Subcutaneous formulations, pre-filled syringes and methods of use thereof

Abstract

Provided herein are pharmaceutical compositions comprising an FcRn antagonist (e.g., efgartigimod, or a biosimilar version thereof) in a pre-fdled syringe for subcutaneous administration and methods of use thereof for reducing the serum IgG level of a subject in need thereof (e.g., a subject having an autoimmune disease such as generalized myasthenia gravis (gMG)).

Description

SUBCUTANEOUS FORMULATIONS, PRE-FILLED SYRINGES AND METHODS OF USE THEREOF CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional PatentApplication No.63 / 645,466, filed May 10, 2024, the entire contents of which are hereby incorporated by reference in its entirety. FIELD

[0002] The present disclosure relates to subcutaneous pharmaceutical compositions (e.g.,formulations) and approved products comprising an FcRn antagonist (e.g., efgartigimod, or a biosimilar version thereof) and methods of use thereof including methods of administering these formulations with a pre-filled syringe. BACKGROUND

[0003] VYVGART® (efgartigimod alfa-fcab) is a neonatal Fc receptor (FcRn) antagonistthat, as of April 2024, is indicated for the treatment of gMG in adult patients who are anti- acetylcholine receptor (AChR) antibody positive. VYVGART was first approved with a first label in the United States by the Food and Drug Administration (FDA) in 2021 on the basis of clinical trial data from the ADAPT study (NCT03669588). VYVGART was subsequently approved for the treatment of gMG in Japan, Europe, United Kingdom, Israel, China, and Canada during 2022-2023.

[0004] A subcutaneous dosage form of VYVGART® (VVYGART® HYTRULO), asinitially approved, was described as a sterile, preservative free, yellowish, clear to slightly opalescent solution supplied in a single-dose vial for subcutaneous injection. Each 5.6 mL single-dose vial contained 1,008 mg of efgartigimod alfa at a concentration of 180 mg / mL and 11,200 Units of human recombinant hyaluronidase at a concentration of 2000 U / mL. In addition, each mL of solution contained L-histidine (1.4 mg), L-histidine hydrochloride monohydrate (2.2 mg), L-methionine (1.5 mg), polysorbate 20 (0.4 mg), sodium chloride (5.8 mg), sucrose (20.5 mg), and water for injection, USP, at a pH of 6.0.

[0005] As shown in International Application No. PCT / EP2020 / 065716, incorporated byreference herein in its entirety, when subcutaneous formulations were made with a concentration of efgartigimod of 200 mg / mL, reversible solid-liquid phase transition was observed when the 1 BUSINESS.32923153.1formulation was agitated for 5 days at 5 ˚C. There is a need in the art for high concentration subcutaneous formulations particularly for use in pre-filled syringes for self-administration by patients. SUMMARY

[0006] The instant disclosure is directed to pharmaceutical compositions and approvedproducts comprising an FcRn antagonist (e.g., efgartigimod, or a biosimilar version thereof) and methods of use thereof for reducing the serum IgG level of a subject in need thereof (e.g., a subject having an autoimmune disease such as gMG).

[0007] In order to enhance manufacturing and improve ease of subcutaneous administration,a new optimized second-generation subcutaneous drug product (Efgartigimod SC Gen2) was developed as disclosed and claimed herein. Specifically, provided herein are pharmaceutical compositions of efgartigimod and a hyaluronidase, or a biosimilar version thereof in solution for subcutaneous injection.

[0008] Provided herein are approved products comprising: efgartigimod and a hyaluronidase,or a biosimilar version thereof in solution for injection.

[0009] Also provided herein are biological products comprising efgartigimod and ahyaluronidase in a solution for subcutaneous injection, wherein the biological product is packaged in a pre-filled syringe. In some embodiments, the package includes instructions for administration of the subcutaneous drug product. In some embodiments, the instructions are for self-administration by the subject. In some embodiments, the package includes a label that identifies the biological product as indicated for the treatment of gMG.

[0010] Kits comprising the disclosed approved products or biological products are alsoprovided.

[0011] Provided herein are methods for treating gMG in a patient, the methods comprisingadministering the disclosed approved products to the patient in an amount and manner that is described in a label for the approved product.

[0012] Provided herein are methods of offering for sale an approved product, said methodscomprising offering for sale such approved product, wherein an approved product label for a reference product for such approved product includes instructions for treating adult patients.

[0013] Also provided herein is a pre-filled syringe containing a liquid pharmaceuticalformulation comprising a human neonatal Fc receptor (FcRn) antagonist and a hyaluronidase, 2 BUSINESS.32923153.1wherein the FcRn antagonist comprises or consists of a variant IgG Fc region, or FcRn-binding fragment thereof, wherein the variant IgG Fc region, or FcRn-binding fragment thereof, comprises or consists of a first Fc domain and a second Fc domain which form a homodimer or a heterodimer, and wherein the first Fc domain and the second Fc domain each comprise amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436. In some embodiments, the first Fc domain and / or the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4. In some embodiments, the first Fc domain and the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4. In some embodiments, the first Fc domain and the second Fc domain comprise or consist of the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the first Fc domain and the second Fc domain comprise or consist of the amino acid sequence set forth in SEQ ID NO: 2. In some embodiments, the first Fc domain and the second Fc domain comprise or consist of the amino acid sequence set forth in SEQ ID NO: 3. In some embodiments, the first Fc domain and the second Fc domain comprise or consist of the amino acid sequence set forth in SEQ ID NO: 4.

[0014] In some embodiments, the FcRn antagonist is a population of FcRn antagonistmolecules, wherein each FcRn antagonist molecule in the population consists of a dimer of a first Fc domain and a second Fc domain, and wherein the population comprises a first subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of both the first and the second Fc domains of the FcRn antagonist molecules in the first subpopulation consist of the amino acid sequence set forth in SEQ ID NO: 3; and at least one of: a second subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and the second Fc domains of the FcRn antagonist molecules in the second subpopulation consist of the amino acid sequences set forth in SEQ ID NO: 3 and SEQ ID NO: 13, respectively; a third subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and the second Fc domains of the FcRn antagonist molecules in the third subpopulation consist of the amino acid sequences set forth in SEQ ID NO: 3 and SEQ ID NO: 10, respectively; a fourth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of both the first and the second Fc domains of the FcRn antagonist molecules in the fourth subpopulation consist of the amino acid sequence set forth in SEQ ID NO: 3, and wherein two asparagine residues in each FcRn antagonist molecule in the fourth subpopulation are deaminated; a fifth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and the second Fc domains of the FcRn antagonist molecules in the fifth subpopulation consist of the 3 BUSINESS.32923153.1amino acid sequence set forth in SEQ ID NO: 3, and wherein one asparagine residue in each FcRn antagonist molecule in the fifth subpopulation is deaminated; a sixth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and the second Fc domains of the FcRn antagonist molecules in the sixth subpopulation consist of the amino acid sequences set forth in 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 the second Fc domains of the FcRn antagonist molecules in the seventh subpopulation consist of the amino acid sequence set forth in SEQ ID NO: 3, and wherein 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 the second Fc domains of the FcRn antagonist molecules in the eighth subpopulation consist of the amino acid sequence set forth in SEQ ID NO: 2; a ninth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and the second Fc domains of the FcRn antagonist molecules in the ninth subpopulation consist of the amino acid sequences set forth in SEQ ID NO: 3 and SEQ ID NO: 7, respectively; a tenth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and the second Fc domains of the FcRn antagonist molecules in the tenth subpopulation consist of the amino acid sequences set forth in SEQ ID NO: 2 and SEQ ID NO: 3, respectively, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the tenth subpopulation is oxidized; and an eleventh subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of both the first and the second Fc domains of the FcRn antagonist molecules in the eleventh subpopulation consist of the amino acid sequence set forth in SEQ ID NO: 3, and wherein two amino acid residues, independently selected from a methionine residue and a tryptophan residue, in each FcRn antagonist molecule in the eleventh subpopulation is oxidized.

[0015] In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar versionthereof. In some embodiments, the hyaluronidase comprises recombinant human PH20 (rHuPH20). In some embodiments, the liquid pharmaceutical formulation comprises 160-240 mg / mL, optionally 180-220 mg / mL, optionally 190-210 mg / mL of efgartigimod, or optionally about 200 mg / mL of efgartigimod. In some embodiments, the liquid pharmaceutical formulation comprises 200 mg / mL of efgartigimod. In some embodiments, the liquid pharmaceutical formulation comprises 1,400-2,800, optionally 1,600-2,600, optionally 1,800-2,400 Units / mL of the hyaluronidase, or optionally about 2,000 Units / mL of the hyaluronidase. In some embodiments, the liquid pharmaceutical formulation comprises 2,000 Units / mL of the hyaluronidase. In some embodiments, the liquid pharmaceutical 4 BUSINESS.32923153.1formulation comprises about 2,000 Units / mL of rHuPH20. In some embodiments, the liquid pharmaceutical formulation comprises 2,000 Units / mL of rHuPH20.

[0016] In some embodiments, the liquid pharmaceutical formulation comprises 4.2-6.2 mL,optionally 4.5-6.9 mL, optionally 4.7-6.2 mL, or optionally about 5.2 mL of liquid. In some embodiments, the liquid pharmaceutical formulation has a volume of 5.2 mL of liquid. In some embodiments, the pre-filled syringe comprises an extractable volume of the liquid pharmaceutical formulation of 4-6 mL, optionally 4.3-6.7 mL, optionally 4.5-6.0 mL, or optionally about 5.0 mL of liquid. In some embodiments, the extractable volume of the liquid pharmaceutical formulation is 5.0 mL of liquid. In some embodiments, the liquid pharmaceutical formulation has an osmolality of 350- 380 mOsm / kg H2O. In some embodiments, the liquid pharmaceutical formulation has a viscosity of between 8 and 14 mPa s at room temperature.

