody-drug conjugates, single domain antibodies (sdAbs), monovalent antibodies, single chain antibodies or single chain Fvs (scFvs), camelid antibodies, single domain antibodies (sdAbs), humanized antibodies, affibody molecules, VHH fragments, Fab fragments, F(ab')2 fragments, disulfide-linked Fvs (sdFvs), anti-idiotypic (anti-Id) antibodies (including, for example, anti-anti-Id antibodies), and antigen-binding fragments of any of the above. The antibody can be of any isotype (e.g., IgG, IgE, IgM, IgD, IgA, or IgY), any subclass (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, or IgA2), or species (e.g., murine IgG2a or IgG2b) of immunoglobulin molecule. 【0064】 As used herein, the term "Fc region" refers to the portion of an immunoglobulin formed by the Fc domains of its two heavy chains. The Fc region may be a wild-type Fc region (native Fc region) or a variant Fc region. A native Fc region is a homodimer. The Fc region may be derived from any naturally occurring immunoglobulin. In some embodiments, the Fc region is formed from an IgA, IgD, IgE, or IgG heavy chain constant region. In some embodiments, the Fc region is formed from an IgG heavy chain constant region. In some embodiments, the IgG heavy chain is an IgG1, IgG2, IgG3, or IgG4 heavy chain constant region. In some embodiments, the Fc region is formed from an IgG1 heavy chain constant region. In some embodiments, the IgG1 heavy chain constant region comprises the G1m1(a), G1m2(x), G1m3(f), or G1m17(z) allotype. See, e.g., Jefferis and Lefranc, (2009) mAbs 1(4):332-338, and de Taeye et al., (2020) Front Immunol. 11:740, which are incorporated by reference in their entireties. 【0065】 As used herein, the term "variant Fc region" refers to a variant of an Fc region having one or more changes relative to a native Fc region. Modifications can include amino acid substitutions, additions and / or deletions, attachment of additional moieties, and / or modifications of native glycans. The term encompasses heterodimeric Fc regions in which each of the constituent Fc domains is different. The term also encompasses single-chain Fc regions in which the constituent Fc domains are linked together by linker moieties. 【0066】 As used herein, the term "Fc domain" refers to the portion of a single immunoglobulin heavy chain that comprises both the CH2 and CH3 domains of an antibody. In some embodiments, the Fc domain comprises at least a portion of the hinge (e.g., upper, middle, and / or lower hinge region), the CH2 domain, and the CH3 domain. In some embodiments, the Fc domain does not comprise the hinge region. 【0067】 As used herein, the term "hinge region" refers to the portion of a heavy chain molecule that connects the CH1 domain to the CH2 domain. In some embodiments, the hinge region is at most 70 amino acid residues in length. In some embodiments, this hinge region comprises approximately 11 to 17 amino acid residues and is flexible, thus allowing the two N-terminal antigen-binding regions to move independently. In some embodiments, the hinge region is 12 amino acids in length. In some embodiments, the hinge region is 15 amino acids in length. In some embodiments, the hinge region is 62 amino acids in length. The hinge region can be subdivided into three distinct domains: the upper, middle, and lower hinge domains. The FcRn antagonist molecules of the present disclosure can comprise all or any portion of the hinge region. In some embodiments, the hinge region is derived from an IgG1 antibody. In some embodiments, the hinge region comprises the amino acid sequence EPKSCDKTHTCPPCP (SEQ ID NO: 23). 【0068】 As used herein, the term "EU position" refers to an amino acid position in the EU numbering system for the Fc region as described in Edelman, GM et al., Proc. Natl. Acad. USA, 63, 78-85 (1969), and Kabat et al., "Sequences of Proteins of Immunological Interest," USDept. Health and Human Services, 5th edition, 1991. 【0069】 As used herein, the term "antibody-mediated disorder" refers to any disorder in which the symptoms of the disorder are caused by abnormal levels of one or more antibodies in a subject. As used herein, the term "autoantibody-mediated disorder" refers to any disease or disorder in which the underlying pathology is caused, at least in part, by pathogenic IgG autoantibodies. 【0070】 As used herein, the terms "treat," "treating," and "treatment" refer to therapeutic or prophylactic measures as described herein. Methods of "treatment" employ administering a polypeptide to a subject having or susceptible to a disease or disorder to prevent, cure, delay, reduce the severity of, or ameliorate a disease or disorder, or one or more symptoms of a recurrent disease or disorder, or to prolong the subject's survival beyond that expected in the absence of such treatment. 【0071】 As used herein, in the context of administering therapy, the term "effective amount" refers to the amount of therapy that achieves the desired prophylactic or therapeutic effect. 【0072】 As used herein, the term "dose" or "dosage" refers to the amount of a drug administered to a subject in a single administration. 【0073】 As used herein, the term "subject," or "patient," or "participant" includes any human or non-human animal. In one embodiment, the subject, or patient, or participant is a human or non-human mammal. In one embodiment, the subject, or patient, or participant is a human. 【0074】 As used herein, the terms "about" or "approximately," when referring to measurable values, eg, dosages, encompass a ±5% variation of a given value or range. 【0075】 As used herein, the term "molecular weight" can refer to a "predicted molecular weight" or an "observed molecular weight." The "predicted molecular weight" of a protein is the sum of the molecular weights of all amino acids in the protein. In certain circumstances, the "predicted molecular weight" can differ from the "observed molecular weight" of a molecule. In some embodiments, these differences can occur in a protein due to alterations in glycosylation, glycanation, ubiquitination, phosphorylation, or proteolytic cleavage of the protein or complexes of additional proteins with a given protein. 【0076】 FcRn antagonist molecules The FcRn antagonist molecules disclosed herein comprise or consist of at least one Fc domain comprising or consisting of the amino acid sequence of SEQ ID NO: 1, as provided below. Table 1 [Table 1] 【0077】 In some embodiments, the FcRn antagonist molecules disclosed herein comprise or consist of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO:1. 【0078】 The present disclosure also provides a population of FcRn antagonist molecules, wherein the FcRn antagonist molecules in the population comprise or consist of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequence of SEQ ID NO: 1, with the proviso that the population is not a homogeneous population of homodimeric FcRn antagonist molecules in which the amino acid sequences of both the first and second Fc domains comprise or consist of the amino acid sequence of SEQ ID NO: 2, 3, 20, or 21 listed in Table 2. Table 2 [Table 2] 【0079】 In some embodiments, each FcRn antagonist molecule in the population comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 2 to 22, provided that the population is not a homogeneous population of homodimeric FcRn antagonist molecules in which the amino acid sequences of both the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 2, 3, 20, or 21 listed in Table 2. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 2 to 22, provided that the population is not a homogeneous population of homodimeric FcRn antagonist molecules in which the amino acid sequences of both the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 2, 3, 20, or 21. The amino acid sequences of SEQ ID NOs: 4 to 19 and 22 listed in Table 3. Table 3 [Table 3] TIFF2025537777000004.tif132170 【0080】 Various embodiments of FcRn antagonist molecules are shown below in Table 4. The amino acid sequence of each member of the dimer of the first Fc domain (I) and the second Fc domain (II) is represented by a SEQ ID NO. Thus, for example, I=2 and II=3 shown in the second cell of Table 4 represent FcRn antagonist molecules in the population that comprise or consist of a variant Fc region comprising or consisting of a dimer of the first Fc domain (I) and the second Fc domain (II), and the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 2 and 3, respectively. Table 4 [Table 4] 【0081】 In some embodiments, the populations of FcRn antagonist molecules described herein are not homogeneous populations of homodimeric FcRn antagonist molecules in which the amino acid sequences of both the first and second Fc domains consist of the amino acid sequences of SEQ ID NO: 2, 3, 20, or 21. In some embodiments, the populations of FcRn antagonist molecules described herein include homodimeric FcRn antagonist molecules in which the amino acid sequences of both the first and second Fc domains consist of the amino acid sequences of SEQ ID NO: 2, 3, 20, or 21, but these populations further include other FcRn antagonist molecules. In some embodiments, these other FcRn antagonist molecules are listed in Table 4 above, i.e., except when I=2 and II=2, I=3 and II=3, I=20 and II=20, and I=21 and II=21. 【0082】 In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NOs: 3 and 12, respectively. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequence of SEQ ID NOs: 3 and 12, respectively. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequences of SEQ ID NOs: 3 and 9, respectively. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 3 and 9, respectively. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequences of SEQ ID NOs: 2 and 3, respectively.In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 2 and 3, respectively. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NOs: 3 and 6, respectively. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 3 and 6, respectively. 【0083】 In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:4. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:5. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:6. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:7.In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 8. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 9. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 10. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:11.In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 12. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 13. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 14. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 15.In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 16. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 17. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 18. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 19.In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:22. 【0084】 In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 4. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 5. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 6. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 7. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 8. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 9.In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 10. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 11. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 12. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 13. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 14. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 15.In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 16. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 17. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 18. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 19. In some embodiments, each FcRn antagonist molecule in the population comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 22. 【0085】 In some embodiments, the FcRn antagonist molecules in the population comprise glycanation in one or both of their Fc domains. In some embodiments, the FcRn antagonist molecules in the population comprise glycanation at EU position 297 in one or both of their Fc domains. In some embodiments, the glycanation comprises an N-glycan. In some embodiments, the N-glycan comprises a G0F N-glycan, a G1F N-glycan, a G2F N-glycan, or a G0 N-glycan. 【0086】 In some embodiments, the FcRn antagonist molecule comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, one of the Fc domains being glycanated. In some embodiments, the glycanation comprises an N-glycan. In some embodiments, the N-glycan comprises a G0F N-glycan, a G1F N-glycan, a G2F N-glycan, or a G0 N-glycan. 【0087】 In some embodiments, the FcRn antagonist molecule comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, both of which Fc domains are glycanated. In some embodiments, the glycanation comprises N-glycans. In some embodiments, the N-glycans comprise G0F N-glycans, G1F N-glycans, G2F N-glycans, or G0 N-glycans. In some embodiments, the Fc domain comprises G0F N-glycans. In some embodiments, the Fc domain comprises G1F N-glycans. In some embodiments, the Fc domain comprises G2F N-glycans. In some embodiments, the Fc domain comprises G0 N-glycans. 【0088】 In some embodiments, the first Fc domain and the second Fc domain have different N-glycanation at EU position 297. In some embodiments, the first Fc domain comprises a G0F N-glycan and the second Fc domain comprises a G1F N-glycan. In some embodiments, the first Fc domain comprises a G0F N-glycan and the second Fc domain comprises a G2F N-glycan. In some embodiments, the first Fc domain comprises a G0F N-glycan and the second Fc domain comprises a G0 N-glycan. In some embodiments, the first Fc domain comprises a G1F N-glycan and the second Fc domain comprises a G2F N-glycan. In some embodiments, the first Fc domain comprises a G1F N-glycan and the second Fc domain comprises a G2F+NANA N-glycan. In some embodiments, the first Fc domain comprises a G2F N-glycan and the second Fc domain comprises a G2F+2×NANA N-glycan. In some embodiments, the first Fc domain comprises a G1F N-glycan and the second Fc domain comprises a G0 N-glycan. In some embodiments, the first Fc domain comprises a G2F N-glycan and the second Fc domain comprises a G0 N-glycan. In some embodiments, one or more of the amino acids of the FcRn antagonist molecule are modified. In some embodiments, an asparagine residue is deaminated. In some embodiments, a methionine residue is oxidized. In some embodiments, a tryptophan residue is oxidized. In some embodiments, both the methionine and tryptophan residues are oxidized. 【0089】 In some embodiments, the population of FcRn antagonist molecules comprises or consists of multiple subpopulations of FcRn antagonist molecules. In some embodiments, the population of FcRn antagonist molecules comprises or consists of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 subpopulations. 【0090】 In some embodiments, a first subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:3. 【0091】 In some embodiments, a second subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs: 3 and 12, respectively. 【0092】 In some embodiments, a third subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs: 3 and 9, respectively. 【0093】 In some embodiments, a fourth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 3, and wherein two asparagine residues in each FcRn antagonist molecule in the fourth subpopulation are deamidated. 【0094】 In some embodiments, a fifth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs: 3 and 9, respectively, and one asparagine residue in each FcRn antagonist molecule in the fifth subpopulation is deamidated. 【0095】 In some embodiments, a sixth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs: 2 and 3, respectively. 【0096】 In some embodiments, a seventh subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs: 2 and 3, respectively, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the seventh subpopulation is oxidized. 【0097】 In some embodiments, an eighth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:2. 【0098】 In some embodiments, a ninth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs: 3 and 6, respectively. 【0099】 In some embodiments, a tenth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequences of SEQ ID NOs: 2 and 3, respectively, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the tenth subpopulation is oxidized. 【0100】 In some embodiments, an eleventh subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of both the first and second Fc domains comprise or consist of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 3, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the eleventh subpopulation is oxidized. 【0101】 In some embodiments, a first subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO:3. 【0102】 In some embodiments, a second subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 3 and 12, respectively. 【0103】 In some embodiments, a third subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 3 and 9, respectively. 【0104】 In some embodiments, a fourth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 3, and wherein two asparagine residues in each FcRn antagonist molecule in the fourth subpopulation are deamidated. 【0105】 In some embodiments, a fifth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 3 and 9, respectively, and one asparagine residue in each FcRn antagonist molecule in the fifth subpopulation is deamidated. 【0106】 In some embodiments, a sixth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 2 and 3, respectively. 【0107】 In some embodiments, a seventh subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 2 and 3, respectively, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the seventh subpopulation is oxidized. 【0108】 In some embodiments, an eighth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO:2. 【0109】 In some embodiments, a ninth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 3 and 6, respectively. 【0110】 In some embodiments, a tenth subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequences of the first and second Fc domains comprise or consist of the amino acid sequences of SEQ ID NOs: 2 and 3, respectively, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the tenth subpopulation is oxidized. 