[0017] In some embodiments, the liquid pharmaceutical formulation comprises about 10.5mg / mL L-arginine hydrochloride, about 1.4 mg / mL L-histidine, about 2.2 mg / mL L-histidine hydrochloride monohydrate, about 1.5 mg / mL L-methionine, about 0.4 mg / mL polysorbate 80, about 4.1 mg / mL sodium chloride, and about 20.5 mg / mL sucrose, at about pH 6.0.

[0018] In some embodiments, the liquid pharmaceutical formulation comprises about 50 mML-arginine, about 20 mM L-histidine, about 10 mM L-methionine, about 0.04% polysorbate 80, about 70 mM sodium chloride, and about 60 mM sucrose.

[0019] In some embodiments, the liquid pharmaceutical formulation comprises about 50 mML-arginine hydrochloride, about 20 mM L-histidine and L-histidine hydrochloride monohydrate, about 10 mM L-methionine, about 0.04% polysorbate 80, about 70 mM sodium chloride, and about 60 mM sucrose.

[0020] In some embodiments, the liquid pharmaceutical formulation comprises 10.5 mg / mLL-arginine hydrochloride, 1.4 mg / mL L-histidine, 2.2 mg / mL L-histidine hydrochloride monohydrate, 1.5 mg / mL L-methionine, 0.4 mg / mL polysorbate 80, 4.1 mg / mL sodium chloride, and 20.5 mg / mL sucrose, at pH 6.0.

[0021] In some embodiments, the liquid pharmaceutical formulation comprises 50 mM L-arginine, 20 mM L-histidine, 10 mM L-methionine, 0.04% polysorbate 80, 70 mM sodium chloride, and 60 mM sucrose.

[0022] In some embodiments, the liquid pharmaceutical formulation comprises 50 mM L-arginine hydrochloride, 20 mM L-histidine and L-histidine hydrochloride monohydrate, 10 mM L- methionine, 0.04% polysorbate 80, 70 mM sodium chloride, and 60 mM sucrose. 5 BUSINESS.32923153.1

[0023] In some embodiments, the liquid pharmaceutical formulation comprises about 200mg / mL efgartigimod, about 2,000 U / mL rHuPH20, about 10.5 mg / mL L-arginine hydrochloride, about 1.4 mg / mL L-histidine, about 2.2 mg / mL L-histidine hydrochloride monohydrate, about 1.5 mg / mL L-methionine, about 0.4 mg / mL polysorbate 80, about 4.1 mg / mL sodium chloride, and about 20.5 mg / mL sucrose, at about pH 6.0.

[0024] In some embodiments, the liquid pharmaceutical formulation comprises about 200mg / mL efgartigimod, about 2,000 U / mL rHuPH20, about 50 mM L-arginine, about 20 mM L- histidine, about 10 mM L-methionine, about 0.04% polysorbate 80, about 70 mM sodium chloride, and about 60 mM sucrose.

[0025] In some embodiments, the liquid pharmaceutical formulation comprises about 200mg / mL efgartigimod, about 2,000 U / mL rHuPH20, about 50 mM L-arginine hydrochloride, about 20 mM L-histidine and L-histidine hydrochloride monohydrate, about 10 mM L-methionine, about 0.04% polysorbate 80, about 70 mM sodium chloride, and about 60 mM sucrose.

[0026] In some embodiments, the liquid pharmaceutical formulation comprises 200 mg / mLefgartigimod, 2,000 U / mL rHuPH20, 10.5 mg / mL L-arginine hydrochloride, 1.4 mg / mL L-histidine, 2.2 mg / mL L-histidine hydrochloride monohydrate, 1.5 mg / mL L-L-methionine, 0.4 mg / mL polysorbate 80, 4.1 mg / mL sodium chloride, and 20.5 mg / mL sucrose, at pH 6.0.

[0027] In some embodiments, the liquid pharmaceutical formulation comprises 200 mg / mLefgartigimod, 2,000 U / mL rHuPH20, 50 mM L-arginine, 20 mM L-histidine, 10 mM L-methionine, 0.04% polysorbate 80, 70 mM sodium chloride, and 60 mM sucrose.

[0028] In some embodiments, the liquid pharmaceutical formulation comprises 200 mg / mLefgartigimod, 2,000 U / mL rHuPH20, 50 mM L-arginine hydrochloride, 20 mM L-histidine and L- histidine hydrochloride monohydrate, 10 mM L-methionine, 0.04% polysorbate 80, 70 mM sodium chloride, and 60 mM sucrose.

[0029] In some embodiments, the pre-filled syringe comprises a syringe body having a barrelwith an interior volume, a distal end, and a proximal end; a plunger disposed within the interior volume of the barrel; and a nozzle at the distal end of the syringe body, wherein the FcRn antagonist and the hyaluronidase are disposed within the interior volume of the barrel between the plunger and the nozzle.

[0030] In some embodiments, the pre-filled syringe comprises an extractable volume definedas a portion of the interior volume between the plunger and the nozzle, the extractable volume being 6 BUSINESS.32923153.14.0-6.0 mL, optionally 4.3-5.7 mL, optionally 4.5-5.5 mL, or optionally about 5.0 mL. In some embodiments, the extractable volume is 5.0 mL.

[0031] In some embodiments, the nozzle has an interior volume of 0.1 to 0.3 mL. In someembodiments, the nozzle has an interior volume of about 0.2 mL. In some embodiments, the plunger comprises a stopper and a thumb pad. In some embodiments, the syringe body comprises a finger flange at its proximal end. In some embodiments, the pre-filled syringe comprises a collar positioned around the nozzle and a syringe cap removably attached to the distal end of the collar. In some embodiments, the syringe cap is attached to the distal end of the collar via a frangible connection.

[0032] In some embodiments, the syringe body is made of a transparent or translucentmaterial. In some embodiments, the liquid pharmaceutical formulation is stored in a sterile condition within the syringe body. In some embodiments, the pre-filled syringe further comprises a needle attached at the collar.

[0033] In some embodiments, the barrel interior volume and plunger are configured to expelat 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 liquid pharmaceutical formulation in the barrel in no more than 30 seconds, optionally no more than 28 seconds, optionally no more than 25 seconds, optionally no more than 20 seconds, optionally no more than 15 seconds, or optionally no more than 10 seconds, at room temperature. In some embodiments, the barrel interior volume and plunger are configured to expel 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 liquid pharmaceutical formulation in the barrel in 10seconds or greater, optionally in 15 seconds or greater, optionally 18 seconds or greater, or optionally20 seconds or greater, at room temperature. In some embodiments, the barrel interior volume and plunger are configured to expel at least 95% of the liquid pharmaceutical formulation in the barrel in between 20 to 30, 20 to 28, or 20-25 seconds, at room temperature.

[0034] In some embodiments, the pre-filled syringe is an auto-injector. In some embodiments,the auto-injector comprises a luer fit needle. In some embodiments, the auto-injector is button activated. In some embodiments, the auto-injector comprises post-delivery sharps protection.

[0035] In some embodiments, administration of the liquid pharmaceutical formulation withthe pre-filled syringe is bioequivalent to administration of the liquid pharmaceutical formulation with a syringe filled with the liquid pharmaceutical formulation at the time of injection.

[0036] Also provided herein is a kit comprising one or more of the pre-filled syringesdescribed herein in one or more containers. In some embodiments, each pre-filled syringe is in a 7 BUSINESS.32923153.1separate sealed wrapper. In some embodiments, the separate sealed wrapper is sterile. In some embodiments, the container comprises 2-10 pre-filled syringes. In some embodiments, the kit further comprises instructions for use of the one or more pre-filled syringes.

[0037] In some embodiments, the kit further comprises a needle attachable to the pre-filledsyringe. In some embodiments, the needle is 25G. In some embodiments, the needle is 5 / 8” in length. In some embodiments, the needle further comprises a needle cap. In some embodiments, the needle cap is transparent or translucent. In some embodiments, the kit further comprises a needle shield. In some embodiments, the needle is in a needle sealed wrapper, and the pre-filled syringe is in a syringe sealed wrapper. In some embodiments, the sealed wrappers are sterile.

[0038] Also provided herein are methods of administering a liquid pharmaceuticalformulation comprising an FcRn antagonist and hyaluronidase to a subject comprising placing the pre-filled syringe as described herein at room temperature until a viscosity of the liquid pharmaceutical formulation is between 8 and 14 mPa s; attaching a needle to the pre-filled syringe; pinching a site on the abdomen of the subject; inserting the needle into the pinched site; injecting the FcRn antagonist and the hyaluronidase into the subject; and removing the needle from the pinched site, thereby administering the liquid pharmaceutical formulation comprising the FcRn antagonist and the hyaluronidase to the subject.

[0039] Also provided herein are methods of administering a liquid pharmaceuticalformulation comprising an FcRn antagonist and hyaluronidase to a subject comprising placing the pre-filled syringe as described herein at room temperature for at least 30 minutes; attaching a needle to the pre-filled syringe; pinching a site on the abdomen of the subject; inserting the needle into the pinched site; injecting the FcRn antagonist and the hyaluronidase into the subject; and removing the needle from the pinched site, thereby administering the liquid pharmaceutical formulation comprising the FcRn antagonist and the hyaluronidase to the subject.

[0040] Also provided herein are methods of administering a liquid pharmaceuticalformulation comprising an FcRn antagonist and hyaluronidase to a subject comprising placing the pre-filled syringe as described herein at room temperature until a viscosity of the liquid pharmaceutical formulation is between 8 and 14 mPa s attaching a needle to the pre-filled syringe; pinching a site on the abdomen of the subject; inserting the needle into the pinched site; pushing the plunger; and removing the needle from the pinched site, thereby administering the liquid pharmaceutical formulation comprising the FcRn antagonist and the hyaluronidase to the subject. 8 BUSINESS.32923153.1

[0041] Also provided herein are methods of administering a liquid pharmaceuticalformulation comprising an FcRn antagonist and hyaluronidase to a subject comprising placing the pre-filled syringe as described herein at room temperature for at least 30 minutes; attaching a needle to the pre-filled syringe; pinching a site on the abdomen of the subject; inserting the needle into the pinched site; pushing the plunger; and removing the needle from the pinched site, thereby administering the liquid pharmaceutical formulation comprising the FcRn antagonist and the hyaluronidase to the subject.

[0042] Also provided herein are methods of administering a liquid pharmaceuticalformulation comprising an FcRn antagonist and hyaluronidase to a subject comprising placing one or more of the pre-filled syringes from the kits as described herein at room temperature until a viscosity of the liquid pharmaceutical formulation is between 8 and 14 mPa s; attaching a needle to the pre- filled syringe; pinching a site on the abdomen of the subject; inserting the needle into the pinched site; pushing the plunger; and removing the needle from the pinched site, thereby administering the liquid pharmaceutical formulation comprising the FcRn antagonist and the hyaluronidase to the subject.

[0043] Also provided herein are methods of administering a liquid pharmaceuticalformulation comprising an FcRn antagonist and hyaluronidase to a subject comprising placing one or more of the pre-filled syringes from the kits as described herein at room temperature for at least 30 minutes; attaching a needle to the pre-filled syringe; pinching a site on the abdomen of the subject; inserting the needle into the pinched site; pushing the plunger; and removing the needle from the pinched site, thereby administering the liquid pharmaceutical formulation comprising the FcRn antagonist and the hyaluronidase to the subject.

[0044] In some embodiments of the methods provided herein, the pre-filled syringe is placedat room temperature for at least 30 minutes. In some embodiments of the methods provided herein, the pre-filled syringe is placed at room temperature for 30-60 minutes. In some embodiments of the methods provided herein, the pre-filled syringe is removed from the container and placed at room temperature for 30-60 minutes.

[0045] In some embodiments of the methods provided herein, the site on the abdomen is onthe belly of the subject. In some embodiments of the methods provided herein, the site on the abdomen is at least two or three inches away from the navel of the subject. In some embodiments of the methods provided herein, the method further comprises cleaning the site on the abdomen of the subject. In some embodiments of the methods provided herein, the cleaning is done with an alcohol swab. 9 BUSINESS.32923153.1

[0046] In some embodiments of the methods provided herein, the needle is attached to thecollar. In some embodiments of the methods provided herein, the method further comprises removing the needle cap from the needle after it is attached to the pre-filled syringe. In some embodiments of the methods provided herein, the needle is inserted into the pinched site at a 45˚-90˚ angle. In some embodiments of the methods provided herein, the plunger is pushed until it stops. In some embodiments of the methods provided herein, the plunger is pushed slowly.

[0047] In some embodiments of the methods provided herein, the plunger is pushed for nomore than 30 seconds, optionally no more than 28 seconds, optionally no more than 25 seconds, optionally no more than 20 seconds, optionally no more than 15 seconds, or optionally no more than 10 seconds, at room temperature. In some embodiments of the methods provided herein, the plunger is pushed for 10 seconds or greater, optionally 15 seconds or greater, optionally 18 seconds or greater, or optionally 20 seconds or greater, at room temperature. In some embodiments of the methods provided herein, the plunger is pushed for 20-30 seconds from when it is first pushed to when it stops.

[0048] In some embodiments of the methods provided herein, the plunger stops when thestopper reaches the distal end of the barrel of the pre-filled syringe. In some embodiments of the methods provided herein, the plunger stops when the thumb pad comes within 1 cm of the proximal end of the barrel of the pre-filled syringe.

[0049] In some embodiments of the methods provided herein, the needle is removed at thesame angle at which it was inserted. In some embodiments of the methods provided herein, the method further comprises covering the needle after removing the needle. In some embodiments of the methods provided herein, the needle is covered with a needle shield. In some embodiments of the methods provided herein, the method further comprising pressing gauze over the pinched site after removing the needle.

[0050] In some embodiments of the methods provided herein, the pre-filled syringe is storedat 2˚ C - 8˚ C prior to being placed at room temperature. In some embodiments of the methods provided herein, the pre-filled syringe is stored at 20˚ C - 30˚ C for up to 1 month.

[0051] In some embodiments of the methods provided herein, the subject has myastheniagravis. In some embodiments of the methods provided herein, the subject has generalized myasthenia gravis. In some embodiments of the methods provided herein, the subject is anti-acetylcholine receptor (AChR) antibody positive. In some embodiments of the methods provided herein, the subject shows a statistically significant improvement in MG-ADL responder rate after administration. In some embodiments of the methods provided herein, the subject that received administration belongs 10 BUSINESS.32923153.1to a group of subjects that shows a significant improvement in MG-ADL responder rate after administration.

[0052] In some embodiments of the methods provided herein, the subject shows reduction inerythema, swelling, and / or induration at the injection site in less than 30 minutes, optionally less than 45 minutes, optionally less than 60 minutes, optionally less than 75 minutes, or optionally less than 90 minutes. In some embodiments of the methods provided herein, the subject indicates no pain or mild pain immediately after the injection, optionally 5 minutes after the injection, or optionally 10 minutes after the injection. In some embodiments of the methods provided herein, the subject indicates that they would have the injection again.

[0053] In some embodiments of the methods provided herein, back leakage is minimal. Insome embodiments of the methods provided herein, back leakage is less than 15 μL, optionally less than 10 μL, optionally less than 8 μL, or optionally less than 5 μL.

[0054] In some embodiments of the methods provided herein, leakage is minimal. In someembodiments of the methods provided herein, leakage is less than 25 μL, optionally leakage is less than 20 μL, optionally leakage is less than 15 μL, optionally less than 10 μL, optionally less than 8 μL, or optionally less than 5 μL.

[0055] In some embodiments of the methods provided herein, the pre-filled syringecontaining the liquid pharmaceutical formulation comprising the FcRn antagonist and the hyaluronidase is an approved product. In some embodiments of the methods provided herein, the approved product is approved for the treatment of gMG in an adult. In some embodiments of the methods provided herein, the adult is anti-AChR antibody positive.

[0056] In some embodiments of the methods provided herein, administration of the liquidpharmaceutical formulation to the subject with the pre-filled syringe provides a dose of FcRn antagonist and hyaluronidase bioequivalent to the same dose of the FcRn antagonist and hyaluronidase administered to a second subject using a second formulation administered in a syringe that is filled from a vial just prior to administration.

[0057] In some embodiments of the methods provided herein, administration of the liquidpharmaceutical formulation to the subject with the pre-filled syringe provides a dose of FcRn antagonist and hyaluronidase with increased Cmax and AUC when compared to the same dose of FcRn antagonist and hyaluronidase administered to a second subject using a second formulation administered in a syringe that is filled from a vial just prior to administration. 11 BUSINESS.32923153.1

[0058] Also provided herein are methods of administering efgartigimod and hyaluronidase ina pre-filled syringe to a subject comprising discarding a first pre-filled syringe when the first pre- filled syringe is cracked, broken, or damaged; replacing the first pre-filled syringe with a second pre- filled syringe that is not cracked, broken, or damaged; and administering the efgartigimod and the hyaluronidase to the subject from the second pre-filled syringe. In some embodiments, the first pre- filled syringe is missing a syringe cap.

[0059] Also provided herein are methods of administering efgartigimod and hyaluronidase ina pre-filled syringe to a subject comprising discarding a first pre-filled syringe when the date of administration is after an expiration date of the first pre-filled syringe; replacing the first pre-filled syringe with a second pre-filled syringe when the date of administration is before an expiration date of the second pre-filled syringe; and administering the efgartigimod and the hyaluronidase to the subject from the second pre-filled syringe.

[0060] Also provided herein are methods of administering efgartigimod and hyaluronidase ina pre-filled syringe to a subject comprising discarding a first pre-filled syringe when the efgartigimod and hyaluronidase inside the first pre-filled syringe are discolored and / or contains particles; replacing the first pre-filled syringe with a second pre-filled syringe wherein the efgartigimod and the hyaluronidase inside the second pre-filled syringe is not discolored and / or does not contain particles; and administering the efgartigimod and the hyaluronidase to the subject from the second pre-filled syringe. In some embodiments, the efgartigimod and hyaluronidase inside the syringe are not clear to light yellow in color.

[0061] In some embodiments of the methods provided herein, the administration is performedonce weekly for 4 weeks.

[0062] Also provided herein are methods of administering efgartigimod and hyaluronidase toa subject, the method comprising subcutaneously injecting the efgartigimod and hyaluronidase for a duration of administration of between 20 and 30 seconds.

[0063] Also provided herein is an FcRn antagonist for use in a method of treating anautoimmune disease in a subject in need thereof, wherein the FcRn antagonist is administered subcutaneously to the subject using a pre-filled syringe as described herein. In some embodiments, the FcRn antagonist is for use according to the methods described herein. In some embodiments, the FcRn antagonist is administered using the pre-filled syringe and the duration of administration is no more than 30 seconds, optionally no more than 28 seconds, or optionally no more than 25 seconds. In some embodiments, the FcRn antagonist is administered with the pre-filled syringe and the duration 12 BUSINESS.32923153.1of administration is 15 seconds or greater, optionally 18 seconds or greater, or optionally 20 seconds or greater. In some embodiments, the FcRn antagonist is administered with the pre-filled syringe and the duration of administration is 20-30, 20-28, or 20-25 seconds. In some embodiments, the pre-filled syringe is a part of a kit as described herein. In some embodiments, the pre-filled syringe is placed at room temperature for at least 30 minutes prior to administration. In some embodiments, the autoimmune disease is myasthenia gravis.