【0111】 In some embodiments, an eleventh subpopulation of FcRn antagonist molecules comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, wherein the amino acid sequence of both the first and second Fc domains comprises or consists of the amino acid sequence of SEQ ID NO: 3, and one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the eleventh subpopulation is oxidized. 【0112】 In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with one of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with two of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with three of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with four of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with five of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with six of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with seven of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with eight of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with nine of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations.In some embodiments, the population of FcRn antagonist molecules comprises or consists of the first subpopulation combined with all of the second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, or eleventh subpopulations. 【0113】 In some embodiments, the population comprises or consists of the first and second subpopulations. In some embodiments, the population comprises or consists of the first and third subpopulations. In some embodiments, the population comprises or consists of the first and fourth subpopulations. In some embodiments, the population comprises or consists of the first and fifth subpopulations. In some embodiments, the population comprises or consists of the first and sixth subpopulations. In some embodiments, the population comprises or consists of the first and seventh subpopulations. In some embodiments, the population comprises or consists of the first and eighth subpopulations. In some embodiments, the population comprises or consists of the first and ninth subpopulations. In some embodiments, the population comprises or consists of the first and tenth subpopulations. In some embodiments, the population comprises or consists of the first and eleventh subpopulations. In some embodiments, the populations listed above further comprise or consist of 1, 2, 3, 4, 5, 6, 7, 8, or 9 additional subpopulations. In some embodiments, these additional subpopulations are one or more of those described above. 【0114】 In some embodiments, the population comprises or consists of subpopulations 1, and 7, 9, or 11. In some embodiments, the population comprises or consists of subpopulations 1, 7, 9, and 11. 【0115】 In some embodiments, the first subpopulation constitutes at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, or at least 90% of the population of FcRn antagonist molecules. In some embodiments, the first subpopulation constitutes about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, or about 90% of the population of FcRn antagonist molecules. In some embodiments, the first subpopulation constitutes 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% of the population of FcRn antagonist molecules. In some embodiments, the first subpopulation comprises 40% to 90%, 50% to 80%, or 55% to 70% of the population of FcRn antagonist molecules, or 56.9% to 68.3%, or 59.5% to 67.9% of the population of FcRn antagonist molecules. 【0116】 In some embodiments, the second subpopulation comprises less than 3.0%, less than 2.5%, less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the second subpopulation comprises about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the second subpopulation comprises 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the second subpopulation comprises 0.5% to 3.0%, 1.0% to 2.5%, or 1.0% to 2.0% of the population of FcRn antagonist molecules. In some embodiments, the second subpopulation comprises 0.8% to 2.0% or 0.8% to 2.1% of the population of FcRn antagonist molecules. 【0117】 In some embodiments, the third subpopulation constitutes less than 3.0%, less than 2.5%, less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the third subpopulation constitutes about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the third subpopulation constitutes 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the third subpopulation constitutes 0.5% to 3.0%, 1.0% to 2.5%, or 1.0% to 2.0% of the population of FcRn antagonist molecules. In some embodiments, the third subpopulation comprises 1.1% to 2.1% or 1.0% to 1.9% of the population of FcRn antagonist molecules. 【0118】 In some embodiments, the fourth subpopulation constitutes less than 5%, less than 4%, less than 3%, less than 2%, or less than 1% of the population of FcRn antagonist molecules. In some embodiments, the fourth subpopulation constitutes about 5%, about 4%, about 3%, about 2%, or about 1% of the population of FcRn antagonist molecules. In some embodiments, the fourth subpopulation constitutes 5%, 4%, 3%, 2%, or 1% of the population of FcRn antagonist molecules. In some embodiments, the fourth subpopulation constitutes 1% to 5%, 2% to 4%, or 2% to 3% of the population of FcRn antagonist molecules. In some embodiments, the fourth subpopulation constitutes 2.1% to 3.2%, or 2.0% to 3.1% of the population of FcRn antagonist molecules. 【0119】 In some embodiments, the fifth subpopulation constitutes less than 12%, less than 11%, less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, or less than 5% of the population of FcRn antagonist molecules. In some embodiments, the fifth subpopulation constitutes about 12%, about 11%, about 10%, about 9%, about 8%, about 7%, about 6%, or about 5% of the population of FcRn antagonist molecules. In some embodiments, the fifth subpopulation constitutes 12%, 11%, 10%, 9%, 8%, 7%, 6%, or 5% of the population of FcRn antagonist molecules. In some embodiments, the fifth subpopulation constitutes 5% to 12%, 6% to 10%, or 7% to 8% of the population of FcRn antagonist molecules. In some embodiments, the fifth subpopulation comprises 6.8% to 9.4% or 6.9% to 8.7% of the population of FcRn antagonist molecules. 【0120】 In some embodiments, the sixth subpopulation constitutes less than 17%, less than 16%, less than 15%, less than 14%, less than 13%, less than 12%, less than 11%, less than 10%, less than 9%, less than 8%, less than 7%, or less than 6% of the population of FcRn antagonist molecules. In some embodiments, the sixth subpopulation constitutes about 17%, about 16%, about 15%, about 14%, about 13%, about 12%, about 11%, about 10%, about 9%, about 8%, about 7%, or about 6% of the population of FcRn antagonist molecules. In some embodiments, the sixth subpopulation constitutes 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, or 6% of the population of FcRn antagonist molecules. In some embodiments, the sixth subpopulation comprises 7% to 17%, 10% to 15%, or 11% to 12% of the population of FcRn antagonist molecules, hi some embodiments, the sixth subpopulation comprises 7.0% to 14.0%, or 10.0% to 14.4% of the population of FcRn antagonist molecules. 【0121】 In some embodiments, the seventh subpopulation comprises less than 6.0%, less than 5.5%, less than 5.0%, less than 4.5%, less than 4.0%, less than 3.5%, less than 3.0%, less than 2.5%, less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules, hi some embodiments, the seventh subpopulation comprises about 6.0%, about 5.5%, about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the seventh subpopulation comprises 6.0%, 5.5%, 5.0%, 4.5%, 4.0%, 3.5%, 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the seventh subpopulation comprises 0.5% to 5.5%, 1.0% to 3.0%, or 1.5% to 2.5% of the population of FcRn antagonist molecules. In some embodiments, the seventh subpopulation comprises 1.5% to 5.5%, or 1.4% to 4.9% of the population of FcRn antagonist molecules. 【0122】 In some embodiments, the eighth subpopulation comprises less than 7.5%, less than 7.0%, less than 6.5%, less than 6.0%, less than 5.5%, less than 5.0%, less than 4.5%, less than 4.0%, less than 3.5%, less than 3.0%, or less than 2.5% of the population of FcRn antagonist molecules, hi some embodiments, the eighth subpopulation comprises about 7.5%, about 7.0%, about 6.5%, about 6.0%, about 5.5%, about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, or about 2.5% of the population of FcRn antagonist molecules. In some embodiments, the eighth subpopulation comprises 7.5%, 7.0%, 6.5%, 6.0%, 5.5%, 5.0%, 4.5%, 4.0%, 3.5%, 3.0%, or 2.5% of the population of FcRn antagonist molecules. In some embodiments, the eighth subpopulation comprises 2.5% to 7.5%, 3.0% to 5.0%, or 3.5% to 4.5% of the population of FcRn antagonist molecules. In some embodiments, the eighth subpopulation comprises 2.9% to 7.4%, or 3.0% to 6.3% of the population of FcRn antagonist molecules. 【0123】 In some embodiments, the ninth subpopulation constitutes less than 3.5%, less than 3.0%, less than 2.5%, less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the ninth subpopulation constitutes about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the ninth subpopulation constitutes 3.5%, 3.0%, 2.5%, 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the ninth subpopulation constitutes 0.5% to 3.5%, 1.5% to 2.0%, or 1.0% to 1.5% of the population of FcRn antagonist molecules. In some embodiments, the ninth subpopulation comprises 0.4% to 3.2% or 0.5% to 2.6% of the population of FcRn antagonist molecules. 【0124】 In some embodiments, the tenth subpopulation comprises less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the tenth subpopulation comprises about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the tenth subpopulation comprises 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the tenth subpopulation comprises 0.5% to 2.0%, 0.5% to 1.5%, or 1.0% to 1.5% of the population of FcRn antagonist molecules. 【0125】 In some embodiments, the 11th subpopulation constitutes less than 2.0%, less than 1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the 11th subpopulation constitutes about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the 11th subpopulation constitutes 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the 11th subpopulation constitutes 0.5% to 2.0%, 0.5% to 1.5%, or 1.0% to 1.5% of the population of FcRn antagonist molecules. 【0126】 In some embodiments, the FcRn antagonist molecules in the population comprise glycanation in one or both of their Fc domains. In some embodiments, the FcRn antagonist molecules in the population comprise glycanation at EU position 297 in one or both of their Fc domains. In some embodiments, the glycanation comprises an N-glycan. In some embodiments, the N-glycan comprises a G0F N-glycan, a G1F N-glycan, a G2F N-glycan, or a G0 N-glycan. 【0127】 In some embodiments, the FcRn antagonist molecule comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, one of the Fc domains being glycanated. In some embodiments, the glycanation comprises an N-glycan. In some embodiments, the N-glycan comprises a G0F N-glycan, a G1F N-glycan, a G2F N-glycan, or a G0 N-glycan. 【0128】 In some embodiments, the FcRn antagonist molecule comprises or consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, both of which Fc domains are glycanated. In some embodiments, the glycanation comprises N-glycans. In some embodiments, the N-glycans comprise G0F N-glycans, G1F N-glycans, G2F N-glycans, or G0 N-glycans. In some embodiments, the Fc domain comprises G0F N-glycans. In some embodiments, the Fc domain comprises G1F N-glycans. In some embodiments, the Fc domain comprises G2F N-glycans. In some embodiments, the Fc domain comprises G0 N-glycans. 【0129】 In some embodiments, the first Fc domain and the second Fc domain have different N-glycanation at EU position 297. In some embodiments, the first Fc domain comprises a G0F N-glycan and the second Fc domain comprises a G1F N-glycan. In some embodiments, the first Fc domain comprises a G0F N-glycan and the second Fc domain comprises a G2F N-glycan. In some embodiments, the first Fc domain comprises a G0F N-glycan and the second Fc domain comprises a G0 N-glycan. In some embodiments, the first Fc domain comprises a G1F N-glycan and the second Fc domain comprises a G2F N-glycan. In some embodiments, the first Fc domain comprises a G1F N-glycan and the second Fc domain comprises a G2F+NANA N-glycan. In some embodiments, the first Fc domain comprises a G2F N-glycan and the second Fc domain comprises a G2F+2×NANA N-glycan. In some embodiments, the first Fc domain comprises a G1F N-glycan and the second Fc domain comprises a G0 N-glycan. In some embodiments, the first Fc domain comprises a G2F N-glycan and the second Fc domain comprises a G0 N-glycan. 【0130】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the population of Fc domains of the FcRn antagonist molecules comprise an N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 95%, about 96%, about 97%, about 98%, or about 99% of the population of Fc domains of the FcRn antagonist molecules comprise an N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 95%, 96%, 97%, 98%, or 99% of the population of Fc domains of the FcRn antagonist molecules comprise an N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 95% to 99%, 96% to 99%, or 97% to 99%% of the population of Fc domains of the FcRn antagonist molecules comprise an N-glycan at EU position 297. 【0131】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 48%, at least 49%, at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, or at least 67% of the population of Fc domains of the FcRn antagonist molecules comprise a GOF N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, or about 67% of the population of Fc domains of the FcRn antagonist molecules comprise a GOF N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, or 67% of the population of FcRn antagonist molecule Fc domains comprise a GOF N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 48% to 67%, 51% to 66%, or 50% to 65% of the population of Fc domains of FcRn antagonist molecules comprise a GOF N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 53.8% to 64.1% or 53.8% to 63.1% of the population of Fc domains of the FcRn antagonist molecules comprise a GOF N-glycan at EU position 297. 【0132】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 21%, at least 22%, at least 23%, at least 24%, at least 25%, at least 26%, at least 27%, at least 28%, at least 29%, at least 30%, at least 31%, or at least 32% of the population of Fc domains of the FcRn antagonist molecules comprise a G1F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, or about 30%, about 31%, or about 32% of the population of Fc domains of the FcRn antagonist molecules comprise a G1F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, or 32% of the population of Fc domains of the FcRn antagonist molecules comprise the G1F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 21% to 32%, 24% to 31%, or 25% to 30% of the population of Fc domains of the FcRn antagonist molecules comprise the G1F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 22.6% to 28.3% or 23.5% to 28.0% of the population of Fc domains of the FcRn antagonist molecules comprise a G1F N-glycan at EU position 297. 【0133】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, or at least 12% of the population of Fc domains of the FcRn antagonist molecules comprise a G2F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, or about 12% of the population of Fc domains of the FcRn antagonist molecules comprise a G2F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, or 12% of the population of Fc domains of the FcRn antagonist molecules comprise a G2F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 3% to 12%, 5% to 11%, or 7% to 10% of the population of Fc domains of the FcRn antagonist molecules comprise a G2F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 5.6% to 9.2% or 6.2% to 9.2% of the population of Fc domains of the FcRn antagonist molecules comprise a G2F N-glycan at EU position 297. 【0134】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, or at least 6% of the population of Fc domains of the FcRn antagonist molecules comprise a G0 N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 1%, about 2%, about 3%, about 4%, about 5%, or about 6% of the population of Fc domains of the FcRn antagonist molecules comprise a G0 N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 1%, 2%, 3%, 4%, 5%, or 6% of the population of Fc domains of the FcRn antagonist molecules comprise a G0 N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 1% to 6%, 2% to 5%, or 2% to 4% of the population of Fc domains of the FcRn antagonist molecules comprise a G0 N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 2.5% to 4.5%, or 2.5% to 3.2% of the population of Fc domains of the FcRn antagonist molecules comprise a G0 N-glycan at EU position 297. 【0135】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 33%, at least 34%, at least 35%, at least 36%, at least 37%, at least 38%, at least 39%, at least 40%, at least 41%, at least 42%, at least 43%, at least 44%, at least 45%, at least 46%, at least 47%, at least 48%, at least 49%, at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, or at least 57% of the population of Fc domains of the FcRn antagonist molecules comprise galactose. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, or about 57% of the population of FcRn antagonist molecule Fc domains comprise galactose. In some embodiments, the population comprises or consists of FcRn antagonist molecules, and 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, or 57% of the population of FcRn antagonist molecule Fc domains comprise galactose. In some embodiments, the population comprises or consists of FcRn antagonist molecules, and 33% to 57%, 34% to 56%, or 35% to 55% of the population of FcRn antagonist molecule Fc domains comprise galactose. 【0136】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the population of FcRn antagonist molecule Fc domains comprise fucose. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% of the population of FcRn antagonist molecule Fc domains comprise fucose. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the population of FcRn antagonist molecule Fc domains comprise fucose. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 33% to 57%, 34% to 56%, or 35% to 55% of the population of FcRn antagonist molecule Fc domains comprise fucose. 