[0064] Also provided herein is efgartigimod for use in a method of treating an autoimmunedisease in a subject in need thereof, wherein the efgartigimod is administered to the subject by subcutaneous injection and the duration of administration is 20-30, 20-28, or 20-25 seconds. In some embodiments, the efgartigimod is administered in combination with hyaluronidase. In some embodiments, the autoimmune disease is myasthenia gravis.

[0065] In some embodiments of the methods provided herein, the liquid pharmaceuticalformulation or efgartigimod is administered by the subject to themselves.

[0066] Also provided herein is a liquid pharmaceutical formulation comprising about 200mg / mL efgartigimod, about 2,000 U / mL rHuPH20, about 10.5 mg / mL L-arginine hydrochloride, about 1.4 mg / mL L-histidine, about 2.2 mg / mL L-histidine hydrochloride monohydrate, about 1.5 mg / mL L-methionine, about 0.4 mg / mL polysorbate 80, about 4.1 mg / mL sodium chloride, and about 20.5 mg / mL sucrose, at about pH 6.0.

[0067] Also provided herein is liquid pharmaceutical formulation comprising about 200mg / mL efgartigimod, about 2,000 U / mL rHuPH20, about 50 mM L-arginine, about 20 mM L- histidine, about 10 mM L-methionine, about 0.04% polysorbate 80, about 70 mM sodium chloride, and about 60 mM sucrose.

[0068] Also provided herein is a liquid pharmaceutical formulation comprising about 200mg / mL efgartigimod, about 2,000 U / mL rHuPH20, about 50 mM L-arginine hydrochloride, about 20 mM L-histidine and L-histidine hydrochloride monohydrate, about 10 mM L-methionine, about 0.04% polysorbate 80, about 70 mM sodium chloride, and about 60 mM sucrose.

[0069] Also provided herein is a liquid pharmaceutical formulation comprising 200 mg / mLefgartigimod, 2,000 U / mL rHuPH20, 10.5 mg / mL L-arginine hydrochloride, 1.4 mg / mL L-histidine, 2.2 mg / mL L-histidine hydrochloride monohydrate, 1.5 mg / mL L-methionine, 0.4 mg / mL polysorbate 80, 4.1 mg / mL sodium chloride, and 20.5 mg / mL sucrose, at pH 6.0. 13 BUSINESS.32923153.1

[0070] Also provided herein is a liquid pharmaceutical formulation comprising 200 mg / mLefgartigimod, 2,000 U / mL rHuPH20, 50 mM L-arginine, 20 mM L-histidine, 10 mM L-methionine, 0.04% polysorbate 80, 70 mM sodium chloride, and 60 mM sucrose.

[0071] Also provided herein is a liquid pharmaceutical formulation comprising 200 mg / mLefgartigimod, 2,000 U / mL rHuPH20, 50 mM L-arginine hydrochloride, 20 mM L-histidine and L- histidine hydrochloride monohydrate, 10 mM L-methionine, 0.04% polysorbate 80, 70 mM sodium chloride, and 60 mM sucrose.

[0072] Also provided herein is a method of treating gMG in a subject in need thereofcomprising administering to the subject the liquid pharmaceutical compositions described herein. In some embodiments, the subject is an adult. In some embodiments, the adult is anti-AChR antibody positive. In some embodiments, the administration is performed once weekly for 4 weeks.

[0073] In some embodiments, efgartigimod for use in treating gMG, wherein the efgartigimodis contained in the liquid pharmaceutical compositions described herein. In some embodiments, the subject is an adult. In some embodiments, the adult is anti-AChR antibody positive. In some embodiments, the administration is performed once weekly for 4 weeks.

[0074] Also provided herein is an approved product comprising a pre-filled syringecontaining a liquid pharmaceutical formulation comprising a human neonatal Fc receptor (FcRn) antagonist and a hyaluronidase, wherein the FcRn antagonist is efgartigimod.

[0075] In some embodiments, the hyaluronidase comprises recombinant human PH20(rHuPH20).

[0076] In some embodiments, the liquid pharmaceutical formulation comprises 1000 mg ofefgartigimod. In some embodiments, the liquid pharmaceutical formulation comprises 200 mg / mL of efgartigimod. In some embodiments, the liquid pharmaceutical formulation comprises 10,000 Units of the hyaluronidase. In some embodiments, the liquid pharmaceutical formulation comprises 2,000 Units / mL of the hyaluronidase. In some embodiments, the liquid pharmaceutical formulation comprises 10,000 Units of rHuPH20. In some embodiments, the liquid pharmaceutical formulation comprises 2,000 Units / mL of rHuPH20. In some embodiments, the liquid pharmaceutical formulation comprises 200 mg / mL efgartigimod, 2000 U / mL rHuPH20, 10.5 mg / mL L-arginine hydrochloride, 1.4 mg / mL L-histidine, 2.2 mg / mL L-histidine hydrochloride monohydrate, 1.5 mg / mL L- methionine, 0.4 mg / mL polysorbate 80, 4.1 mg / mL sodium chloride, 20.5 mg sucrose, and water for injection, USP, at a pH of 6.0. 14 BUSINESS.32923153.1

[0077] Also provided herein is a method of treating gMG in a subject in need thereofcomprising administering to the subject the approved product disclosed herein. In certain embodiments, the patient is anti-AChR antibody positive.

[0078] In some embodiments, the approved product is for use in a method of treating gMG ina subject in need thereof. In some embodiments, the patient is anti-AChR antibody positive. BRIEF DESCRIPTION OF DRAWINGS

[0079] FIG. 1 is a schematic of the parts of the prefilled syringe and the 25G, 5 / 8” length, thinwall safety needle (not provided with syringe).

[0080] FIG.2A-FIG.2D are schematics showing how to prepare the prefilled syringe and needle.FIG.2A shows how to remove the needle from the packaging. FIG.2B shows how to snap off the prefilled syringe cap. FIG.2C shows how to attach the needle to the prefilled syringe. FIG.2D shows the attached needle.

[0081] FIG. 3A-FIG. 3C are schematics showing how to prepare for the injection. FIG. 3Ashows areas on the abdomen that may be used for the injection site. FIG.3B shows how to pull the needle shield back. FIG.3C shows how to pull the clear needle cap.

[0082] FIG. 4A-FIG. 4C are schematics showing how to administer the injection. FIG. 4Ashows how to pinch the cleaned injection site and insert the needle into the pinched skin. FIG. 4B shows how to push on the plunger to administer the injection. FIG. 4C shows how to remove the needle from the skin.

[0083] FIG. 5A-FIG. 5B are schematics showing how to dispose of the syringe. FIG. 5A showshow to push the needle shield over the needle. FIG. 5B shows how to dispose of the syringe in an FDA-cleared sharps disposal container.

[0084] FIG. 6 is a schematic of the study design conducted to assess pharmacokinetics (PK) ofthe efgartigimod PH20 Gen1 SC (Vial) and Gen1.1 SC pre-filled syringe (PFS) formulations.

[0085] FIG. 7A-FIG. 7D are graphs showing PK and PD results from the study of efgartigimodPH20 Gen1 SC (Vial) and Gen1.1 SC (PFS) formulations. FIG.7A is a graph showing mean blood concentration of efgartigimod (in µg / mL) over time following a single 1000 mg efgartigimod PH20 SC injection. FIG.7B is a box-plot comparison of the Cmax parameter (in µg / mL) of Vial and PFS formulations. FIG.7C is a box-plot comparison of the AUC0-infparameter (in µg.h / mL) of Vial and PFS formulations. n = 60 for each of Vial and PFS formulations. FIG.7D is a graph showing mean 15 BUSINESS.32923153.1percent change from baseline in total IgG over time following a single 1000 mg efgartigimod PH20 SC injection.

[0086] FIG. 8 is a schematic of the study design conducted to assess pharmacokinetics (PK) ofthe efgartigimod PH20 Gen1 SC (Vial) and Gen2 SC pre-filled syringe (PFS) formulations.

[0087] FIG. 9A-FIG. 9C are graphs showing PK results from the study of efgartigimod PH20Gen1 SC (Vial) and Gen2 SC (PFS) formulations. FIG. 9A is a graph showing mean blood concentration of efgartigimod (in µg / mL) over time following a single 1000 mg efgartigimod PH20 SC injection. FIG.9B is a box-plot comparison of the Cmax parameter (in µg / mL) of Vial and PFS formulations. FIG.9C is a box-plot comparison of the AUC0-inf parameter (in µg.h / mL) of Vial and PFS formulations. n = 70 for Vial and 72 for PFS formulations.

[0088] FIG. 10 is a schematic of the phase 1, single center, randomized, open label, crossoverstudy in healthy adults to assess the feasibility of different speeds of subcutaneous injection for efgartigimod PH20 SC.

[0089] FIG. 11 is a graph showing the average volume of fluid leakage (backflow) in mL foreach of the 4 tested injection speeds in Periods 1 and 2.

[0090] FIG.12A-FIG. 12B are graphs showing self-reported local pain as assessed by numericalrating scale (NRS) at different timepoints before and after the SC injection in period 1 (FIG. 12A) and period 2 (FIG.12B).