【0137】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at most 0.3%, at most 0.4%, at most 0.5%, at most 0.6%, at most 0.7%, at most 0.8%, at most 0.9%, at most 1.0%, at most 1.1%, at most 1.2%, at most 1.3%, at most 1.4%, at most 1.5%, at most 1.6%, or at most 1.7% of the population of Fc domains of the FcRn antagonist molecules comprises sialic acid. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, or about 1.7% of the population of Fc domains of the FcRn antagonist molecules comprises sialic acid. In some embodiments, the population comprises or consists of FcRn antagonist molecules, and 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, or 1.7% of the population of FcRn antagonist molecule Fc domains comprise sialic acid. In some embodiments, the population comprises or consists of FcRn antagonist molecules, and 0.3% to 1.7%, 0.4% to 1.6%, or 0.5% to 1.5% of the population of FcRn antagonist molecule Fc domains comprise sialic acid. 【0138】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 38%, at least 39%, at least 40%, at least 41%, at least 42%, at least 43%, at least 44%, at least 45%, at least 46%, at least 47%, at least 48%, at least 49%, at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, or at least 57% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G0F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, or about 57% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G0F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, or 57% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G0F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 38% to 57%, 39% to 56%, or 40% to 55% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G0F N-glycan at EU position 297. 【0139】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 18%, at least 19%, at least 20%, at least 21%, at least 22%, at least 23%, at least 24%, at least 25%, at least 26%, or at least 27% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G1F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, or about 27% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G1F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, or 27% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G1F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 18% to 27%, 19% to 28%, or 20% to 25% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G1F N-glycan at EU position 297. 【0140】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, or at least 17% of the FcRn antagonist molecules comprise a first Fc domain comprising a G1F N-glycan at EU position 297 and a second Fc domain comprising a G1F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, or about 17% of the FcRn antagonist molecules comprise a first Fc domain comprising a G1F N-glycan at EU position 297 and a second Fc domain comprising a G1F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, or 17% of the FcRn antagonist molecules comprise a first Fc domain comprising a G1F N-glycan at EU position 297 and a second Fc domain comprising a G1F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 8% to 17%, 9% to 28%, or 10% to 15% of the FcRn antagonist molecules comprise a first Fc domain comprising a G1F N-glycan at EU position 297 and a second Fc domain comprising a G1F N-glycan at EU position 297. 【0141】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, or at least 17% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, or about 17% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, or 17% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 8% to 17%, 9% to 28%, or 10% to 15% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. 【0142】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, or at least 12% of the FcRn antagonist molecules comprise a first Fc domain comprising a G1F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, or about 12% of the FcRn antagonist molecules comprise a first Fc domain comprising a G1F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, or 12% of the FcRn antagonist molecules comprise a first Fc domain comprising a G1F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 3% to 12%, 4% to 11%, or 5% to 10% of the FcRn antagonist molecules comprise a first Fc domain comprising a G1F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. 【0143】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, or at least 6% of the FcRn antagonist molecules comprise a first Fc domain comprising a G2F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 1%, about 2%, about 3%, about 4%, about 5%, or about 6% of the FcRn antagonist molecules comprise a first Fc domain comprising a G2F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 1%, 2%, 3%, 4%, 5%, or 6% of the FcRn antagonist molecules comprise a first Fc domain comprising a G2F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 1% to 6%, 1% to 4%, or 2% to 4% of the FcRn antagonist molecules comprise a first Fc domain comprising a G2F N-glycan at EU position 297 and a second Fc domain comprising a G2F N-glycan at EU position 297. 【0144】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 2%, at least 3%, at least 4%, at least 5%, at least 6%, at least 7%, or at least 8% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G0 N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, or about 8% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G0 N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 2%, 3%, 4%, 5%, 6%, 7%, or 8% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G0 N-glycan at EU position 297. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 2% to 8%, 3% to 7%, or 4% to 6% of the FcRn antagonist molecules comprise a first Fc domain comprising a G0F N-glycan at EU position 297 and a second Fc domain comprising a G0 N-glycan at EU position 297. 【0145】 In some embodiments, the FcRn antagonist molecule lacks an amino acid at EU position 441 of one or both Fc domains. In some embodiments, the FcRn antagonist molecule comprises glycine and lysine at EU positions 440 and 441, respectively. In some embodiments, the FcRn antagonist molecule lacks amino acids at EU positions 440 and 441. In some embodiments, the FcRn antagonist molecule comprises an amidated proline at EU position 439. In some embodiments, the FcRn antagonist molecule comprises an amidated proline at EU position 439. In some embodiments, the FcRn antagonist molecule lacks amino acids at EU positions 440 and 441 and comprises an amidated proline at EU position 439. 【0146】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, or at least 97% of the Fc domains in the population lack an amino acid at EU position 441. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, or about 97% of the Fc domains in the population lack an amino acid at EU position 441. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, or 97% of the Fc domains in the population lack an amino acid at EU position 441. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 83% to 97%, 84% to 94%, or 85% to 95% of the Fc domains in the population lack an amino acid at EU position 441. 【0147】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein less than 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, or 17% of the Fc domains in the population have glycine and lysine, respectively, at EU positions 440 and 441. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, or 17% of the Fc domains in the population have glycine and lysine, respectively, at EU positions 440 and 441. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, or 17% of the Fc domains in the population have glycine and lysine, respectively, at EU positions 440 and 441. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 3% to 17%, 4% to 14%, or 5% to 15% of the Fc domains in the population have glycine and lysine, respectively, at EU positions 440 and 441. 【0148】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein less than 0.5%, less than 1.0%, less than 1.5%, or less than 2% of the Fc domains in the population lack amino acids at EU positions 440 and 441 and comprise an amidated proline at EU position 439. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 0.5%, about 1.0%, about 1.5%, or about 2% of the Fc domains in the population lack amino acids at EU positions 440 and 441 and comprise an amidated proline at EU position 439. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5%, 1.0%, 1.5%, or 2% of the Fc domains in the population lack amino acids at EU positions 440 and 441 and comprise an amidated proline at EU position 439. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5% to 2%, 0.5% to 1.5%, or 0.5% to 1.0% of the Fc domains in the population lack amino acids at EU positions 440 and 441 and comprise an amidated proline at EU position 439. 【0149】 In some embodiments, the FcRn antagonist molecule comprises aspartic acid, lysine, threonine, histidine, threonine, and cysteine ​​at EU positions 221, 222, 223, 224, 225, and 226, respectively. In some embodiments, the FcRn antagonist molecule lacks amino acids at EU position 221 and comprises lysine, threonine, histidine, threonine, and cysteine ​​at EU positions 222, 223, 224, 225, and 226, respectively. In some embodiments, the FcRn antagonist molecule lacks amino acids at EU positions 221 and 222 and comprises threonine, histidine, threonine, and cysteine ​​at EU positions 223, 224, 225, and 226, respectively. In some embodiments, the FcRn antagonist molecule lacks amino acids at EU positions 221-224 and has a threonine and a cysteine, respectively, at EU positions 225 and 226. In some embodiments, the FcRn antagonist molecule lacks amino acids at EU positions 221, 222, 223, 224, 225, and 226. 【0150】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the Fc domains in the population have aspartic acid, lysine, threonine, histidine, threonine, and cysteine ​​at EU positions 221, 222, 223, 224, 225, and 226, respectively. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% of the Fc domains in the population have aspartic acid, lysine, threonine, histidine, threonine, and cysteine ​​at EU positions 221, 222, 223, 224, 225, and 226, respectively. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the Fc domains in the population have aspartic acid, lysine, threonine, histidine, threonine, and cysteine ​​at EU positions 221, 222, 223, 224, 225, and 226, respectively. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 93% to 99%, 94% to 99%, or 95% to 99% of the Fc domains in the population have aspartic acid, lysine, threonine, histidine, threonine, and cysteine ​​at EU positions 221, 222, 223, 224, 225, and 226, respectively. 【0151】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein less than 0.5%, less than 1.0%, or less than 1.5% of the Fc domains in the population lack an amino acid at EU position 221 and have lysine, threonine, histidine, threonine, and cysteine, respectively, at EU positions 222, 223, 224, 225, and 226. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 0.5%, about 1.0%, or about 1.5% of the Fc domains in the population lack an amino acid at EU position 221 and have lysine, threonine, histidine, threonine, and cysteine, respectively, at EU positions 222, 223, 224, 225, and 226. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5%, 1.0%, or 1.5% of the Fc domains in the population lack an amino acid at EU position 221 and have lysine, threonine, histidine, threonine, and cysteine, respectively, at EU positions 222, 223, 224, 225, and 226. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5% to 1.0% of the Fc domains in the population lack an amino acid at EU position 221 and have lysine, threonine, histidine, threonine, and cysteine, respectively, at EU positions 222, 223, 224, 225, and 226. 【0152】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein less than 0.5%, less than 1.0%, or less than 1.5% of the Fc domains in the population lack amino acids at EU positions 221 and 222 and have threonine, histidine, threonine, and cysteine, respectively, at EU positions 223, 224, 225, and 226. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 0.5%, about 1.0%, or about 1.5% of the Fc domains in the population lack amino acids at EU positions 221 and 222 and have threonine, histidine, threonine, and cysteine, respectively, at EU positions 223, 224, 225, and 226. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5%, 1.0%, or 1.5% of the Fc domains in the population lack amino acids at EU positions 221 and 222 and have threonine, histidine, threonine, and cysteine, respectively, at EU positions 223, 224, 225, and 226. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5% to 1.0% of the Fc domains in the population lack amino acids at EU positions 221 and 222 and have threonine, histidine, threonine, and cysteine, respectively, at EU positions 223, 224, 225, and 226. 【0153】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein less than 0.5%, less than 1.0%, less than 1.5%, less than 2.5%, or less than 3.0% of the Fc domains in the population lack an amino acid at EU positions 221-224 and have a threonine and a cysteine, respectively, at EU positions 225 and 226. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 0.5%, about 1.0%, about 1.5%, about 2.5%, or about 3.0% of the Fc domains in the population lack an amino acid at EU positions 221-224 and have a threonine and a cysteine, respectively, at EU positions 225 and 226. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5%, 1.0%, 1.5%, 2.5%, or 3.0% of the Fc domains in the population lack amino acids at EU positions 221-224 and have threonine and cysteine, respectively, at EU positions 225 and 226. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5% to 1.0% of the Fc domains in the population lack amino acids at EU positions 221-224 and have threonine and cysteine, respectively, at EU positions 225 and 226. 【0154】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein less than 0.5%, less than 1.0%, or less than 1.5% of the Fc domains in the population lack amino acids at EU positions 221, 222, 223, 224, 225, and 226. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 0.5%, about 1.0%, or about 1.5% of the Fc domains in the population lack amino acids at EU positions 221, 222, 223, 224, 225, and 226. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5%, 1.0%, or 1.5% of the Fc domains in the population lack amino acids at EU positions 221, 222, 223, 224, 225, and 226. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5% to 1.0% of the Fc domains in the population lack amino acids at EU positions 221, 222, 223, 224, 225, and 226. 【0155】 In some embodiments, the FcRn antagonist molecules comprise an aspartic acid isomerization at EU position 280 or 401. In some embodiments, a population comprises or consists of FcRn antagonist molecules, and less than 0.5%, less than 1.0%, or less than 1.5% of the Fc domains in the population comprise an aspartic acid isomerization at EU position 280 or 401. In some embodiments, a population comprises or consists of FcRn antagonist molecules, and about 0.5%, about 1.0%, or about 1.5% of the Fc domains in the population comprise an aspartic acid isomerization at EU position 280 or 401. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5%, 1.0%, or 1.5% of the Fc domains in the population comprise an aspartic acid isomerization at EU position 280 or 401. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5% to 1.0% of the Fc domains in the population comprise an aspartic acid isomerization at EU position 280 or 401. 【0156】 In some embodiments, the FcRn antagonist molecule comprises an asparagine deamidation at EU position 384, 389, or 390. In some embodiments, the FcRn antagonist molecule comprises an asparagine deamidation at EU position 315. In some embodiments, the FcRn antagonist molecule comprises an asparagine deamidation at EU position 361. In some embodiments, the FcRn antagonist molecule comprises an asparagine deamidation at EU position 276 or 286. 【0157】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, and less than 8%, less than 9%, less than 10%, less than 11%, or less than 12% of the Fc domains in the population comprise asparagine deamidation at EU position 384, 389, or 390. In some embodiments, the population comprises or consists of FcRn antagonist molecules, and about 8%, about 9%, about 10%, about 11%, or about 12% of the Fc domains in the population comprise asparagine deamidation at EU position 384, 389, or 390. In some embodiments, the population comprises or consists of FcRn antagonist molecules, and 8%, 9%, 10%, 11%, or 12% of the Fc domains in the population comprise asparagine deamidation at EU position 384, 389, or 390. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 8% to 12%, 7% to 11%, or 8% to 10% of the Fc domains in the population comprise asparagine deamidation at EU position 384, 389, or 390. 【0158】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, and less than 1%, less than 2%, less than 3%, less than 4%, or less than 5% of the Fc domains in the population comprise asparagine deamidation at EU position 315. In some embodiments, the population comprises or consists of FcRn antagonist molecules, and about 1%, about 2%, about 3%, about 4%, or about 5% of the Fc domains in the population comprise asparagine deamidation at EU position 315. In some embodiments, the population comprises or consists of FcRn antagonist molecules, and 1%, 2%, 3%, 4%, or 5% of the Fc domains in the population comprise asparagine deamidation at EU position 315. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 1% to 5%, 2% to 4%, or 2% to 3% of the Fc domains in the population comprise asparagine deamidation at EU position 315. 【0159】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, and less than 1%, less than 2%, less than 3%, less than 4%, or less than 5% of the Fc domains in the population comprise asparagine deamidation at EU position 361. In some embodiments, the population comprises or consists of FcRn antagonist molecules, and about 1%, about 2%, about 3%, about 4%, or about 5% of the Fc domains in the population comprise asparagine deamidation at EU position 361. In some embodiments, the population comprises or consists of FcRn antagonist molecules, and 1%, 2%, 3%, 4%, or 5% of the Fc domains in the population comprise asparagine deamidation at EU position 361. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 1% to 5%, 2% to 4%, or 2% to 3% of the Fc domains in the population comprise asparagine deamidation at EU position 361. 【0160】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein less than 0.5%, less than 1.0%, or less than 1.5% of the Fc domains in the population comprise asparagine deamidation at EU position 276 or 286. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 0.5%, about 1.0%, or about 1.5% of the Fc domains in the population comprise asparagine deamidation at EU position 276 or 286. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5%, 1.0%, or 1.5% of the Fc domains in the population comprise asparagine deamidation at EU position 276 or 286. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5% to 1.0% of the Fc domains in the population comprise asparagine deamidation at EU position 276 or 286. 【0161】 In some embodiments, the FcRn antagonist molecule comprises an oxidation of methionine at EU position 428. In some embodiments, the FcRn antagonist molecule comprises an oxidation of tryptophan at EU position 277. 【0162】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein less than 3%, less than 4%, less than 5%, less than 6%, or less than 7% of the Fc domains in the population comprise an oxidized methionine at EU position 428. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 3%, about 4%, about 5%, about 6%, or about 7% of the Fc domains in the population comprise an oxidized methionine at EU position 428. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 3%, 4%, 5%, 6%, or 7% of the Fc domains in the population comprise an oxidized methionine at EU position 428. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 3% to 7%, 4% to 6%, or 4% to 5% of the Fc domains in the population have oxidized methionine at EU position 428. 【0163】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, and less than 0.5%, less than 1.0%, or less than 1.5% of the Fc domains in the population comprise oxidized tryptophan at EU position 277. In some embodiments, the population comprises or consists of FcRn antagonist molecules, and about 0.5%, about 1.0%, or about 1.5% of the Fc domains in the population comprise oxidized tryptophan at EU position 277. In some embodiments, the population comprises or consists of FcRn antagonist molecules, and 0.5%, 1.0%, or 1.5% of the Fc domains in the population comprise oxidized tryptophan at EU position 277. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5% to 1.0% of the Fc domains in the population comprise an oxidation of tryptophan at EU position 277. 【0164】 In some embodiments, the FcRn antagonist molecule comprises an amidation of proline at EU position 445. 【0165】 In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein less than 0.5%, less than 1.0%, or less than 1.5% of the Fc domains in the population comprise a proline amidation at EU position 445. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein about 0.5%, about 1.0%, or about 1.5% of the Fc domains in the population comprise a proline amidation at EU position 445. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5%, 1.0%, or 1.5% of the Fc domains in the population comprise a proline amidation at EU position 445. In some embodiments, the population comprises or consists of FcRn antagonist molecules, wherein 0.5% to 1.0% of the Fc domains in the population comprise a proline amidation at EU position 445. 【0166】 Polynucleotides, vectors, and production methods The present disclosure also provides polynucleotides encoding the FcRn antagonist molecules or fragments thereof disclosed herein. In some embodiments, the polynucleotides described herein are isolated or purified. As used herein, an "isolated" polynucleotide is one that is separated from other nucleic acid molecules, e.g., those present in the natural source of the polynucleotide (e.g., in a mouse or human), or is substantially free of other cellular material or culture medium when produced by recombinant techniques, or is substantially free of chemical precursors or other chemicals when chemically synthesized. The term "substantially free" includes, but is not limited to, polynucleotide preparations having less than about 15%, 10%, 5%, 2%, 1%, 0.5%, or 0.1% (particularly, less than about 10%) of other materials, e.g., cellular material, culture medium, other nucleic acid molecules, chemical precursors, and / or other chemicals. 【0167】 In one aspect, provided herein is a polynucleotide comprising a nucleotide sequence encoding an FcRn antagonist molecule described herein. In some embodiments, the polynucleotide comprises a nucleotide sequence encoding an Fc domain comprising an amino acid sequence at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 1-22. In some embodiments, the polynucleotide consists of a nucleotide sequence encoding an Fc domain comprising an amino acid sequence at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 1-22. 【0168】 In some embodiments, the polynucleotide comprises a nucleotide sequence encoding an Fc domain comprising the amino acid sequence of any one of SEQ ID NOs: 1 to 22. In some embodiments, the polynucleotide comprises a nucleotide sequence encoding an Fc domain consisting of the amino acid sequence of any one of SEQ ID NOs: 1 to 22. 【0169】 In some embodiments, the polynucleotide comprises a nucleotide sequence encoding two or more Fc domains. In some embodiments, the polynucleotide comprises a nucleotide sequence encoding two Fc domains. In some embodiments, the polynucleotide comprises a first nucleotide sequence encoding a first Fc domain and a second nucleotide sequence encoding a second Fc domain. In some embodiments, the first nucleotide sequence and the second nucleotide sequence are comprised in different nucleic acid molecules. In some embodiments, the first nucleotide sequence and the second nucleotide sequence are comprised in the same nucleic acid molecule. 【0170】 In some embodiments, the first and second nucleotide sequences encode the same Fc domain. In some embodiments, both the first and second nucleotide sequences encode an Fc domain comprising an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 5-20 and 22. In some embodiments, both the first and second nucleotide sequences encode an Fc domain consisting of an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 5-20 and 22. In some embodiments, both the first and second nucleotide sequences encode an Fc domain consisting of the amino acid sequence of any one of SEQ ID NOs: 5-20 and 22. 【0171】 In some embodiments, the first and second nucleotide sequences encode different Fc domains. In some embodiments, the first nucleotide sequence encodes an Fc domain comprising an amino acid sequence at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 1-22, and the second nucleotide sequence encodes a different Fc domain comprising an amino acid sequence at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 1-22. In some embodiments, a first nucleotide sequence encodes an Fc domain consisting of an amino acid sequence at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 1-22, and a second nucleotide sequence encodes a different Fc domain consisting of an amino acid sequence at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of any one of SEQ ID NOs: 1-22. In some embodiments, a first nucleotide sequence encodes an Fc domain comprising the amino acid sequence of any one of SEQ ID NOs: 1-22, and a second nucleotide sequence encodes a different Fc domain comprising the amino acid sequence of any one of SEQ ID NOs: 1-22. In some embodiments, the first nucleotide sequence encodes an Fc domain consisting of any one of the amino acid sequences of SEQ ID NOs: 1 to 22, and the second nucleotide sequence encodes a different Fc domain consisting of any one of the amino acid sequences of SEQ ID NOs: 1 to 22. 【0172】 Also provided herein are polynucleotides encoding the polypeptides provided above, which have been optimized, for example, by codon / RNA optimization, replacement with a heterologous signal sequence, and elimination of mRNA instability elements. Thus, methods for generating nucleic acids optimized for recombinant expression by introducing codon changes in mRNA and / or elimination of inhibitory regions can be performed by adapting the optimization methods described in, for example, U.S. Patent Nos. 5,965,726, 6,174,666, 6,291,664, 6,414,132, and 6,794,498, all of which are incorporated herein by reference in their entireties. For example, potential splice sites and instability elements (e.g., A / T or A / U-rich elements) within the RNA can be mutated without changing the amino acid encoded by the nucleic acid sequence to increase the stability of the RNA for recombinant expression. The alterations utilize the degeneracy of the genetic code, for example, by using alternative codons for the same amino acid. In one embodiment, it may be desirable to change one or more codons to encode a conservative variation, e.g., a similar amino acid having a similar chemical structure and properties and / or function as the native amino acid. 【0173】 Polynucleotides can be obtained by any method known in the art, and the nucleotide sequence of a polynucleotide can be determined by any method known in the art. Nucleotide sequences encoding the proteins described herein, and modified versions of these antibodies, can be determined using methods well known in the art, i.e., nucleotide codons known to encode specific amino acids are assembled to generate a nucleic acid encoding the protein. Such polynucleotides encoding proteins can be assembled from chemically synthesized oligonucleotides (e.g., as described in Kutmeier G et al., (1994) BioTechniques 17:242-6, which is incorporated herein by reference in its entirety), which briefly involves synthesizing overlapping oligonucleotides containing portions of the antibody-encoding sequence, annealing and ligating these oligonucleotides, and then amplifying the ligated oligonucleotides by PCR. 【0174】 Alternatively, polynucleotides encoding the proteins described herein can be generated from nucleic acid from a suitable source (e.g., a hybridoma) using methods well known in the art (e.g., PCR and other molecular cloning methods). For example, PCR amplification using synthetic primers hybridizable to the 3' and 5' ends of a known sequence can be performed using genomic DNA obtained from hybridoma cells producing the polypeptide of interest. Such PCR amplification methods can be used to obtain nucleic acid comprising a sequence encoding the polypeptide. The amplified nucleic acid can be cloned into a vector for expression in a host cell and further cloning. 【0175】 If a clone containing nucleic acid encoding a particular polypeptide is not available, but the sequence of the polypeptide is known, nucleic acid encoding the polypeptide may be chemically synthesized or obtained from a suitable source (e.g., a cDNA library generated from, or nucleic acid isolated therefrom, preferably polyA+ RNA, any tissue or cell that expresses a polypeptide described herein) by PCR amplification using synthetic primers hybridizable to the 3' and 5' ends of the sequence, or by cloning using oligonucleotide probes specific for the particular gene sequence, e.g., to identify cDNA clones from a cDNA library that encode the polypeptide. Amplified nucleic acids generated by PCR can then be cloned into replicable cloning vectors using any method well known in the art. 【0176】 DNA encoding the proteins described herein can be readily isolated and sequenced using conventional procedures. Hybridoma cells can serve as a source of such DNA. Once isolated, the DNA can be placed into an expression vector, which is then transfected into host cells, such as E. coli cells, monkey COS cells, Chinese hamster ovary (CHO) cells (e.g., CHO cells from the CHO GS System™ (Lonza)), or myeloma cells that do not otherwise produce the proteins described herein. 【0177】 Also provided are polynucleotides that hybridize under high stringency, intermediate or low stringency hybridization conditions to polynucleotides encoding the proteins described herein. 【0178】 Hybridization conditions are described in the art and are known to those skilled in the art. For example, hybridization under stringent conditions can include hybridization to filter-bound DNA in 6x sodium chloride / sodium citrate (SSC) at about 45°C, followed by one or more washes in 0.2x SSC / 0.1% SDS at about 50-65°C, and hybridization under highly stringent conditions can include hybridization to filter-bound nucleic acid in 6x SSC at about 45°C, followed by one or more washes in 0.1x SSC / 0.2% SDS at about 68°C. Hybridization under other stringent hybridization conditions is known to those skilled in the art and has been described, e.g., Ausubel FM et al., eds. (1989) Current Protocols in Molecular Biology, Vol. I, Green Publishing Associates, Inc. and John Wiley & Sons, Inc., New York, pages 6.3.1-6.3.6 and 2.10.3, which is incorporated herein by reference in its entirety. 【0179】 In one aspect, provided herein are cells (e.g., host cells), and associated polynucleotides and expression vectors, that express (e.g., recombinantly express) the proteins described herein. Provided herein are vectors (e.g., expression vectors) for recombinant expression in host cells, preferably mammalian cells (e.g., CHO cells), comprising a polynucleotide that includes a nucleotide sequence encoding a protein described herein. Also provided herein are host cells for recombinant expression of the proteins described herein, comprising such vectors. In one aspect, provided herein are methods for producing the proteins described herein, comprising expressing a polypeptide from a host cell. 【0180】 Recombinant expression of the proteins described herein generally involves the construction of an expression vector containing a polynucleotide encoding the polypeptide. Once a polynucleotide encoding a polypeptide described herein is obtained, a vector for producing the polypeptide can be produced by recombinant DNA technology using techniques well known in the art. Accordingly, methods for preparing a protein by expressing a polynucleotide containing a polypeptide-encoding nucleotide sequence are described herein. Methods well known to those skilled in the art can be used to construct expression vectors containing a polypeptide-encoding sequence and appropriate transcriptional and translational control signals. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. Also provided are replicable vectors containing a nucleotide sequence encoding a polypeptide described herein, wherein the nucleotide sequence is operably linked to a promoter. The expression vector can be transferred into cells (e.g., host cells) by conventional techniques, and the resulting cells can then be cultured by conventional techniques to produce the polypeptides described herein or fragments thereof. Thus, provided herein is a host cell containing a polynucleotide encoding a polypeptide described herein or a fragment thereof, or a heavy or light chain thereof, or a fragment thereof, or a single chain antibody described herein, wherein the polynucleotide is operably linked to a promoter for expression of such sequence in the host cell. 【0181】 In one embodiment, a host cell comprises a polynucleotide comprising one of the above first nucleotide sequences and one of the above second nucleotide sequences. In another embodiment, a host cell comprises a first polynucleotide comprising one of the above first nucleotide sequences and a second polynucleotide comprising one of the above first nucleotide sequences. In another embodiment, a host cell comprises a first vector comprising one of the above first nucleotide sequences and one of the above second nucleotide sequences. In another embodiment, a host cell comprises a first vector comprising one of the above first nucleotide sequences and one of the above second nucleotide sequences and a second vector comprising a second polynucleotide comprising one of the above first nucleotide sequences. 【0182】 In some embodiments, the Fc domain expressed by the first host cell associates with the Fc domain expressed by the second host cell to form an FcRn antagonist molecule. In some embodiments, provided herein is a population of host cells comprising such a first host cell and such a second host cell. 【0183】 In some embodiments, provided herein is a population of vectors comprising a first vector comprising a polynucleotide encoding an Fc domain and a second vector comprising a polynucleotide encoding an Fc domain. In some embodiments, provided herein is a population of vectors comprising a first vector comprising a polynucleotide encoding an Fc domain and a second vector comprising a polynucleotide encoding an Fc domain. In some embodiments, provided herein is a population of vectors comprising a first vector comprising a polynucleotide encoding an Fc domain and a polynucleotide encoding an Fc domain. In some embodiments, provided herein is a population of vectors comprising a first vector comprising polynucleotides encoding two Fc domains. 【0184】 A variety of host-expression vector systems can be used to express the polypeptides described herein (see, e.g., U.S. Pat. No. 5,807,715, which is incorporated herein by reference in its entirety). Such host-expression systems represent the vehicle in which a coding sequence of interest may be produced and subsequently purified, and also represent cells that, when transformed or transfected with the appropriate nucleotide coding sequence, are capable of expressing the polypeptides described herein in situ. These include microorganisms, such as bacteria (e.g., E. coli and B. subtilis), for example, bacteria transformed with a recombinant bacteriophage DNA, plasmid DNA, or cosmid DNA expression vector containing the antibody coding sequence; yeast (e.g., Saccharomyces and Pichia), for example, yeast transformed with a recombinant yeast expression vector containing the antibody coding sequence; insect cell lines, for example, insect cell lines infected with a recombinant viral expression vector (e.g., baculovirus) containing the antibody coding sequence; plant cell lines (e.g., green algae, e.g., Chlamydomonas reinhardtii), for example, plant cell lines infected with a recombinant viral expression vector (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV), or plant cell lines transformed with a recombinant plasmid expression vector (e.g., Ti plasmid) containing the antibody coding sequence; or mammalian cell lines (e.g., COS (e.g., COS1 or COS), CHO, BHK, MDCK, HEK 293, NS0, PER.C6, VERO, CRL7O3O, HsS78Bst, HeLa, NIH 3T3, HEK-293T, HepG2, SP210, R1.1, BW, LM, BSC1, BSC40, YB / 20, and BMT10 cells), for example, mammalian cell lines harboring recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or promoters derived from mammalian viruses (e.g., adenovirus late promoter, vaccinia virus 7.5K promoter).In one embodiment, cells for expressing an antibody described herein are Chinese hamster ovary (CHO) cells, e.g., CHO cells from the CHO GS System™ (Lonza). In one embodiment, the heavy and / or light chains of an antibody produced by a CHO cell may have an N-terminal glutamine or glutamic acid residue replaced by pyroglutamic acid. In one embodiment, cells for expressing a polypeptide described herein are human cells, e.g., a human cell line. In one embodiment, the mammalian expression vector is pOptiVEC™ or pcDNA3.3. In one embodiment, bacterial cells, e.g., Escherichia coli, or eukaryotic cells (e.g., mammalian cells) are used for expression of recombinant polypeptides. For example, mammalian cells, e.g., CHO cells, together with vectors such as the major intermediate-early gene promoter element from human cytomegalovirus, are effective expression systems for antibodies (Foecking MK & Hofstetter H, (1986) Gene 45:101-5, and Cockett MI et al., (1990) Biotechnology 8(7):662-7, each of which is incorporated herein by reference in its entirety). In one embodiment, the polypeptides described herein are produced by CHO cells or NSO cells. In one embodiment, expression of the nucleotide sequence encoding the polypeptides described herein comprising one, two, or three binding sites to human FcRn is regulated by a constitutive promoter, an inducible promoter, or a tissue-specific promoter. 