[0091] FIG. 13A-FIG. 13B are graphs showing an overview of treatment emergent adverseevents (TEAE) during period 1 (FIG.13A) and period 2 (FIG.13B) of the study assessing injection speeds.

[0092] FIG. 14 is a graph showing when break loose force (BLF) and mean gliding force (MGF)were determined.

[0093] FIG. 15 is a graph showing temperature of a PFS in function of equilibration time (ET) atroom temperature (RT).

[0094] FIG. 16A-FIG. 16C are graphs showing BLF and MGF at 15 minutes, 30 minutes, and60 minutes of ET at RT. FIG. 16A shows average BLGF profile of PFS with a BD 25G thin wall needle at an extrusion speed of 100 mm / min after 15 minutes ET (top), 30 minutes ET (middle) and 60 minutes of ET (bottom). FIG.16B shows BLF at 15 minutes, 30 minutes, and 60 minutes of ET at RT for PFS with a BD 25G thin wall needle at an extrusion speed of 100 mm / min. FIG.16C shows MGF at 15 minutes, 30 minutes, and 60 minutes of ET at RT for PFS with a BD 25G thin wall needle at an extrusion speed of 100 mm / min. 16 BUSINESS.32923153.1

[0095] FIG.17A-FIG. 17B are graphs showing viscosity of a liquid formulation of efgartigimodat 15 minutes, 30 minutes, and 60 minutes of ET at RT and at various temperatures. FIG.17A shows viscosity of 200 mg / mL efgartigimod at 15 minutes, 30 minutes, and 60 minutes of ET at RT. FIG. 17B shows viscosity of 200 mg / mL efgartigimod at 18.5 ˚C, 20.0 ˚C, and 22.0 ˚C.

[0096] FIG. 18A-FIG. 18B are bar graphs showing BLF and MGF of various needles at variousinjection speeds. FIG. 18A shows BLF at of various needles at various injection speeds. FIG. 18B shows MGF at of various needles at various injection speeds.

[0097] FIG. 19A-FIG. 19C are graphs showing BLF and MGF profiles of various needles atvarious injection speeds. FIG.19A shows BLF and MGF profiles of 24G regular wall (RW), BD 25G thin wall (TW-BD), McKesson 25G thin wall (TW-MK), 25G extra thin wall (ETW) and 25G ultra thin wall (UTW) needle at an extrusion speed of 150 mm / min. FIG. 19B shows BLF and MGF profiles of the same needles at an extrusion speed of 100 mm / min. FIG.19C shows BLF and MGF profiles of the same needles at an extrusion speed of 50 mm / min. DETAILED DESCRIPTION Definitions

[0098] Unless defined otherwise, all technical and scientific terms used herein have the samemeaning as is commonly understood by one skilled in the art in the technical field of the invention.

[0099] As used herein, the term “pre-filled syringe” or “prefilled syringe” refers to a syringethat is supplied already loaded with the substance to be injected. In some embodiments, the syringe is designed to be discarded after one use. In some embodiments, the substance to be injected is a single dose of a medication. In some embodiments, the single dose is of an FcRn antagonist and a hyaluronidase. In some embodiments, the single dose is of efgartigimod and a recombinant human hyaluronidase. In some embodiments, the single dose is of efgartigimod SC Gen2.

[0100] As used herein, the term “syringe” refers to a single-acting reciprocating pumpcomprising a plunger that fits within a barrel. The plunger can be linearly pulled and pushed along the inside of the barrel, allowing the syringe to take in and expel liquid or gas through a nozzle at the distal end of the syringe. The plunger seals with an interior surface of the barrel, so as to define a volume that varies when the plunger moves within the barrel.

[0101] In some embodiments, the syringe comprises a syringe body and a plunger. In someembodiments, the syringe body comprises the barrel with an interior volume, a distal end and a proximal end. In some embodiments, the interior volume of the barrel contains the substance to be 17 BUSINESS.32923153.1injected. In some embodiments, the plunger is inserted through the proximal end of the syringe body into the barrel. In some embodiments, the proximal end of the syringe body comprises a finger flange. In some embodiments, the distal end of the syringe body comprises a nozzle. In some embodiments, the syringe body is made of a transparent or translucent material.

[0102] As used herein, the term “barrel” refers to a cylindrical tube containing an interiorvolume that in some embodiments contains a substance to be injected.

[0103] As used herein, the term “plunger” refers to a piston that can be linearly pulled andpushed along the inside of the barrel, allowing the syringe to take in and expel liquid or gas through a nozzle at the distal end of the syringe. In some embodiments, the plunger comprises a stopper at its distal end. In some embodiments, the plunger comprises a thumb pad at its proximal end.

[0104] As used herein, the term “finger flange” refers to a pair of protrusions extendingradially from the body of the syringe that allow the user to grip the syringe and administer an injection.

[0105] As used herein, the term “nozzle” refers to a tip for expelling fluid disposed within theinterior volume of the barrel. In some embodiments, the nozzle has an interior volume of 0.1-0.5 mL or 0.1-0.3 mL. In some embodiments, the nozzle has an interior volume of about 0.2 mL. In some embodiments, the nozzle has an interior volume of 0.2 mL.

[0106] As used herein, the term “thumb pad” refers to a surface perpendicular to and at theproximal end of the plunger that allows the user to comfortably press the plunger and administer an injection.

[0107] As used herein, the term “stopper” refers to a portion of the distal end of the plungerthat is in contact with the barrel and the substance to be injected during the injection. In some embodiments, the stopper prevents or reduces the amount of substance to be injected that leaks around the plunger during injection. An amount of substance to be injected that leaks around the plunger is referred to herein as “back leakage.” In some embodiments, the amount of back leakage that occurs when using the pre-filled syringe is minimal. In some embodiments, the amount of back leakage is less than 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 μL when 5 mL of the substance is injected.

[0108] As used herein, the term “extractable volume” is the volume contained within theinterior volume of the barrel of the syringe and any volume within the nozzle that is expelled from the syringe when the plunger is pressed starting at the proximal end of the syringe body into the interior volume of the barrel of the syringe body until the plunger is stopped at the distal end of the syringe body. In some embodiments, the extractable volume is 4.0-6.0 mL, 4.1-5.9 mL, 4.2-5.8 mL, 4.3-5.7 mL, 4.4-5.6 mL, 4.5-5.5 mL, 4.6-5.4 mL 4.7-5.3 mL, 4.8-5.2 mL, or 4.9-5.1 mL. In some 18 BUSINESS.32923153.1embodiments, the extractable volume is about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, about 5.0, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, or about 6.0 mL. In some embodiments, the extractable volume is 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, or 6.0 mL. In some embodiments, the extractable volume is about 5.0 mL. In some embodiments, the extractable volume is 5.0 mL.

[0109] In some embodiments, the syringe further comprises a collar around the outside of thenozzle. As used herein, the term “collar” refers to a connector that allows tubes or needles to be attached at the distal end of the syringe. In some embodiments, needles are attached to the collar by twisting the needle into grooves positioned on the collar.

[0110] In some embodiments, the nozzle is covered with a cap. In some embodiments, thecap snaps off the nozzle when the nozzle is to be exposed. In some embodiments, the cap twists off the nozzle when the nozzle is to be exposed. In some embodiments, the collar is covered with a cap. In some embodiments, the cap snaps off the collar when the collar is to be exposed. In some embodiments, the cap twists off the collar when the collar is to be exposed.

[0111] In some embodiments, the collar of the syringe is configured to hold a needle in place.In some embodiments, the needle is a 24G or a 25G needle. In some embodiments, the needle is 5 / 8” in length. In some embodiments, the needle is regular wall, thin wall, extra thin wall, or ultra thin wall. In some embodiments, the needle is 24G regular wall, 25G regular wall, 25G thin wall, 25G extra thin wall, or 25G ultra thin wall. In some embodiments, the needle is 25G thin wall.

[0112] In some embodiments, the needle is provided with a needle cap. As used herein, theterm “needle cap” refers to a cover for a needle that prevents the needle being damaged, losing sterility, or being inserted inadvertently prior to injection. In some embodiments, the needle cap is made of transparent or translucent material.

[0113] In some embodiments, the needle is provided with a needle shield. As used herein, theterm “needle shield” refers to a flange that is attached to the proximal base of a needle. The flange comprises one or more hinges that allows the needle to be exposed for injection, but then covered after injection has occurred. In some embodiments, the needle shield has a catch that holds it in a position covering the needle. In some embodiments, the needle shield has a catch that holds it in a position exposing the needle. In some embodiments, the needle shield is held in a position holding the needle cap in place prior to injection. In order to remove the needle cap, the needle shield is swivelled so as to no longer block access to the needle cap (see e.g., FIG.3B). 19 BUSINESS.32923153.1

[0114] In some embodiments, the needle is provided separately from the pre-filled syringe.

[0115] In some embodiments, the pre-filled syringe is an auto-injector. In some embodiments,the auto-injector comprises a luer fit needle. In some embodiments, the auto-injector is button activated. In some embodiments, the auto-injector comprises post-delivery sharps protection.

[0116] In certain embodiments, efgartigimod is administered alone. Alternatively, in certainembodiments, efgartigimod may be administered co-formulated with hyaluronidase, for example, rHuPH20. The co-formulated material will allow SC dosing of larger volumes and / or with faster injection times.

[0117] rHuPH20 is the active ingredient of Halozyme’s commercial product HYLENEX®recombinant (hyaluronidase human injection), referred to as HYLENEX®, which was approved by FDA for marketed use in the U.S. in December 2005. HYLENEX® is a tissue permeability modifier indicated as an adjuvant in SC fluid administration for achieving hydration, to increase the dispersion and absorption of other injected drugs, and in SC urography, for improving resorption of radiopaque agents.