【0185】 In bacterial systems, several expression vectors may be advantageously selected for the expression of the antibody molecule depending on the use intended for the antibody molecule. For example, vectors which direct the expression of high levels of fusion protein products that are easily purified may be desirable when large quantities of such polypeptides are produced for the generation of pharmaceutical compositions of the antibody molecule. Such vectors include, but are not limited to, the E. coli expression vector pUR278 (Ruether U & Mueller-Hill B, (1983) EMBO J 2:1791-1794), in which coding sequences can be individually ligated into the vector in frame with the lac Z coding region to produce a fusion protein; and the pIN vector (Inouye S & Inouye M, (1985) Nuc Acids Res 13:3101-3109; Van Heeke G & Schuster SM, (1989) J Biol Chem 24:5503-5509), all of which are incorporated herein by reference in their entireties. Also, for example, pGEX vectors can be used to express foreign polypeptides as fusion proteins with glutathione 5-transferase (GST). In general, such fusion proteins are soluble and can easily be purified from lysed cells by adsorption and binding to matrix glutathione agarose beads, followed by elution in the presence of free glutathione. The pGEX vectors are designed to contain thrombin or factor Xa protease cleavage sites so that the cloned target gene product can be released from the GST moiety. 【0186】 In an insect system, for example, Autographa californica nuclear polyhedrosis virus (AcNPV) can be used as a vector to express foreign genes. The virus grows in Spodoptera frugiperda cells. Coding sequences can be cloned individually into non-essential regions of the virus (e.g., the polyhedrin gene) and placed under control of an AcNPV promoter (e.g., the polyhedrin promoter). 【0187】 Several viral-based expression systems can be used in mammalian host cells. When adenovirus is used as an expression vector, the coding sequence of interest can be ligated to an adenovirus transcription / translation control complex, e.g., the late promoter and tripartite leader sequence. This chimeric gene can then be inserted into the adenovirus genome by in vitro or in vivo recombination. Insertion into a non-essential region of the viral genome (e.g., region E1 or E3) results in a recombinant virus that is viable and capable of expressing the molecule in infected hosts (see, e.g., Logan J & Shenk T, (1984) PNAS 81(12):3655-9, incorporated herein by reference in its entirety). Specific initiation signals may also be required for efficient translation of the inserted coding sequence. These signals include the ATG initiation codon and adjacent sequences. Furthermore, the initiation codon must be in phase with the reading frame of the desired coding sequence to ensure translation of the entire insert. These exogenous translational control signals and initiation codons can be of a variety of origins, both natural and synthetic. The efficiency of expression can be enhanced by the inclusion of appropriate transcription enhancer elements, transcription terminators, etc. (see, e.g., Bitter G et al., (1987) Methods Enzymol. 153:516-544, which is incorporated herein by reference in its entirety). 【0188】 In addition, a host cell strain may be chosen that modulates the expression of the inserted sequences, or modifies and processes the gene product in the specific fashion desired. Such modifications (e.g., glycosylation) and processing (e.g., cleavage) of protein products may be important for the function of the protein. Different host cells have characteristic and specific mechanisms for the post-translational processing and modification of proteins and gene products. An appropriate cell line or host system may be selected to ensure the correct modification and processing of the expressed foreign protein. To this end, eukaryotic host cells that possess the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the gene product may be used. Such mammalian host cells include, but are not limited to, CHO, VERO, BHK, HeLa, MDCK, HEK 293, NIH 3T3, W138, BT483, Hs578T, HTB2, BT2O, T47D, NS0 (a mouse myeloma cell line that does not endogenously produce any immunoglobulin chains), CRL7O3O, COS (e.g., COS1 or COS), PER.C6, VERO, HsS78Bst, HEK-293T, HepG2, SP210, R1.1, BW, LM, BSC1, BSC40, YB / 20, BMT10, and HsS78Bst cells. In one embodiment, the proteins described herein are produced in mammalian cells, e.g., CHO cells. 【0189】 In one embodiment, the polypeptides described herein comprise portions of antibodies with reduced or no fucose content. Such proteins can be produced using techniques known to those skilled in the art. For example, proteins can be expressed in cells that are deficient or lack the ability to fucosylate. In one example, a cell line with knockout of both alleles of α1,6-fucosyltransferase can be used to produce antibodies with reduced fucose content. The Potelligent® system (Lonza) is an example of such a system that can be used to produce antibodies with reduced fucose content. 【0190】 For long-term, high-yield production of recombinant proteins, stable expression cells can be generated. For example, cell lines that stably express the proteins described herein can be engineered. In one embodiment, the cells provided herein stably express FcRn antagonist molecules. 【0191】 In certain embodiments, rather than using expression vectors containing viral origins of replication, host cells can be transformed with DNA controlled by appropriate expression control elements (e.g., promoters, enhancers, sequences, transcription terminators, polyadenylation sites, etc.) and a selectable marker. After introduction of the foreign DNA / polynucleotide, engineered cells can be allowed to grow in an enriched medium for 1-2 days and then switched to a selective medium. The selectable marker on the recombinant plasmid confers resistance to selection, allowing cells to stably integrate the plasmid into their chromosomes and grow to form foci, which can then be cloned and expanded into cell lines. This method can advantageously be used to engineer cell lines that express polypeptides containing one, two, or three binding sites to human FcRn or fragments thereof described herein. Such engineered cell lines can be particularly useful in screening and evaluation of compositions that interact directly or indirectly with the polypeptides. 【0192】 Several selection systems can be used, including, but not limited to, herpes simplex virus thymidine kinase (Wigler M et al., (1977) Cell 11(1):223-32); hypoxanthine guanine phosphoribosyltransferase (Szybalska EH & Szybalski W, (1962) PNAS 48(12):2026-2034); and adenine phosphoribosyltransferase (Lowy I et al., (1980) Cell 22(3):817-23) genes in tk, hgprt, or aprt cells, respectively, all of which are incorporated herein by reference in their entireties. Furthermore, antimetabolite resistance is mediated by the following genes: dhfr, which confers resistance to methotrexate (Wigler M et al., (1980) PNAS 77(6):3567-70; O'Hare K et al., (1981) PNAS 78:1527-31); gpt, which confers resistance to mycophenolic acid (Mulligan RC & Berg P, (1981) PNAS 78(4):2072-6); neo, which confers resistance to the aminoglycoside G-418 (Wu GY & Wu CH, (1991) Biotherapy 3:87-95; Tolstoshev P, (1993) Ann Rev Pharmacol Toxicol 32:573-596; Mulligan RC, (1993) Science 260:926-932; and Morgan RA & Anderson WF, (1993) Ann Rev Biochem 62:191-217; Nabel GJ & Felgner PL, (1993) Trends Biotechnol 11(5):211-5); and hygro, which confers resistance to hygromycin (Santerre RF et al., (1984) Gene 30(1-3):147-56), all of which are incorporated herein by reference in their entireties.Methods generally known in the art of recombinant DNA technology can be routinely applied to select the desired recombinant clones, and such methods are described, for example, in Ausubel FM et al., (eds.), Current Protocols in Molecular Biology, John Wiley & Sons, NY (1993), Kriegler M, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY (1990), and Chapters 12 and 13, Dracopoli NC et al., (eds.), Current Protocols in Human Genetics, John Wiley & Sons, NY (1994), Colbere-Garapin F et al., (1981) J Mol Biol 150:1-14, all of which are incorporated herein by reference in their entirety. 【0193】 Polypeptide expression levels can be increased by vector amplification (for a review, see Bebbington CR & Hentschel CCG, The use of vectors based on gene amplification for the expression of cloned genes in mammalian cells in DNA cloning, p. 163-188. DNA Cloning, Vol. III, A Practical Approach. D.M.Glover (ed.) (Academic Press, New York, 1987), which is incorporated herein by reference in its entirety). When the marker in the vector system is amplifiable, an increase in the level of inhibitor present in the host cell culture increases the number of copies of the marker gene. Also, because the amplified region is associated with the gene of interest, production of the polypeptide increases (Crouse GF et al., (1983) Mol Cell Biol 3:257-66, which is incorporated herein by reference in its entirety). 【0194】 Host cells can be co-transfected with two or more expression vectors described herein. The two vectors can contain identical selectable markers, which allow for equal expression of heavy and light chain polypeptides. Host cells can be co-transfected with different amounts of two or more expression vectors. For example, host cells can be transfected with any one of the following ratios of the first expression vector to the second expression vector: approximately 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:12, 1:15, 1:20, 1:25, 1:30, 1:35, 1:40, 1:45, or 1:50. 【0195】 Alternatively, a single vector capable of encoding and expressing both polypeptides can be used. The coding sequence can comprise cDNA or genomic DNA. Expression vectors can be monocistronic or multicistronic. A multicistronic nucleic acid construct can encode 2, 3, 4, 5, 6, 7, 8, 9, 10, or more genes / nucleotide sequences, or 2-5, 5-10, or 10-20 genes / nucleotide sequences. For example, a bicistronic nucleic acid construct can comprise a promoter, a first gene, and a second gene in the following order: In such an expression vector, transcription of both genes can be driven by a promoter, translation of mRNA from the first gene can be via a cap-dependent scanning mechanism, and translation of mRNA from the second gene can be via a cap-independent mechanism, e.g., an IRES. 【0196】 The polypeptides described herein, when produced by recombinant expression, can be purified by any method known in the art for the purification of proteins, for example, chromatography (e.g., ion exchange, affinity, particularly affinity to specific antigens following Protein A, and sizing column chromatography), centrifugation, differential solubility, or any other standard technique for the purification of proteins. Additionally, the polypeptides described herein can be fused to heterologous polypeptide sequences described herein or otherwise known in the art to facilitate purification. 【0197】 In one embodiment, the polypeptides described herein are isolated or purified. In one embodiment, an isolated polypeptide is substantially free of other polypeptides having antigenic specificities different from the isolated polypeptide. For example, in certain embodiments, preparations of the proteins described herein are substantially free of cellular material and / or chemical precursors. The term "substantially free of cellular material" includes preparations of a polypeptide in which the polypeptide is isolated from cellular components of the cells from which it is isolated or recombinantly produced. Thus, a polypeptide that is substantially free of cellular material includes preparations of a polypeptide having less than about 30%, 20%, 10%, 5%, 2%, 1%, 0.5%, or 0.1% (by dry weight) of heterologous proteins (also referred to herein as "contaminating proteins") and / or variants of the polypeptide, e.g., different post-translationally modified forms of the polypeptide or other different versions of the polypeptide (e.g., polypeptide fragments). Additionally, when recombinantly produced, the polypeptides are generally substantially free of culture medium, i.e., culture medium represents less than about 20%, 10%, 2%, 1%, 0.5%, or 0.1% of the volume of the protein preparation. When produced by chemical synthesis, the polypeptides are generally substantially free of chemical precursors or other chemicals, i.e., separated from chemical precursors or other chemicals involved in the synthesis of the protein. Thus, such preparations of protein have less than about 30%, 20%, 10%, or 5% (by dry weight) of chemical precursors or compounds other than the protein of interest. In one embodiment, the polypeptides described herein are isolated or purified. 【0198】 The polypeptides described herein can be produced by any method known in the art for the synthesis of antibodies, for example, chemical synthesis or recombinant expression techniques. The methods described herein employ, unless otherwise indicated, conventional techniques of molecular biology, microbiology, genetic analysis, recombinant DNA, organic chemistry, biochemistry, PCR, oligonucleotide synthesis and modification, nucleic acid hybridization, and related fields within the art. These techniques are described, for example, in the references cited herein and are explained more fully in the literature.See, for example, Maniatis T et al., (1982) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press; Sambrook J et al., (1989) Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor Laboratory Press; Sambrook J et al., (2001) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Ausubel FM et al., Current Protocols in Molecular Biology, John Wiley & Sons (1987 and annually updated editions); Current Protocols in Immunology, John Wiley & Sons (1987 and annually updated editions); Gait (ed.) (1984) Oligonucleotide Synthesis: A Practical Approach, IRL Press; Eckstein (ed.) (1991) Oligonucleotides and Analogues: A Practical Approach, IRL Press; Birren B et al. al., (eds.) (1999) Genome Analysis: A Laboratory Manual, Cold Spring Harbor Laboratory Press, all of which are incorporated herein by reference in their entireties. 【0199】 In one embodiment, a polypeptide described herein is prepared, expressed, produced, or isolated by any means, including production, e.g., via synthesis, genetic engineering of DNA sequences. In one embodiment, such a polypeptide comprises a sequence (e.g., a DNA sequence or an amino acid sequence) that does not naturally occur within the antibody germline repertoire of an animal or mammal (e.g., a human) in vivo. 【0200】 Pharmaceutical Compositions In one aspect, the present disclosure provides pharmaceutical compositions comprising the FcRn antagonist molecules disclosed herein for use in methods for treating antibody-mediated disorders (e.g., autoantibody-mediated disorders). Generally, these FcRn antagonist molecules inhibit the binding of Fc-containing agents (e.g., antibodies and immunoadhesins) to FcRn in vivo, which results in an increased degradation rate of the Fc-containing agents and, concomitantly, reduced serum levels of these agents. 【0201】 In some embodiments, the FcRn antagonist molecules of the present disclosure have a predicted molecular weight in the range of about 50 kDa to about 57 kDa. In some embodiments, the average molecular weight of unaggregated FcRn antagonist molecules in the population is 50 kDa to 57 kDa, 51 kDa to 56 kDa, 52 kDa to 55 kDa, 54 kDa to 55 kDa, or 54.4 kDa to 54.7 kDa. In some embodiments, the average molecular weight of unaggregated FcRn antagonist molecules in the population is about 50 kDa, about 51 kDa, about 52 kDa, about 53 kDa, about 54 kDa, about 55 kDa, about 56 kDa, or about 57 kDa. In some embodiments, the average molecular weight of the unaggregated FcRn antagonist molecules in the population is 50 kDa, 51 kDa, 52 kDa, 53 kDa, 54 kDa, 55 kDa, 56 kDa, or 57 kDa, or about 54.0 kDa, about 54.1 kDa, about 54.2 kDa, about 54.3 kDa, about 54.4 kDa, about 54.5 kDa, about 54.6 kDa, about 54.7 kDa, about 54.8 kDa, or about 54.9 kDa. In some embodiments, the average molecular weight of the unaggregated FcRn antagonist molecules in the population is 54.0 kDa, 54.1 kDa, 54.2 kDa, 54.3 kDa, 54.4 kDa, 54.5 kDa, 54.6 kDa, 54.7 kDa, 54.8 kDa, or 54.9 kDa. 【0202】 In some embodiments, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, or 1.0% of the FcRn antagonist molecules in the population are aggregated. In some embodiments, about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, or 1.0% of the FcRn antagonist molecules in the population are aggregated. In some embodiments, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, or 1.0% of the FcRn antagonist molecules in the population are aggregated. In some embodiments, 0.1% to 1.0%, 0.3% to 0.8%, 0.4% to 0.6%, or 0.3% to 0.5% of the FcRn antagonist molecules in the population are aggregated. 