[0118] rHuPH20 is a recombinant enzyme human hyaluronidase produced by geneticallyengineered Chinese hamster ovary (CHO) cells containing a deoxyribonucleic plasmid encoding a soluble fragment of human hyaluronidase (posterior head protein 20 [PH20]).

[0119] The HZ202 rHuPH20 DS is currently registered in HYLENEX® and other biologicdrug products co-formulated with rHuPH20 DS. As such, in certain embodiments HZ202 rHuPH20 DS is used in the efgartigimod / rHuPH20 co-formulated product for SC administration (i.e., efgartigimod PH20 SC).

[0120] Provided in the co-formulations, combinations, uses and methods herein are solublehyaluronidases. Soluble hyaluronidases include any that, upon expression, are secreted from a cell and exist in soluble form. Such soluble hyaluronidases include, but are not limited to, bacterial soluble hyaluronidases, non-human soluble hyaluronidases, such as bovine PH20 and ovine PH20, human soluble PH20, and variants thereof. Generally soluble forms of PH20 are produced using protein expression systems that facilitate correct N-glycosylation to ensure the polypeptide retains activity, since glycosylation is important for the catalytic activity and stability of hyaluronidases. Such cells include, for example Chinese Hamster Ovary (CHO) cells (e.g., DG44 CHO cells).

[0121] In some embodiments, rHuPH20 refers to the composition produced upon expressionin a cell, such as a CHO cell, of nucleic acid encoding residues 36-482 of SEQ ID NO: 24, generally linked to the native or a heterologous signal sequence (residues 1-35 of SEQ ID NO: 24). rHuPH20 20 BUSINESS.32923153.1is produced by expression of a nucleic acid molecule, such as encoding amino acids 1-482 (set forth in SEQ ID NO: 24) in a mammalian cell. Translational processing removes the 35 amino acid signal sequence. As produced in the culture medium there is heterogeneity at the C-terminus such that the product, designated rHuPH20, includes a mixture of species that can include any one or more of the polypeptides 36-480, 36-481, and 36-482 of SEQ ID NO: 24, and some shorter polypeptides, in various abundance. Typically, rHuPH20 is produced in cells that facilitate correct N-glycosylation to retain activity, such as CHO cells (e.g., DG44 CHO cells). In some embodiments, one of the most abundant species is the 446 amino acid polypeptide corresponding to residues 36-481 of SEQ ID NO: 24. In some embodiments, rHuPH20 refers to polypeptides that are soluble or secreted upon expression in a mammalian cell and have at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity with residues 36-482 of SEQ ID NO: 24. In some embodiments, the rHuPH20 is the 447 amino acid polypeptide of SEQ ID NO: 25. Table 1. Exemplary hyaluronidase sequences SEQ ID NO: Amino Acid Sequence F L K Y T T G V S

[0122] As used herein, the term “approved product” refers to a biological product approvedby at least one regulatory agency for introduction into commerce. As used herein, the term “regulatory 21 BUSINESS.32923153.1agency” refers to one of the following: the United States Food and Drug Administration (FDA), the European Medicines Agency of the European Union (EMA), the Pharmaceuticals and Medical Devices Agency of Japan (PMDA), and the National Medical Products Administration of China (NMPA).

[0123] As used herein, the terms “biological product” or “biologic” can be usedinterchangeably to refer to a wide range of products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cells and tissues. A biological product comprises a population of biological molecules (e.g., a population of individual protein molecules). Many therapeutic proteins are produced by recombinant DNA technology in animal or microbial host cells. During the manufacturing process, these engineered host cells make many copies of a therapeutic protein with the same amino acid sequence. Changes can occur to one or more amino acids in a given protein through post-translational modifications, such as glycosylation. Therefore, although a single protein is being manufactured, the individual protein molecules can be slightly different from each other. The resulting biological product ends up being a mix of these individual protein molecules with various sugars attached to them. Other post-translational modifications, such as oxidation or deamidation, or truncations may also be present. This is true for approved products, reference products, biosimilars, and interchangeable biosimilars.

[0124] A biological product may comprise other active or inactive ingredients. Inactiveingredients include formulation excipients. The term “dosage form,” as used herein refers to the physical form in which a biological product is produced and dispensed, such as, for example, an injectable, a tablet, or a capsule.

[0125] In some embodiments, the approved product is a biological product containingefgartigimod that has been approved for use in treating humans with myasthenia gravis and is formulated for delivery by subcutaneous injection in a 1,000 mg dose. An example of an “approved product” is the approved product described in Example 1.

[0126] In some embodiments, the approved product is provided in a single-dose vialcontaining 1000 mg of efgartigimod at a concentration of 200 mg / mL and 10,000 U of rHuPH20 at a concentration of 2,000 / mL and each milliliter of solution comprises: 22 BUSINESS.32923153.1L-arginine hydrochloride (10.5 mg), L-histidine (1.4 mg), L-histidine hydrochloride monohydrate (2.2 mg), L-methionine (1.5 mg), polysorbate 80 (0.4 mg), sodium chloride (4.1 mg), sucrose (20.5 mg), and water for injection, USP, at a pH of 6.0.

[0127] In some embodiments, the approved product is provided in a pre-filled syringecontaining 1000 mg of efgartigimod at a concentration of 200 mg / mL and 10,000 U of rHuPH20 at a concentration of 2,000 / mL and each milliliter of solution comprises: L-arginine hydrochloride (10.5 mg), L-histidine (1.4 mg), L-histidine hydrochloride monohydrate (2.2 mg), L-methionine (1.5 mg), polysorbate 80 (0.4 mg), sodium chloride (4.1 mg), sucrose (20.5 mg), and water for injection, USP, at a pH of 6.0.

[0128] In some embodiments, when the approved product is administered in a 1000 mgsubcutaneous injection dose to subjects or a patient population having myasthenia gravis, it induces a statistically significant increase in MG-ADL response rate, and / or in QMG response rate compared to the respective response rate in a patient population receiving placebo. In some embodiments, when the approved product is administered in a 10 mg / kg infusion dose to subjects or a patient populationhaving generalized myasthenia gravis, it induces an MG-ADL response rate of 67.7%, and a QMGresponse rate of 63.1%, compared to 29.7% and 14.1% response in a placebo population.

[0129] In some embodiments, when using the approved product, it is recommended to informpatients of hypersensitivity reactions and to monitor patients for hypersensitivity reactions duringadministration and for at least 30 minutes after administration. In some embodiments, when using the approved product, it is recommended to inform patients of hypersensitivity reactions and to monitorpatients for hypersensitivity reactions during administration and for 1 hour after administration, wherethe hypersensitivity reactions are selected from the group consisting of anaphylaxis and hypotension leading to syncope. If hypersensitivity is observed in a patient during or after administration of the approved product, appropriate measures to mitigate said hypersensitivity reactions are instituted, which include discontinuing use.

[0130] In some embodiments, when using the approved product, it is recommended tomonitor patients for infusion-related reactions during administration and for 1 hour afteradministration, where the reactions are selected from the group consisting of hypertension, chills, shivering, thoracic pain, abdominal pain, and back pain within an hour of administration. As used herein, the terms “thoracic pain” and “chest pain” are used interchangeably. If an infusion-related reaction is severe, the patient should discontinue treatment with the approved product and initiate appropriate therapy. If an infusion-related reaction is mild to moderate, the patient should be 23 BUSINESS.32923153.1rechallenged with the approved product with close clinical observation, slower infusion rates, and pre-medications.

[0131] In some embodiments, the approved product is further defined as follows:

[0132] -is provided in a pre-filled syringe containing 1000 mg of efgartigimod at aconcentration of 200 mg / mL and each milliliter of solution comprises: L-arginine hydrochloride (10.5 mg), L-histidine (1.4 mg), L-histidine hydrochloride monohydrate (2.2 mg), L-methionine (1.5 mg), polysorbate 80 (0.4 mg), sodium chloride (4.1 mg), sucrose (20.5 mg), and water for injection, USP, at a pH of 6.0; and -is contraindicated in patients with serious hypersensitivity to efgartigimod alfa products or to any formulation excipients thereof; and -when administered in a 1000 mg subcutaneous injection to subjects or a patient population havingmyasthenia gravis, induces a statistically significant increase in MG-ADL response rate, and / or inQMG response rate compared to the respective response rate in a patient population receiving placebo; and -when administered, may induce a hypersensitivity reaction selected from anaphylaxis and hypotension leading to syncope during or within an hour of administration; and -when administered, may induce an infusion-related reaction selected from hypertension, chills, shivering, thoracic pain, abdominal pain, and back pain during or within an hour of administration; and -when using, it is recommended to inform patients of hypersensitivity reactions and to monitorpatients for hypersensitivity reactions during administration and for 1 hour after administration, wherethe hypersensitivity reactions are selected from the group consisting of anaphylaxis and hypotension leading to syncope, and if hypersensitivity is observed in a patient during or after administration of the approved product, appropriate measures to mitigate said hypersensitivity reactions are instituted, which include discontinuing use.

[0133] In some embodiments, the approved product is a product approved under BiologicsLicense Application (BLA) 761304, EMA product number: EMEA / H / C / 005849, or VYVDURA approved in Japan on January 18, 2024.

[0134] As used herein, the term “biosimilar” refers to a biological product approved by aregulatory agency that is highly similar to and has no clinically meaningful differences from a reference product. A biosimilar is a type of approved product. A biosimilar can be shown to be highly similar to the reference product by analyzing (i.e., characterizing) the structure and function of both 24 BUSINESS.32923153.1the reference product and the proposed biosimilar and comparing characteristics of the products, such as purity, chemical identity, and bioactivity. Note that differences, such as oligosaccharide profiles, amino acid truncations or extensions, oxidation, deamidation, etc., may exist between biological products produced using different cell lines or manufacturing techniques and that a biological product may behave differently in patients if manufactured using a different cell line or a different methodology. However, differences, such as acceptable within-product variations, between the reference product and the proposed biosimilar can be present so long as the biosimilar is highly similar and has no clinically meaningful differences. Similarly, minor differences between the reference product and the proposed biosimilar in clinically inactive components are acceptable so long as the biosimilar is highly similar and has no clinically meaningful differences.

[0135] As used herein, “no clinically meaningful differences” is determined in terms of safety,purity, and potency. For example, a biosimilar is compared to and evaluated against a reference product to verify that the biosimilar has no clinically meaningful differences in terms of safety, purity, and potency from the reference product. In some embodiments, a determination of no clinically meaningful differences between a biosimilar and a reference product is based upon data derived from: (a) analytical studies that demonstrate that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components; (b) animal studies (including, for example, assessment of toxicity); and / or (c) a clinical study or studies (including, for example, assessment of immunogenicity and pharmacokinetics or pharmacodynamics) sufficient to demonstrate safety, purity, and potency in one or more appropriate conditions of use for which the reference product is licensed and for which licensure is sought for the biosimilar. A biosimilar may be an interchangeable biosimilar that may be substituted for the reference product at a pharmacy without intervention of a prescribing healthcare professional. To meet a standard of “interchangeability,” the biosimilar is expected to produce the same clinical result as the reference product in any given patient and, if the biosimilar is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the use of the biosimilar and the reference product is not greater than the risk of using the reference product without such alternation or switch. In some embodiments, the biosimilar utilizes the same mechanisms of action as the reference product for the proposed conditions of use, to the extent the mechanisms are known for the reference product. In some embodiments, the condition or conditions of use prescribed, recommended, or suggested in the labeling proposed for the biosimilar have been previously approved for the reference product. In some embodiments, the route of administration, the dosage form, and / or 25 BUSINESS.32923153.1the strength of a biosimilar are the same as those of the reference product and the biosimilar is manufactured, processed, packed, or held in a facility that meets standards designed to assure that the biosimilar continues to be safe, pure, and potent.

[0136] As used herein, "bioequivalent" or "bioequivalence" is defined as the absence of asignificant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site(s) of drug action when administered at the same molar dose under similar conditions in an appropriately designed study.

[0137] A determination of “biosimilarity” or “bioequivalence” or “interchangeability” maybe made according to any of the standards defined by the FDA, EMA, PMDA, or NMPA. A company seeking approval to market a generic equivalent or biosimilar in the United States must refer to the reference product in its 351(k) BLA. For example, a 351(k) BLA applicant relies on the FDA's finding that a previously approved product, i.e., the reference product, is safe and effective, and must demonstrate, among other things, that the proposed biosimilar is the same as the reference product in certain ways. Specifically, with limited exceptions, a biological product for which an 351(k) BLA is submitted must have, among other things, the same active ingredient(s), mechanism(s) of action for the proposed condition(s) of use (but only to the extent the mechanism(s) are known for the reference product), condition(s) of use, route of administration, dosage form, strength, and (with certain permissible differences) labeling as the reference product. In Europe, a company may choose to develop and seek marketing authorisation for a “biosimilar”, wherein a biosimilar is a biological medicinal product highly similar to a reference medicinal product. The reference medicinal product is a biological product already having been granted a marketing authorisation in the European Union (EU) on the basis of a complete dossier. The legal basis for authorisation of biosimilars in Europe comes from the provisions of Article 10(4) of Directive 2001 / 83 / EC and Article 6 of Regulation (EC) 726 / 2004. The legal basis of Article 10(4) of Directive 2001 / 83 / EC and Annex I, Part II, Section 4 of to the Directive lays down the requirements for Marketing Authorization Applications (MAAs) based on the demonstration of the similar nature of the two biological medicinal products. Comparability studies are needed to generate evidence substantiating the similar nature, in terms of quality, safety, and efficacy, of the similar biological medicinal product and the chosen reference medicinal product authorised in the EU.

[0138] The term “reference product” refers to a product that is approved by a regulatoryagency (e.g., the approved product) against which a proposed biosimilar is compared. A reference 26 BUSINESS.32923153.1product is approved based on, among other things, a full complement of safety and effectiveness data. A proposed biosimilar product is compared to, and evaluated against, a reference product to ensure that the product is highly similar and has no clinically meaningful differences. In some embodiments, the reference product is approved in at least one of the U.S., Europe, China, or Japan. In some embodiments, the reference product is an approved product as defined herein. In some embodiments, the reference product is a biological product, licensed in the United States under section 351(a) of the Public Health Service (PHS) Act, against which a biological product is evaluated in a BLA submitted under section 351(k) of the PHS Act (i.e., 351(k) BLA).

[0139] As used herein, the terms “label,” “product label,” or “approved product label” referto information provided to a patient and / or healthcare provider which provides relevant information regarding the approved product. Such information includes, without limitation, one or more of: the description of the approved product, clinical pharmacology, indications (uses for the approved product), contraindication (who should not take the approved product), warnings, precautions, adverse events (side effects), drug abuse and dependence, dosage and administration, use in pregnancy, use in nursing mothers, use in children and older patients, how the approved product is supplied, safety information for the patient, or any combination thereof. In some embodiments, the label identifies efgartigimod and provides instructions for its use in a patient.

[0140] As used herein, the term “FcRn” refers to a neonatal Fc receptor. Exemplary FcRnmolecules include human FcRn encoded by the FCGRT gene as set forth in RefSeq NM 004107. The amino acid sequence of the corresponding protein is set forth in RefSeq NP_004098.

[0141] As used herein, the term “FcRn antagonist” refers to any agent that binds specificallyto FcRn and inhibits the binding of immunoglobulin to FcRn (e.g., human FcRn).

[0142] As used herein, the term “Fc domain” refers to the portion of a single immunoglobulinheavy chain beginning in the hinge region and ending at the C-terminus of an antibody. Accordingly, a complete Fc domain comprises at least a portion of a hinge region (e.g., upper, middle, and / or lower hinge region), a CH2 domain, and a CH3 domain. In some embodiments, the term “Fc domain” refers to the portion of a single immunoglobulin heavy chain comprising both the CH2 and CH3 domains of an antibody. In some embodiments, the Fc domain comprises at least a portion of a hinge region (e.g., upper, middle, and / or lower hinge region), a CH2 domain, and a CH3 domain. In some embodiments, the Fc domain does not include the hinge region.

[0143] As used herein, the term “hinge region” refers to the portion of a heavy chain moleculethat joins the CH1 domain to the CH2 domain. In some embodiments, the hinge region is at most 70 27 BUSINESS.32923153.1amino acid residues in length. In some embodiments, this hinge region comprises approximately 11- 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 acid residues in length. In some embodiments, the hinge region is 15 amino acid residues in length. In some embodiments, the hinge region is 62 amino acid residues in length. Hinge regions can be subdivided into three distinct domains: upper, middle, and lower hinge regions. The FcRn antagonists of the instant disclosure can include all or any portion of a hinge region. In some embodiments, the hinge region is from an IgG1 antibody. In some embodiments, the hinge region comprises the amino acid sequence of EPKSCDKTHTCPPCP (SEQ ID NO: 23).

[0144] As used herein, the term “Fc region” refers to the portion of an immunoglobulinformed by the Fc domains of its two heavy chains. The Fc region can be a wild-type Fc region (native Fc region) or a variant Fc region. A native Fc region is homodimeric. The Fc region can be derived from any native immunoglobulin. In some embodiments, the Fc region is formed from an 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 constant region 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 a G1m1(a), G1m2(x), G1m3(f), or G1m17(z) allotype, see, e.g., Jefferis and Lefranc, 2009 and de Taeye et al., 2020.

[0145] As used herein, the term “variant Fc region” refers to an Fc region with one or morealteration(s) relative to a native Fc region. Alterations can include amino acid substitutions, additions and / or deletions, linkage of additional moieties, and / or alteration of the native glycans. The term encompasses heterodimeric Fc regions where each of the constituent Fc domains is different. The term also encompasses single chain Fc regions where the constituent Fc domains are linked together by a linker moiety.

[0146] As used herein the term “FcRn binding fragment” refers to a portion of an Fc regionthat is sufficient to confer FcRn binding.

[0147] As used herein, the term “EU position” refers to the amino acid position in the EUnumbering convention for the Fc region described in Edelman, GM et al., Proc. Natl. Acad. USA, 1969; 63, 78-85, and Kabat et al., in “Sequences of Proteins of Immunological Interest,” U.S. Dept. Health and Human Services, 5thedition, 1991. 28 BUSINESS.32923153.1

[0148] As used herein, the term “baseline” refers to a measurement in a patient, e.g., in apatient’s blood, prior to the first administration (e.g., intravenous administration) of a treatment (e.g., an FcRn antagonist).

[0149] As used herein, the term “treat,” “treating,” and “treatment” refer to therapeutic orpreventative measures described herein. The methods of “treatment” employ administration of a polypeptide to a subject having a disease or disorder, or predisposed to having such a disease or disorder, in order to prevent, cure, delay, reduce the severity of, or ameliorate one or more symptoms of the disease or disorder or recurring disease or disorder, or in order to prolong the survival of a subject beyond that expected in the absence of such treatment.

[0150] As used herein, the term “effective amount” in the context of the administration of atherapy to a subject refers to the amount of a therapy that achieves a desired prophylactic or therapeutic effect.

[0151] As used herein, the term “dose” or “dosing” refers to an amount of an agentadministered to a subject in a single administration.