【0203】 In some embodiments, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of the dimers in a population of FcRn antagonist molecules are linked by at least one disulfide bond. In some embodiments, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% of the dimers in a population of FcRn antagonist molecules are linked by at least one disulfide bond. In some embodiments, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the dimers in a population of FcRn antagonist molecules are linked by at least one disulfide bond. In some embodiments, 90% to 99%, 92% to 97%, 94% to 96%, or 93% to 95% of the dimers in a population of FcRn antagonist molecules are linked by at least one disulfide bond. 【0204】 In some embodiments, 0.2%, 0.4%, 0.6%, 0.8%, 1.0%, 1.2%, 1.4%, 1.6%, 1.8%, or 2.0% of the FcRn antagonist molecules in a population have free thiol groups. In some embodiments, about 0.2%, 0.4%, 0.6%, 0.8%, 1.0%, 1.2%, 1.4%, 1.6%, 1.8%, or 2.0% of the FcRn antagonist molecules in a population have free thiol groups. In some embodiments, 0.2%, 0.4%, 0.6%, 0.8%, 1.0%, 1.2%, 1.4%, 1.6%, 1.8%, or 2.0% of the FcRn antagonist molecules in a population have free thiol groups. In some embodiments, 0.2% to 2.0%, 0.6% to 1.6%, 0.8% to 1.2%, or 0.7% to 1.0% of the FcRn antagonist molecules in the population have a free thiol group. 【0205】 In some embodiments, the FcRn antagonist molecule is administered intravenously (IV) or subcutaneously (SC). 【0206】 For IV administration, in certain embodiments, the FcRn antagonist molecule may be administered in a formulation comprising sodium phosphate, sodium chloride, L-arginine hydrochloride, and polysorbate 80. In certain embodiments, the FcRn antagonist molecule may be administered in a formulation comprising about 25 mM sodium phosphate, about 100 mM sodium chloride, and about 150 mM L-arginine hydrochloride (pH 6.7), and about 0.02% (w / v) polysorbate 80. In certain embodiments, the FcRn antagonist molecule may be administered in a formulation comprising 25 mM sodium phosphate, 100 mM sodium chloride, and 150 mM L-arginine hydrochloride (pH 6.7), and 0.02% (w / v) polysorbate 80. In certain embodiments, the FcRn antagonist molecule can be administered via intravenous infusion in a total volume of about 250 mL over a period of about 2 hours in a formulation comprising about 25 mM sodium phosphate, about 100 mM sodium chloride, and about 150 mM L-arginine hydrochloride (pH 6.7), and about 0.02% (w / v) polysorbate 80. In certain embodiments, the FcRn antagonist molecule can be administered via intravenous infusion in a total volume of 250 mL over a period of about 2 hours in a formulation comprising 25 mM sodium phosphate, 100 mM sodium chloride, and 150 mM L-arginine hydrochloride (pH 6.7), and 0.02% (w / v) polysorbate 80. See, e.g., WO2019 / 110823A1, which is incorporated herein by reference in its entirety. 【0207】 In certain embodiments, the FcRn antagonist molecule may be administered over a period of about 1 hour in a formulation comprising an aqueous solution having a pH of about 6.7, comprising about 25 mM sodium phosphate, about 100 mM sodium chloride, and about 150 mM L-arginine hydrochloride, and about 0.02% (w / v) polysorbate 80, diluted to a total volume of about 125 mL for intravenous infusion. In certain embodiments, the FcRn antagonist molecule may be administered over a period of 1 hour in a formulation comprising an aqueous solution having a pH of 6.7, comprising 25 mM sodium phosphate, 100 mM sodium chloride, and 150 mM L-arginine hydrochloride, and 0.02% (w / v) polysorbate 80, diluted to a total volume of 125 mL for intravenous infusion. 【0208】 In certain embodiments, the FcRn antagonist molecule may be administered in a formulation comprising an aqueous solution having a pH of about 6.7, the aqueous solution comprising about 4 mM sodium phosphate, about 146 mM sodium chloride, about 24 mM L-arginine, and about 0.0032% (w / v) polysorbate 80. This formulation is administered via intravenous infusion in a total volume of about 125 mL over a period of about 1 hour. In certain embodiments, the FcRn antagonist molecule may be administered in a formulation comprising an aqueous solution having a pH of 6.7, the aqueous solution comprising 4 mM sodium phosphate, 146 mM sodium chloride, 24 mM L-arginine, and 0.0032% (w / v) polysorbate 80. This formulation is administered via intravenous infusion in a total volume of 125 mL over a period of 1 hour. 【0209】 In certain embodiments, the FcRn antagonist molecule may be administered via IV infusion and is provided in a sterile, clear, concentrated solution at a concentration of about 20 mg / mL. In certain embodiments, the FcRn antagonist molecule may be administered via IV infusion and is provided in a sterile, clear, concentrated solution at a concentration of 20 mg / mL. 【0210】 In certain embodiments, the FcRn antagonist molecule may be administered via IV infusion and is provided in a vial (e.g., a single-dose vial). In certain embodiments, the FcRn antagonist molecule vial contains about 400 mg of the FcRn antagonist molecule at a concentration of about 20 mg / mL. In certain embodiments, the FcRn antagonist molecule vial contains 400 mg of the FcRn antagonist molecule at a concentration of 20 mg / mL. In certain embodiments, each mL of solution in the FcRn antagonist molecule vial contains about 31.6 mg of L-arginine hydrochloride, about 0.2 mg of polysorbate 80, about 5.8 mg of sodium chloride, about 2.4 mg of sodium phosphate dibasic anhydrous, about 1.1 mg of sodium phosphate monobasic monohydrate, and water for injection, USP, at a pH of about 6.7. In certain embodiments, each mL of solution in a vial of FcRn antagonist molecule contains 31.6 mg of L-arginine hydrochloride, 0.2 mg of polysorbate 80, 5.8 mg of sodium chloride, 2.4 mg of sodium phosphate dibasic anhydrous, 1.1 mg of sodium phosphate monobasic monohydrate, and water for injection, USP, at a pH of 6.7. 【0211】 In certain embodiments, for patients weighing less than 120 kg, the FcRn antagonist molecule may be administered as an IV infusion at a dose of about 10 mg / kg. In certain embodiments, for patients weighing less than 120 kg, the FcRn antagonist molecule may be administered as an IV infusion at a dose of about 10 mg / kg over about 1 hour. In certain embodiments, for patients weighing less than 120 kg, the FcRn antagonist molecule may be administered as an IV infusion at a dose of about 10 mg / kg over about 1 hour once a week. In certain embodiments, for patients weighing less than 120 kg, the FcRn antagonist molecule may be administered as an IV infusion at a dose of about 10 mg / kg over about 1 hour once a week for about 4 weeks. In certain embodiments, for patients weighing less than 120 kg, the FcRn antagonist molecule may be administered as an IV infusion at a dose of 10 mg / kg. In certain embodiments, for patients weighing less than 120 kg, the FcRn antagonist molecule may be administered at a dose of 10 mg / kg via IV infusion over one hour. In certain embodiments, for patients weighing less than 120 kg, the FcRn antagonist molecule may be administered at a dose of 10 mg / kg via IV infusion over one hour once a week. In certain embodiments, for patients weighing less than 120 kg, the FcRn antagonist molecule may be administered at a dose of 10 mg / kg via IV infusion over one hour once a week for four weeks. In certain embodiments, for patients weighing 120 kg or more, the FcRn antagonist molecule may be administered at a dose of about 1200 mg per IV infusion. In certain embodiments, for patients weighing 120 kg or more, the FcRn antagonist molecule may be administered at a dose of 1200 mg per IV infusion. 【0212】 For SC administration, in certain embodiments, the FcRn antagonist molecule may be administered alone. Alternatively, for SC administration, in certain embodiments, the FcRn antagonist molecule may be co-formulated with a hyaluronidase, such as, in particular, rHuPH20, and administered. Co-formulated materials may allow for larger volumes of SC administration. 【0213】 In some embodiments, the FcRn antagonist molecule may be administered in a formulation comprising an aqueous solution comprising about 20 mM L-histidine, about 100 mM sodium chloride, about 60 mM sucrose, about 10 mM L-methionine, and about 0.04% (w / v) polysorbate 20, wherein the composition has a pH of about 6.0. In some embodiments, the formulation comprises about 180 mg / mL of the FcRn antagonist molecule. In some embodiments, the FcRn antagonist molecule may be administered in a formulation comprising an aqueous solution comprising 20 mM L-histidine, 100 mM sodium chloride, 60 mM sucrose, 10 mM L-methionine, and 0.04% (w / v) polysorbate 20, wherein the composition has a pH of 6.0. In some embodiments, the formulation comprises 180 mg / mL of the FcRn antagonist molecule. 【0214】 In some embodiments, the FcRn antagonist molecule may be administered in a formulation comprising an aqueous solution comprising about 20 mM L-histidine, about 50 mM L-arginine, about 100 mM sodium chloride, about 60 mM sucrose, about 10 mM L-methionine, and about 0.04% (w / v) polysorbate 80, wherein the composition has a pH of about 6.0. In some embodiments, the formulation comprises about 200 mg / mL of the FcRn antagonist molecule. In some embodiments, the FcRn antagonist molecule may be administered in a formulation comprising an aqueous solution comprising 20 mM L-histidine, 50 mM L-arginine, 100 mM sodium chloride, 60 mM sucrose, 10 mM L-methionine, and 0.04% (w / v) polysorbate 80, wherein the composition has a pH of 6.0. In some embodiments, the formulation comprises 200 mg / mL of the FcRn antagonist molecule. 【0215】 The formulations disclosed herein include bulk drug compositions useful for manufacturing pharmaceutical compositions (e.g., compositions suitable for administration to a subject or patient) that can be used to prepare unit dosage forms. In one embodiment, the compositions of the invention are pharmaceutical compositions. Such compositions comprise a prophylactically or therapeutically effective amount of one or more prophylactic or therapeutic agents of the invention (e.g., FcRn antagonist molecules) (or other prophylactic or therapeutic agents) and a pharmaceutically acceptable carrier. 【0216】 In some embodiments, the pharmaceutical composition is formulated for administration to a subject via any suitable route of administration, including, but not limited to, intramuscular, intravenous, intradermal, intraperitoneal, subcutaneous, epidural, nasal, oral, rectal, topical, inhalation, buccal (e.g., sublingual), and transdermal administration. In one embodiment, the pharmaceutical composition is formulated to be suitable for intravenous administration to a subject. In one embodiment, the pharmaceutical composition is formulated to be suitable for subcutaneous administration to a subject. 【0217】 Treatment method In one embodiment, the FcRn antagonist molecule antagonizes FcRn binding to the antibody Fc region. The present disclosure provides a method for reducing serum IgG in a subject, comprising administering to the subject a therapeutically effective amount of an FcRn antagonist molecule according to the present disclosure or a pharmaceutical composition comprising the same. In one embodiment, the level of serum IgG is reduced in the subject after administration of the FcRn antagonist molecule compared to the baseline level of serum IgG. In one embodiment, a total serum IgG reduction of about 60% is achieved compared to the baseline serum IgG level. In one embodiment, a total serum IgG reduction of about 65%, about 70%, about 75%, or about 80% is achieved compared to the baseline serum IgG level. In one embodiment, a total serum IgG reduction of about 65% is achieved compared to the baseline serum IgG level. In one embodiment, a total serum IgG reduction of about 70% is achieved compared to the baseline serum IgG level. In one embodiment, a total serum IgG reduction of about 75% is achieved compared to the baseline serum IgG level. In one embodiment, a total serum IgG reduction of about 80% is achieved compared to the baseline serum IgG level. 【0218】 In one embodiment, the level of FcRn is not decreased in a subject after administration of an FcRn antagonist molecule compared to the baseline level of FcRn. In one embodiment, an FcRn reduction of less than about 1%, 2%, 3%, 4%, or 5% is observed compared to the baseline FcRn level. In one embodiment, an FcRn reduction of less than about 10% is observed compared to the baseline FcRn level. 【0219】 The present disclosure also provides a method for treating an antibody-mediated disorder (e.g., an autoantibody-mediated disorder) in a subject, comprising administering to the subject a therapeutically effective amount of an FcRn antagonist molecule according to the present disclosure or a pharmaceutical composition comprising the same. 【0220】 In some embodiments, the antibody-mediated disorder is an autoimmune disease. In some embodiments, the autoimmune disease is selected from the group consisting of pancreatic islet allograft rejection, alopecia areata, ankylosing spondylitis, antiphospholipid syndrome, autoimmune Addison's disease, Alzheimer's disease, antineutrophil cytoplasmic autoantibodies (ANCA), autoimmune disease of the adrenal gland, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune myocarditis, autoimmune neutropenia, autoimmune oophoritis and orchitis, immune thrombocytopenia (ITP or idiopathic thrombocytopenic purpura), and idiopathic thrombocytopenic purpura.purpura), immune-mediated thrombocytopenia, or primary immune thrombocytopenia), autoimmune urticaria, Behçet's disease, bullous pemphigoid (BP), cardiomyopathy, Castleman's disease, celiac sprue dermatitis, chronic fatigue and immune dysfunction syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), Churg-Strauss syndrome, cicatricial pemphigoid, CREST syndrome, cold agglutinin disease, Crohn's disease, dilated cardiomyopathy, discoid lupus, epidermolysis bullosa acquisita, essential mixed cryoglobulinemia, factor VIII deficiency fibromyalgia-fibromyositis, glomerulonephritis, Graves' disease, Guillain-Barré syndrome, Goodpasture's syndrome, graft-versus-host disease (GVHD), Hashimoto's thyroiditis, hemophilia A, idiopathic inflammatory myopathy (IIM), idiopathic membranous neuropathy, idiopathic pulmonary fibrosis, IgA neuropathy, IgM polyneuropathy, immune-mediated necrotizing myopathy (IMNM), juvenile arthritis, Kawasaki disease, lichen planus, lichen sclerosus, lupus erythematosus, lupus nephritis, Meniere's disease, mixed connective tissue disease, mucous membrane pemphigoid, multiple myeloma Sclerosis, type 1 diabetes, multifocal motor neuropathy (MMN), myasthenia gravis (MG), generalized myasthenia gravis (gMG), myositis, paraneoplastic bullous pemphigoid, gestational pemphigoid, pemphigoid vulgaris (PV), pemphigus foliaceus (PF), pernicious anemia, polyarteritis nodosa, polychondritis, polyglandular syndrome, polymyalgia rheumatica, polymyositis, dermatomyositis (DM), necrotizing autoimmune myopathy (NAM), antisynthetase syndrome (ASyS), primary agammaglobulinemia, primary biliary cirrhosis, psoriasis, psoriatic arthritis arthritis, relapsing polychondritis, Raynaud's phenomenon, Reiter's syndrome, rheumatoid arthritis, sarcoidosis, scleroderma, Sjogren's syndrome, solid organ transplant rejection, stiff-body syndrome, systemic lupus erythematosus, Takayasu's arteritis, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), temporal arteritis / giant cell arteritis, thrombotic thrombocytopenic purpura, ulcerative colitis, uveitis, dermatitis herpetiformis vasculitis, antineutrophil cytoplasmic antibody-associated vasculitis, vitiligo, and Wegener's granulomatosis. 【0221】 In one embodiment, at least one of the IgG subtypes is reduced in a subject after administration of an FcRn antagonist molecule. In one embodiment, at least one of the IgG subtypes is reduced in the serum of a subject after administration of an FcRn antagonist molecule. In one embodiment, IgG1 is reduced. In one embodiment, IgG2 is reduced. In one embodiment, IgG3 is reduced. In one embodiment, IgG4 is reduced. In some embodiments, total serum IgG is reduced by at least 10%, at least 20%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, or at least 70% in a subject after a single administration of an FcRn antagonist molecule. 【0222】 In some embodiments, the clearance of total serum IgG is increased in a subject after administration of an FcRn antagonist molecule. In some embodiments, the clearance of total serum IgG in a subject after a single therapeutic administration of an FcRn antagonist molecule is equivalent to the clearance of total serum IgG in a subject after a single therapeutic administration of efgartigimod. In some embodiments, the clearance of total serum IgG in a subject after a single therapeutic administration of an FcRn antagonist molecule is similar to or the same as the clearance of total serum IgG in a subject after a single therapeutic administration of efgartigimod. 【0223】 In some embodiments, the clearance of total serum IgG in a subject after a single administration of an FcRn antagonist molecule is similar to the clearance of total serum IgG in a subject after a single administration of an equivalent amount of efgartigimod. In some embodiments, the clearance of total serum IgG in a subject after a single administration of an FcRn antagonist molecule is similar to or the same as the clearance of total serum IgG in a subject after a single administration of an equivalent amount of efgartigimod. 【0224】 In one embodiment, the FcRn antagonist molecule is administered to a subject simultaneously or sequentially with an additional therapeutic agent. In one embodiment, the additional therapeutic agent is an anti-inflammatory agent. In one embodiment, the additional therapeutic agent is a corticosteroid. In one embodiment, the additional therapeutic agent is rituximab, daclizumab, basiliximab, muromonab-CD3, infliximab, adalimumab, omalizumab, efalizumab, natalizumab, tocilizumab, eculizumab, golimumab, canakinumab, ustekinumab, or belimumab. In one embodiment, the additional therapeutic agent is a leukocyte-depleting agent. 【0225】 In one embodiment, the additional therapeutic agent is a B cell depleting agent. In one embodiment, the B cell depleting agent is an antibody. In one embodiment, the B cell depleting antibody is an antibody that specifically binds to CD10, CD19, CD20, CD21, CD22, CD23, CD24, CD37, CD53, CD70, CD72, CD74, CD75, CD77, CD79a, CD79b, CD80, CD81, CD82, CD83, CD84, CD85, or CD86. 【0226】 In some embodiments, the FcRn antagonist molecule is administered intravenously, ie, once every week, once every two weeks, once every three weeks, once every four weeks, once every month, or once every six weeks. 【0227】 In some embodiments, the FcRn antagonist molecule is administered subcutaneously, hi some embodiments, the FcRn antagonist molecule is administered subcutaneously once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every six weeks. [Example] 【0228】 The following examples are offered by way of illustration and not by way of limitation. 【0229】 Example 1 Identification of FcRn antagonist molecular variants A composition comprising a group of Fc antagonist molecules was characterized and its composition determined. Sample batch 1 was used as an analytical reference standard. All analyses were performed on batch 1 and sample batch 2, which was a working reference standard, and on sample batch 3, which was a reference standard, both of which were derived from the same drug substance batch, and were used throughout clinical development. The batches were produced using a vector designed to express SEQ ID NO:2 using the CHOK1SV GS-KO cell line (Lonza Group Ltd.). 【0230】 The charge heterogeneity of the reference sample was assessed using strong cation exchange high-performance liquid chromatography (CEX HPLC). This assay was used to determine the charge heterogeneity profile of the sample to assess purity. Proteins present in the sample were separated and quantified according to their surface charge distribution, based on the interaction of the charge on the protein's surface with the charged groups on the surface of the column. Proteins are positively charged in a buffer with a pH value below their pI. Proteins were eluted from the column using a sodium chloride gradient (mobile phase B), with acidic species eluting first, followed by more basic species. The separated components were passed through a UV detector cell, and the absorbance was measured at a wavelength of 220 nm. The results are shown in Table 5 and Figure 1. 【0231】 Eluted species peaks were classified as acidic or basic based on their elution time relative to the main peak in the CEX profile. Peaks eluting earlier than the main peak (peak 8) were identified as acidic species (peaks 1-7), and peaks eluting later (peaks 9-12) were identified as basic species. A total of 12 charged species were identified by CEX for all three reference standards. The main isoform is present at approximately 65% ​​relative percentage area. The total basic and acidic isoforms account for approximately 18% and 17% relative percentage area, respectively. Table 5: CEX results for FcRn antagonist reference standards [Table 5] 【0232】 The identities of the different CEX isoform peaks were determined by reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) analysis of the intact, trypsin-digested, isolated CEX fractions. The identities of the various peaks are presented in Figure 2 and Table 6. 【0233】 The identity of peak 9 (i.e., the single-lysine clipping variant) and peak 11 (i.e., the non-lysine clipping variant) was also confirmed by analyzing samples after treatment with carboxypeptidase B (CPB), which resulted in complete lysine cleavage. Table 6: Identities of charge variants in CEX [Table 6] - = identity could not be determined as the abundance of this peak was too low to perform fraction collection. 1 Minor sialylated variants (Fc / 0K+NANA) co-elute under peaks 4, 6, and 7. 2 The Fc fragment, double C-terminal lysine clipped, double C-terminal extended variant (Fc / 0k / +2ext), if present, also elutes under peak 6. 3 The Fc fragment, double C-terminal lysine clipped, single C-terminal extension variant (Fc / 0k / +1ext), if present, also elutes under peak 7. 4 Carboxypeptidase treatment did not result in complete reduction of peaks 9 and 11, so unknown variants may be co-eluting at this retention time. 【0234】 The charge heterogeneity of the reference sample was also assessed by imaging capillary isoelectric focusing (icIEF), and the results are shown in Table 7 and Figure 3. 【0235】 Peaks were numbered based on their measured isoelectric point (pI) relative to the main profile peak. Peaks exhibiting a pI at a lower pH than that of the main peak were identified as acidic species, and peaks exhibiting a pI at a higher pH were identified as basic species. 【0236】 Six isoforms were detected across a pI range of 6.7 to 7.6. The major isoform was detected at a pI of approximately 7.2 and a relative percentage area of ​​67%. The total basic isoform accounted for 15% of the relative percentage area, and the total acidic isoform accounted for 18% of the relative percentage area. Table 7: Results for icIEF testing of reference standards [Table 7] 【0237】 Because fractionation of separated charge variants is more difficult with icIEF compared to CEX, a different approach was used to characterize the charge variants resolved by icIEF. The CEX fractions isolated and identified above were subjected to icIEF, and isoform identification was achieved based on the electropherogram. The identities of the different isoforms are presented in Table 8. 【0238】 By subjecting the CEX fraction of peak 6 to icIEF, it can be concluded that the double deamidated variant and the double extended variant eluted in icIEF as isoform 5. Previous icIEF spiking studies with pure recombinantly produced double C-terminal extended variants also showed that the double extended variant eluted as isoform 5 in icIEF. 【0239】 The CEX fraction of peak 7 eluted as isoform 4 in icIEF, and isoform 4 was therefore identified as the co-elution of a single deamidated and single elongated variant. 【0240】 Peak 8, identified as the major variant in CEX, double lysine-clipped Fc, eluted as the major isoform 3 in icIEF. 【0241】 Isoform 2 in icIEF was identified as a single lysine clipping variant, which was confirmed by icIEF of CEX peak 9. 【0242】 Isoform 1 was identified as the non-lysine-clipped variant by icIEF of CEX peak 11. The identities of the single-lysine-clipped and non-lysine-clipped variants were also confirmed by analyzing samples after treatment with carboxypeptidase (CPB), which resulted in complete lysine cleavage. After treatment of the samples with CPB, a decrease in isoforms 1 and 2 was observed, and an unknown variant was observed eluting at the same retention time, similar to that observed for CEX. 【0243】 Compared to the CEX profile, oxidized members of the population of Fc antagonist molecules were not resolved by icIEF. This was confirmed by analyzing the CEX fractions of peak 10 (single-oxidized variant with double lysine clipping) and peak 11b (double-oxidized variant with double lysine clipping), both of which eluted as isoform 3 (previously identified as the double-lysine clipping variant) in icIEF, and by analyzing the CEX fraction of peak 11a (single-lysine clipping and single-oxidized variant), which eluted as isoform 2 (previously identified as the single-lysine clipping variant) in icIEF. This was related to the separation mechanism. In icIEF, charge variants were separated based on apparent pI. In CEX, charge variants were separated by surface charge. For Fc antagonist molecules, oxidation has an effect on surface charge, which results in resolved peaks in CEX. Table 8: Identification of charge variants by icIEF based on analysis of CEX fractions [Table 8] - = identity could not be determined as the abundance of this peak was too low to allow fraction collection and analysis in icIEF. 1 The Fc fragment, double C-terminal lysine clipped, double C-terminal extended variant (Fc / 0k / +2ext), if present, also elutes under CEX peak 6. 2 The Fc fragment, double C-terminal lysine clipped, single C-terminal extension variant (Fc / 0k / +1ext), if present, also elutes under CEX peak 7. 【0244】 Example 2 Identifying the frequency of FcRn antagonist molecular variants The frequency of N-terminal truncations was detected by RPLC-MS and reduced peptide mapping (tryptic and chymotryptic digests) of the intact, N-deglycosylated, reduced protein and quantified by CEX HPLC. The relative % peak areas for peak 4 (N-terminal DKTH loss), peak 5 (N-terminal DK loss), and peak 12 (N-terminal D loss) are shown in Table 9. 【0245】 Comparably low levels of N-terminal cleavage are observed by CEX upon release, as demonstrated by data from reference standard samples and process qualification batches in Figure 1. Table 9: Relative percentage of N-terminal truncations determined by CEX [Table 9] 【0246】 Furthermore, during the long-term stability study, no changes for peaks 4 and 5 were observed at -70°C, +5°C, and +25°C, as demonstrated in Figures 4 and 5, respectively. 【0247】 We conclude that N-terminal truncation variants are quality attributes that contribute to product heterogeneity. 【0248】 C-terminal lysine clipping can be detected by RPLC-MS and reduced peptide mapping of the intact, N-deglycosylated, reduced protein, and quantified by CEX HPLC and icIEF. In the CEX profile, the main peak 8 and basic peaks 9 and 11 corresponded to the double-lysine-clipped, single-lysine-clipped, and non-lysine-clipped variants, respectively (see Table 6). In the icIEF profile, the same isoforms appear as the main isoform (double-lysine clipping), basic isoform 2 (single-lysine clipping), and basic isoform 1 (non-lysine clipping) (see Table 8). 【0249】 As demonstrated in Tables 10 and 11, the levels of C-terminal lysine clipping variants determined by CEX and icIEF were consistent across both methods, and between reference standard samples and process qualification batches. Table 10: Relative percentage of C-terminal lysine clipping variants determined by CEX [Table 10] Table 11: Relative percentage of C-terminal lysine clipping variants determined by icIEF [Table 11] 【0250】 Furthermore, during long-term stability studies, no changes in CEX peaks 9 and 11 or icIEF isoforms 1 or 2 were observed at -70°C, +5°C, and +25°C, as shown in Figures 6-9. Therefore, we concluded that the C-terminal lysine variants are quality attributes that contribute to product heterogeneity and have no effect on potency. 【0251】 Three deamidation sites were identified in members of the population of Fc antagonist molecules during reduced tryptic peptide mapping followed by RP-LC / MS detection (see Table 15). These three identified deamidation sites are GFYPSDIAVEWESNGQPENNYK (SEQ ID NO: 24) (T19, amino acid positions 151-172), VVSVLTVLHQDWLNGK (SEQ ID NO: 25) (T08, amino acid positions 082-097), and NQVSLTCLVK (SEQ ID NO: 26) (T18, amino acid positions 141-150), all of which are not involved in FcRn binding. 【0252】 Example 3 Frequency of post-translational modifications in the Fc domain The frequency of post-translational modifications in the Fc domain of the FcRn antagonist reference samples was estimated by comparing the ion intensity of the modified peptide with that of the unmodified peptide. 【0253】 For trypsin digestion, test samples were denatured in urea and then reduced with dithiothreitol (DTT). The resulting free thiol groups were alkylated using sodium iodoacetate. The samples were then digested with trypsin, and the resulting peptides were analyzed using RPLC coupled to UV and MS detection (ESI Q-TOF). 【0254】 The measured signals were aligned to the sequence using the BioConfirm algorithm implemented in MassHunter software. The mass tolerance for aligning experimental data to the sequence was set at 20 ppm. For peptide mapping under reducing conditions, methionine and tryptophan oxidation, asparagine and glutamine deamidation, and complex N-glycans (GO, GOF, GOF, GOF, GOF, GOF, GOF, GOF) were considered as variable modifications, and cysteine ​​carbamidomethylation (sample preparation related) was considered as a fixed modification. The designated enzyme was trypsin (C-terminal cleavage at lysine or arginine), and zero to two missed cleavages were allowed. Modifications were quantified using peak areas from extracted ion chromatograms obtained with a mass accuracy of 20 ppm. Aspartic acid and isoaspartic acid-containing peptides have the same m / z but can be distinguished based on chromatographic retention time, with isoaspartic acid eluting before the aspartic acid-containing peptide. 【0255】 For chymotrypsin digestion, test samples were denatured in RapiGest and then reduced with dithiothreitol (DTT). The resulting free thiol groups were alkylated using iodoacetamide. Samples were then digested with chymotrypsin, and the resulting peptides were analyzed using RPLC coupled to UV and MS detection (ESI Q-TOF). 【0256】 The measured signals were aligned to the sequence using the BioConfirm algorithm implemented in MassHunter software. The mass tolerance for matching experimental data to the sequence was set at 20 ppm. For reduced chymotrypsin peptide mapping, N-terminal cleavage was considered as a variable modification, and cysteine ​​carbamidomethylation (sample preparation related) was considered as a fixed modification. The designated enzyme was chymotrypsin (C-terminal cleavage at tyrosine, tryptophan, and phenylalanine), with zero to two missed cleavages allowed. The peak areas from extracted ion chromatograms obtained with a mass accuracy of 20 ppm were used to quantify the modifications. 【0257】 N-terminal modification Assessment of potential processing (e.g., cleavage) occurring at the N-terminus using the current sample preparation is hindered by the fact that trypsin cleaves at K and R. Therefore, additional digests were performed using chymotrypsin, which has a different preferential cleavage site. 【0258】 Using chymotrypsin, three N-terminal variants were identified at low abundance (<1%): -D, -DK, and -DKTH. 【0259】 A -DKTH cleavage peptide (TCPPCPAPELLGGPSVFLFPPKPK (SEQ ID NO: 27), 005-028) was also identified using tryptic digests. The levels of this peptide are shown in Table 12. Similar low levels (less than 1.6%) of this peptide were found in all samples tested. Table 12: Relative quantification of N-terminal modifications. Quantification based on extracted ion MS chromatograms. [Table 12] 【0260】 C-terminal modification Table 13 presents the C-terminal peptide species present in the population of Fc antagonist molecules. The predominant C-terminal peptide was lysine (K) clipping. The level of K cleavage ranged from 88.0% to 89.0%. Lysine cleavage was similar for all reference standards. Another C-terminal variant was identified as SLSLSP (caused by C-terminal GK cleavage and P amidation) at a level of approximately 0.5%. Table 13: Relative quantification of C-terminal modifications based on extracted ion MS chromatograms [Table 13] 【0261】 Deamidation and Isomerization The identified aspartic acid (D) isomerization and asparagine (Q) deamidation sites are presented in Tables 14 and 15. 【0262】 Two peptides were found to be isomerized: peptides 055-068 and 173-189. The percentage of isomerization was relatively low (less than 1%) and comparable to that for the reference standard. 【0263】 Three peptides were found to be deamidated: peptides 082-097, 141-150, and 151-172. The level of deamidation was comparable between the reference standards and was highest for peptide 151-172. 【0264】 Table 14: Relative quantification of aspartic acid isomerization based on extracted ion MS chromatograms [Table 14] Table 15: Relative quantification of deamidation based on extracted ion MS chromatograms [Table 15] 【0265】 oxidation The identified oxidation sites are presented in Table 16. Methionine oxidation in peptides 197-213 was found for the analyzed reference samples at levels ranging from 0.7% to 1.0%. Tryptophan oxidation was not observed. 【0266】 Table 16: Relative quantification of methionine oxidation based on extracted ion MS chromatograms [Table 16] 【0267】 N-glycosylation Table 17 presents the N-glycosylation site occupancy (Asn77 in peptides 073-081). The overall site occupancy was 97.8%-97.9% across the three reference standards. The predominant glycoform was G0F (59.2%-64.3%). The different glycoforms observed are in good agreement with those observed in RPLC-MS analysis and N-linked oligosaccharide profiling. Table 17: Relative quantification of N-glycosylation based on extracted ion MS chromatograms [Table 17] 【0268】 Hydrophilic interaction liquid chromatography (HILIC) fluorescence chromatograms of 2-aminobenzamide (2-AB)-labeled N-glycans from the reference samples are shown in Figures 10 and 11. Peak identification was the result of mass spectrometry data interpretation and correlation of chromatographic elution with glycan biosynthesis rules. Quantification was based on fluorescence peak area. N-glycan identity and relative intensity are shown in Table 18, and Figure 12 shows the same data in a graphical representation. Galactosylation and fucosylation degrees are shown in Table 19. A graphical representation is shown in Figure 13. [Table 18] Table 19: Galactosylation and fucosylation degree of reference samples at the glycan level [Table 19] 【0269】 All samples had similar profiles, with G0F being the predominant glycoform, followed by G1F and G2F. Lower levels of nonfucosylated N-glycans, Man5, sialylation, and GlcNac loss were detected at comparable levels in all samples. Reference sample Batch 3 had a slightly lower degree of galactosylation compared to the other samples. The degree of fucosylation was 94.7% to 94.9% for all tested samples. 【0270】 The RPLC-UV 214 nm spectrum of the intact reference standard is shown in Figure 14. The annotated peak identities and mass accuracies, as obtained from the deconvoluted MS spectrum for each peak, are presented in Table 20. Table 20: Results for ESI-MS of intact primary reference standard batch 1 [Table 20] Da = Daltons; Fc / 0K = double lysine clipping; Fc / 1K = single lysine clipping; Fc / 2K = non-lysine clipping It may be a method-induced variant. 【0271】 The major mass detected was equivalent to the calculated major intact theoretical mass of 53,915 Da for the population of Fc antagonist molecules based on a double C-terminal lysine-clipped amino acid sequence with two G0F glycans each at 100% occupancy. Other peaks were identified as C-terminal lysine-clipped variants (single or double clipping), N-terminal DK loss, +18 Da or +36 Da additions (potentially method-induced water additions), reduced variants (lack of interchain disulfide bridges), reduced variants of on-column reoxidation, partially unglycosylated Fc, and Fc lacking disulfide bonds. 【0272】 The deconvoluted spectrum (with N-glycoform annotation) of the major peak in the RPLC profile (i.e., the double C-terminal lysine clipping variant) is shown in Figure 15. The measured molecular weight and mass accuracy for each glycoform are shown in Table 21. The relative intensity for each glycoform is shown in Table 22. A graphical representation of the relative amounts of the various N-glycans for all samples is provided in Figure 16. Table 21: Measured molecular masses and corresponding mass accuracies for glycoforms of intact reference samples [Table 21] Table 22: Relative intensities of glycoforms in intact reference samples [Table 22] 【0273】 It can be concluded from the graph that the predominant glycoform was G0F / G0F, and small differences in N-glycosylation were observed between samples. 【0274】 Example 4 Properties of pharmaceutical formulations agglomeration 【0275】 GP HPLC was performed to determine the levels of monomer and aggregate species present in the FcRn antagonist reference samples and to assess the conformation of the protein under non-denaturing conditions. The results are shown in Table 23 and Figure 17. For all three reference standards, the percentage of monomer was 99.6% and the percentage of aggregate was 0.4%. Table 23: Results for GP HPLC testing of reference standards [Table 23] LOQ=0.1%, LOD=0.04% 【0276】 Disulfide bonds As shown in Figure 18 and Table 24, under non-reducing conditions, a major peak corresponding to the molecular weight of the intact Fc region was visible in the electropherogram. The purity (% intact Fc) under non-reducing conditions was 98.2%. Several minor peaks migrating before the IgG peak were visible in the enlarged electropherograms for Primary Reference Standard Batch 1 and Working Reference Standard Batch 2, which most likely corresponded to reduced (single Fc domain) fragments. Table 24: Results for non-reduced CE SDS testing of reference standards [Table 24] 【0277】 Mass and mass heterogeneity SEC-MALS was performed to further confirm the molecular mass distribution and relative amounts of the monomeric and aggregate species observed by the GP HPLC method coupled with UV detection. The ability of the separated components to scatter light, measured using a light scattering detector, was used to estimate the molecular mass. 【0278】 The monomeric molecular mass for the reference standard, determined by size exclusion chromatography multi-angle light scattering (SEC-MALS), was equivalent to the theoretical molecular mass of 53,915 Da, consistent with the results obtained by GP HPLC (see Table 25 and Figure 18). Table 25: Results for monomer mass heterogeneity analysis of reference standards [Table 25] ND: Not detected 【0279】 Free thiols The free thiol content of the reference standards was determined using Ellman's reagent, and an assay was performed after denaturation of the antibody to determine the presence of any free cysteine ​​residues within the internal structure of the protein. 【0280】 Under native conditions, free thiol levels were below the calculated limit of quantitation (LOQ) of the method (Table 26). Under denaturing conditions, slightly higher free thiol levels were detected for Primary Reference Standard Batch 1 / Working Reference Standard Batch 2 compared to Reference Standard Batch 3. However, these levels of free thiol were considered low and close to the LOQ of the method. Table 26: Free thiol assay results for reference samples [Table 26] 【0281】 Example 5 Batch variability of compositions containing FcRn antagonist molecular variants As in Example 1, compositions containing a population of Fc antagonist molecules were characterized to determine their composition. 【0282】 The charge heterogeneity of the samples was evaluated using strong cation exchange high-performance liquid chromatography (CEX HPLC). Proteins present in the samples were separated and quantified according to their surface charge distribution, based on the interaction of the charge on the protein's surface with the charged groups on the surface of the column. Proteins are positively charged in a buffer with a pH value below their pI. Proteins were eluted from the column using a sodium chloride gradient (mobile phase B), with acidic species eluting first, followed by more basic species. The separated components were passed through a UV detector cell, and the absorbance was measured at a wavelength of 220 nm. The results are shown in Tables 26 and 27. 【0283】 Eluted species peaks were classified as acidic or basic based on their elution time relative to the main peak in the CEX profile. Peaks eluting earlier than the main peak (peak 8) were identified as acidic species (peaks 1-7), and peaks eluting later (peaks 9-12) were identified as basic species. A total of 12 charged species were identified by CEX for all tested samples. Consistent with the results in Example 1, the main isoform is present at approximately 64% relative percentage area. Total basic and acidic isoforms account for approximately 16% and 19% relative percentage area, respectively. The identities of the different CEX isoform peaks are presented in Figure 2 and Table 6. 【0284】 The charge heterogeneity of the samples was also assessed by imaging capillary isoelectric focusing (icIEF). The results are shown in Tables 27 and 28. 【0285】 As in Example 1, peaks were numbered based on their measured isoelectric point (pI) relative to the main profile peak. Peaks exhibiting a pI at a lower pH than that of the main peak were identified as acidic species, and peaks exhibiting a pI at a higher pH were identified as basic species. 【0286】 Six isoforms were detected across a pI range of 6.7 to 7.6. The major isoform was detected at a pI of approximately 7.2 and a relative percentage area of ​​approximately 65%. The total basic isoform accounted for approximately 16% of the relative percentage area, and the total acidic isoform accounted for approximately 18% of the relative percentage area. The identities of the different isoforms are presented in Table 8. [Table 27] [Table 28] 【0287】 Batch variations in N-glycan morphology within the FcRn antagonist compositions were also analyzed. Hydrophilic interaction liquid chromatography (HILIC) fluorescence chromatograms of 2-aminobenzamide (2-AB)-labeled N-glycans from the samples were analyzed as described in Example 3. Peak identification was the result of mass spectrometry data interpretation and correlation of chromatographic elution with glycan biosynthesis rules. Quantification was based on fluorescence peak area. The N-glycan identities and relative intensities of the samples are shown in Tables 29-35. [Table 29] [Table 30] [Table 31] [Table 32] [Table 33] [Table 34] [Table 35] *** 【0288】 The present invention is not limited in scope by the specific embodiments described herein. Indeed, various modifications of the invention in addition to those described will become apparent to those skilled in the art from the foregoing description and accompanying figures. Such modifications are intended to be within the scope of the appended claims.

Claims

[Claim 1] A composition comprising a group of FcRn antagonist molecules, wherein at least a portion of the FcRn antagonist molecules in the group consists of a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, and the amino acid sequence of the first and second Fc domains is sequence number 1, provided that the group is not a homogeneous group of homodimeric FcRn antagonist molecules in which the amino acid sequences of both the first and second Fc domains consist of sequence numbers 2, 3, 20, or 21. [Claim 2] The composition according to claim 1, wherein each FcRn antagonist molecule in the group consists of a variant Fc region comprising a dimer of a first Fc domain and a second Fc domain, and the amino acid sequence of the first and second Fc domains is such that it corresponds to Sequence ID No.

1. [Claim 3] The amino acid sequences of the first and second Fc domains are, (i) Each consists of sequence number 3 and sequence number 12, (ii) Each consists of sequence number 3 and sequence number 9, (iii) Each consists of sequence number 2 and sequence number 3, (iv) Each consists of sequence number 3 and sequence number 6, or (v) The composition according to claim 1, each comprising any one of sequence numbers 2 to 22 and any one of sequence numbers 2 to 22. [Claim 4] The composition according to claim 1, wherein the amino acid sequences of both the first and second Fc domains consist of any one of SEQ ID NOs. 5, SEQ ID NOs. 6, SEQ ID NOs. 7, SEQ ID NOs. 8, SEQ ID NOs. 9, SEQ ID NOs. 10, SEQ ID NOs. 11, SEQ ID NOs. 12, SEQ ID NOs. 13, SEQ ID NOs. 14, SEQ ID NOs. 15, SEQ ID NOs. 16, SEQ ID NOs. 17, SEQ ID NOs. 18, SEQ ID NOs. 19, or SEQ ID NOs.

22. [Claim 5] The population comprises: (a) a first subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of both the first and second Fc domains of the FcRn antagonist molecules in the first subpopulation are the same as SEQ ID NO: 3; and (b) at least one of the following: (i) A second subgroup of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the second subgroup consist of SEQ ID NO: 3 and SEQ ID NO: 12, respectively. (ii) A third subgroup of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the third subgroup consist of SEQ ID NO: 3 and SEQ ID NO: 9, respectively. (iii) A fourth subgroup of FcRn antagonist molecules, wherein the amino acid sequences of both the first and second Fc domains of the FcRn antagonist molecules in the fourth subgroup consist of SEQ ID NO: 3, and two asparagine residues in each FcRn antagonist molecule in the fourth subgroup are deaminated. (iv) A fifth subgroup of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the fifth subgroup consist of SEQ ID NO: 3 and SEQ ID NO: 9, respectively, and one asparagine residue in each FcRn antagonist molecule in the fifth subgroup is deaminated. (v) A sixth subgroup of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the sixth subgroup consist of SEQ ID NO: 2 and SEQ ID NO: 3, respectively. (vi) A seventh subgroup of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the seventh subgroup consist of SEQ ID NO: 2 and SEQ ID NO: 3, respectively, and one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the seventh subgroup is oxidized, (vii) An eighth subgroup of FcRn antagonist molecules, wherein the amino acid sequences of both the first and second Fc domains of the FcRn antagonist molecule in the eighth subgroup are the same as SEQ ID NO: 2, (viiii) A ninth subgroup of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the ninth subgroup consist of SEQ ID NO: 3 and SEQ ID NO: 6, respectively. (ix) A tenth subgroup of FcRn antagonist molecules, wherein the amino acid sequences of the first and second Fc domains of the FcRn antagonist molecules in the tenth subgroup consist of SEQ ID NO: 2 and SEQ ID NO: 3, respectively, and one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the tenth subgroup is oxidized, and The composition according to claim 1, comprising (x) an eleventh subgroup of FcRn antagonist molecules, wherein the amino acid sequences of both the first and second Fc domains of the FcRn antagonist molecules in the eleventh subgroup consist of SEQ ID NO: 3, and two amino acid residues, independently selected from a methionine residue and tryptophan, in each FcRn antagonist molecule in the eleventh subgroup are oxidized. [Claim 6] The aforementioned group, (i) containing two, three, four, five, six, seven, eight, nine, ten, or all of the subgroups described in (b), (ii) Including the subgroups of 7, 9, or 11 above, or (iii) The composition according to claim 5, comprising the subgroups 7, 9, and 11. [Claim 7] (i) The first subgroup comprises at least 55% of the group, and / or (ii) The second subgroup is 2.5% or less of the group, and / or (iii) The third subgroup is 2.5% or less of the group, and / or (iv) The fourth subgroup is 4% or less of the group, and / or (v) The fifth subgroup is 10% or less of the group, and / or (vi) The sixth subgroup is 20% or less of the group, and / or (vii) The seventh subgroup is 6% or less of the group, and / or (viiii) The eighth subgroup is 8% or less of the group, and / or (ix) The ninth subgroup is 3.5% or less of the group, and / or (x) The 10th subgroup is 1% or less of the group, and / or (xi) The composition according to claim 5, wherein the 11th subgroup is 1% or less of the group. [Claim 8] (i) At least 97% of the Fc domains in the population contain an N-glycan at EU position 297, and / or (ii) At least 50% of the Fc domains in the population contain G0F N-glycan at EU position 297, and / or (iii) At least 20% of the Fc domains in the population contain G1F N-glycan at EU position 297, and / or (iv) At least 5% of the Fc domains in the population contain G2F N-glycan at EU position 297, and / or (v) The composition according to claim 1, wherein at least 2% of the Fc domains in the population contain G0 N-glycan at EU position 297. [Claim 9] (i) At least 40% of the population comprises a first Fc domain containing G0F N-glycan at EU position 297, and / or a second Fc domain containing G0F N-glycan at EU position 297. (ii) At least 20% of the population comprises a first Fc domain containing G0F N-glycan at EU position 297, and / or a second Fc domain containing G1F N-glycan at EU position 297. (iii) At least 10% of the population contains either a first Fc domain containing G1F N-glycan at EU position 297 and a second Fc domain containing G1F N-glycan at EU position 297, or a first Fc domain containing G0F N-glycan at EU position 297 and a second Fc domain containing G2F N-glycan at EU position 297, and / or (iv) At least 5% of the population comprises a first Fc domain containing G1F N-glycan at EU position 297, and a second Fc domain containing G2F N-glycan at EU position 297, and / or (v) At least 2% of the population comprises a first Fc domain containing G2F N-glycan at EU position 297, and / or a second Fc domain containing G2F N-glycan at EU position 297. (vi) The composition according to claim 1, wherein at least 4% of the population comprises a first Fc domain containing G0F N-glycan at EU position 297 and a second Fc domain containing G0 N-glycan at EU position 297. [Claim 10] (i) At least 95% of the Fc domains in the population have aspartic acid, lysine, threonine, histidine, threonine, and cysteine ​​at EU positions 221, 222, 223, 224, 225, and 226, and / or (ii) Less than 1% of the Fc domains in the population lack an amino acid at EU position 221 and have lysine, threonine, histidine, threonine, and cysteine ​​at EU positions 222, 223, 224, 225, and 226, and / or (iii) Less than 1% of the Fc domains in the population lack amino acids at EU positions 221 and 222, and have threonine, histidine, threonine, and cysteine ​​at EU positions 223, 224, 225, and 226, and / or (iv) 2% or less of the Fc domains in the population lack an amino acid at EU positions 221-224, and have threonine and cysteine ​​at EU positions 225 and 226, and / or (v) The composition according to claim 1, wherein 1% or less of the Fc domains in the population lack amino acids at EU positions 221, 222, 223, 224, 225, and 226. [Claim 11] (i) Less than 1% of the Fc domains in the population have aspartic acid isomerization at EU position 280 or 401, and / or (ii) Less than 10% of the Fc domains in the population have asparagine deamidation at EU position 384, 389, or 390, and / or (iii) 3% or less of the Fc domains in the population have asparagine deamidation at EU position 315, and / or (iv) 3% or less of the Fc domains in the population have asparagine deamidation at EU position 361, and / or (v) Less than 1% of the Fc domains in the population have asparagine deamidation at EU position 276 or 286, and / or (vi) 5% or less of the Fc domains in the population have methionine oxidation at EU position 428, and / or (vii) Less than 1% of the Fc domains in the population have proline amidation at EU position 445, and / or (viiii) The composition according to claim 1, wherein 1% or less of the Fc domains in the population have tryptophan oxidation at EU position 277. [Claim 12] (i) 0.5% or less of the FcRn antagonist molecules in the population are aggregated, and / or (ii) At least 95% of the dimers in the group are linked by at least one disulfide bond, and / or (iii) The average molecular weight of the unaggregated FcRn antagonist molecules in the population is 54 to 56 kDa, and / or (iv) The composition according to claim 1, wherein the percentage of free thiol groups in the group is 1% or less. [Claim 13] (i) At least 35% of the Fc domains in the population contain galactose, and / or (ii) At least 90% of the Fc domains in the population contain fucose, and / or (iii) The composition according to any one of claims 1 to 12, wherein at least 1.5% of the Fc domains in the population contains sialic acid. [Claim 14] It is an aqueous solution, (i) a composition comprising approximately 25 mM sodium phosphate, approximately 100 mM sodium chloride, approximately 150 mM L-arginine, and approximately 0.02% (w / v) polysorbate 80, wherein the composition has a pH of approximately 6.7 and optionally contains 20 mg / ml of the FcRn antagonist molecule population, (ii) A composition comprising approximately 4 mM sodium phosphate, approximately 146 mM sodium chloride, approximately 24 mM L-arginine, and approximately 0.0032% (w / v) polysorbate 80, wherein the composition has a pH of approximately 6.7 and optionally contains approximately 3.2 mg / ml of the FcRn antagonist molecule population. (iii) comprising about 20 mM L-histidine, about 100 mM sodium chloride, about 60 mM sucrose, about 10 mM L-methionine, and about 0.04% (w / v) polysorbate 20, wherein the composition has a pH of about 6.0 and optionally contains about 180 mg / ml of the FcRn antagonist molecules, or The composition according to claim 1, comprising (iv) about 20 mM L-histidine, about 50 mM L-arginine, about 100 mM sodium chloride, about 60 mM sucrose, about 10 mM L-methionine, and about 0.04% (w / v) polysorbate 80, wherein the composition has a pH of about 6.0 and optionally comprises about 200 mg / ml of the FcRn antagonist molecule population. [Claim 15] A pharmaceutical composition comprising the composition described in any one of claims 1 to 14. [Claim 16] The pharmaceutical composition according to claim 15, for use in reducing the level of serum IgG autoantibodies in a subject. [Claim 17] The pharmaceutical composition according to claim 15 for use in the treatment of autoimmune diseases.

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