[0152] As used herein, the terms “fixed dose” or “flat dose” both refer to a dose that does notvary based upon a characteristic (e.g., body mass, e.g., within a set range; sex; age, e.g., within a set range; etc.) of the subject.

[0153] As used herein, the term “subject” or “patient” or “participant” may be usedinterchangeably and includes any human or non-human animal. In an embodiment, the subject or patient or participant is a human or non-human mammal. In an embodiment, the subject or patient or participant is a human.

[0154] As used herein, the term “about” or “approximately” when referring to a measurablevalue, such as a dosage, encompasses variations of ±5% of a given value or range, as are appropriate to perform the methods disclosed herein.

[0155] As used herein, the term “single-dose vial” refers to a vial of liquid medicationintended for parenteral administration (e.g., subcutaneous injection) that is meant for use in a single patient for a single administration.

[0156] As used herein, the term “preservative free” refers to compositions (e.g.,pharmaceutical compositions) that do not contain amounts of preservatives that are detectable using methods known in the art.

[0157] As used herein, the term “MG-ADL response” refers to a reduction of ≥ 2 points onMG-ADL score compared to baseline, for at least 4 consecutive weeks, where the first of the 29 BUSINESS.32923153.1reductions occurs at the latest 1 week after the last treatment. The Myasthenia Gravis Activities of Daily Living (MG-ADL) scale is an 8-item patient-reported scale to assess MG symptoms and their effects on daily activities. It evaluates the capacity to perform different activities of daily living such as talking, chewing, swallowing, breathing, brushing the teeth / combing the hair, or arising from the chair and it also assesses double vision and eyelid droop. The 8 items of the MG-ADL were derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0-24, where higher scores indicate more severe impairments.

[0158] As used herein, the term “QMG response” refers to a reduction of ≥ 3 points on QMGscore compared to baseline, for at least 4 consecutive weeks, where the first of the reductions occurs at the latest 1 week after the last treatment. The Quantitative Myasthenia Gravis (QMG) scale is a standardized quantitative strength scoring system developed specifically for MG. The QMG has been validated and has been used by the investigators in several trials. It consists of 13 items that assess ocular, bulbar, and limb function. Out of the 13 items, 6 are timed tests of endurance measured in seconds. Each item has a possible score from 0-3. The total possible score is 39, where higher scores indicate more severe impairments.

[0159] As used herein, the term “Myasthenia Gravis Foundation of America (MGFA) clinicalclassification system” refers to the classification system designed by the Task Force of the Medical Scientific Advisory Board of the MGFA published in 2000 (Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America, Inc. Neurology 55: 16-23 (2000)). The MGFA classification system defines classes of MG based on clinical symptoms as follows: Class I- any ocular muscle weakness, all other muscle strength is normal; Class II- mild weakness affecting other than ocular muscles, may also have ocular muscle weakness of any severity; Class IIa- predominantly affecting limb muscles, axial muscles, or both, may also have lesser involvement of oropharyngeal muscles, respiratory muscles, or both; Class IIb- predominantly affecting oropharyngeal muscles, respiratory muscles, or both, may also have lesser or equal involvement of limb muscles, axial muscles, or both; Class III- moderate weakness affecting other than ocular muscles, may also have ocular muscle weakness of any severity; Class IIIa- predominantly affecting limb muscles, axial muscles, or both, may also have lesser involvement of oropharyngeal muscles, respiratory muscles, or both; Class IIIb- predominantly affecting oropharyngeal muscles, respiratory 30 BUSINESS.32923153.1muscles, or both, may also have lesser or equal involvement of limb muscles, axial muscles, or both; Class IV- severe weakness affecting other than ocular muscles, may also have ocular muscle weakness of any severity; Class IVa- predominantly affecting limb muscles, axial muscles, or both, may also have lesser involvement of oropharyngeal muscles, respiratory muscles, or both; Class IVb- predominantly affecting oropharyngeal muscles, respiratory muscles, or both, may also have lesser or equal involvement of limb muscles, axial muscles, or both; Class V- defined by intubation, with or without mechanical ventilation, except when employed during routine postoperative management. FcRn Antagonists

[0160] FcRn antagonists that are useful in the compositions, methods, and uses providedherein include variant Fc regions that bind to and inhibit FcRn. Any Fc region can be altered to produce a variant Fc region for use in the methods disclosed herein. In an embodiment, the Fc region is an IgG Fc region (e.g., a human IgG region). In an embodiment, the Fc region is selected from IgG1, IgG2, IgG3, and IgG4. In an embodiment, the Fc region is an IgG1 Fc region (e.g., a human IgG1 region). A variety of Fc region gene sequences (e.g., human constant region gene sequences) are available in the form of publicly accessible deposits.

[0161] An Fc region can be further truncated or internally deleted to produce a minimal FcRnbinding fragment thereof. The ability of an Fc-region fragment to bind to FcRn can be determined using any art recognized binding assay (e.g., ELISA).

[0162] To enhance the manufacturability of the FcRn antagonists disclosed herein, it ispreferable that the constituent Fc regions do not comprise any non-disulfide bonded cysteine residues. Accordingly, in an embodiment, the Fc regions do not comprise a free cysteine residue.

[0163] Any variant Fc region that binds specifically to FcRn with increased affinity andreduced pH dependence relative to the native (i.e., wild-type) Fc region can be used in the methods disclosed herein. In an embodiment, the variant Fc region comprises amino acid alterations, substitutions, insertions, and / or deletions that confer the desired characteristics. In some embodiments, the FcRn antagonist comprises or consists of a variant Fc region, or FcRn binding fragment thereof, which binds to FcRn with a higher affinity at pH 5.5 as compared to a corresponding wild-type Fc region. In some embodiments, the FcRn antagonist comprises or consists of a variant Fc region, or FcRn binding fragment thereof, which bind to FcRn with a higher affinity at pH 6.0 and / or at pH 7.4 as compared to a corresponding wild-type Fc region. In some embodiments, the FcRn 31 BUSINESS.32923153.1antagonist comprises or consists of a variant Fc region, or FcRn binding fragment thereof, which bind to FcRn with a higher affinity at both acidic and neutral pH.

[0164] In some embodiments, the variant Fc region is derived from the Fc region of any nativeimmunoglobulin. In some embodiments, the native immunoglobulin is a human immunoglobulin. In some embodiments, the immunoglobulin is IgG. In some embodiments, the immunoglobulin is human IgG. In some embodiments, the IgG is IgG1, IgG2, IgG3, or IgG4. In some embodiments, the human IgG is human IgG1, human IgG2, human IgG3, or human IgG4. In some embodiments, the variant Fc region varies from the human IgG1 Fc region. In some embodiments, the human IgG1 Fc region comprises a G1m1(a), G1m2(x), G1m3(f), or G1m17(z) allotype.

[0165] In an embodiment, the variant Fc region, or FcRn binding fragment thereof consists oftwo Fc domains.

[0166] In an embodiment, the variant Fc region comprises or consists of a first Fc domain anda second Fc domain which form a homodimer or heterodimer. In an embodiment, the first Fc domain and / or the second Fc domain comprise amino acids Y, T, E, K, and F at EU positions 252, 254, 256, 433, and 434, respectively. In an embodiment, the first Fc domain and / or the second Fc domain comprise amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436, respectively.

[0167] In some embodiments, the FcRn antagonists disclosed herein comprise or consist of atleast one Fc domain, wherein the amino acid sequence of the at least one Fc domain comprises or consists of the amino acid sequence of SEQ ID NO: 22, provided below in Table 2. Table 2 Amino Acid Sequence SEQ ID

[0168] In some embodiments, the FcRn antagonists disclosed herein comprise or consist of avariant Fc region comprising or consisting of a dimer of a first Fc domain and a second Fc domain, 32 BUSINESS.32923153.1wherein the amino acid sequence of the first and second Fc domain comprises or consists of the amino acid sequence of SEQ ID NO: 22.

[0169] In some embodiments, the FcRn antagonists disclosed herein comprise or consist ofan amino acid sequence at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% 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 sequence of the first and second Fc domain comprises or consists of an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 1-21 (see Table 3 below). In some embodiments, the dimer is a heterodimer or a homodimer. Table 3 Amino Acid Sequence SEQ ID NO:33 BUSINESS.32923153.1KTHTCPPCPAPELLGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEV 6 KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK34 BUSINESS.32923153.1VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM HEALKFHYTQKSLSLSP

[0170] In an embodiment, the first Fc domain and / or the second Fc domain comprise an aminoacid sequence independently selected from the group consisting of SEQ ID NOs: 1, 2, 3, and 4. In an 35 BUSINESS.32923153.1embodiment, the first Fc domain and the second Fc domain comprise an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 1, 2, 3, and 4.

[0171] In some embodiments, the FcRn antagonist comprises a population of FcRn antagonistmolecules. In some embodiments, an FcRn antagonist comprising a first Fc domain and a second Fc domain comprising an amino acid sequence independently selected from the group consisting of SEQ ID NOs: 1, 2, 3, and 4 is the predominant FcRn antagonist molecule in the population of FcRn antagonist molecules. In some embodiments, the predominant FcRn antagonist molecule makes up at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the population of FcRn antagonist molecules.

[0172] In an embodiment, the amino acid sequence of the Fc domains of the variant Fc regioncomprises the amino acid sequence of SEQ ID NO: 1. In an embodiment, the amino acid sequence of the Fc domains of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 1.

[0173] In an embodiment, the amino acid sequence of the Fc domains of the variant Fc regioncomprises the amino acid sequence of SEQ ID NO: 2. In an embodiment, the amino acid sequence of the Fc domains of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 2.

[0174] In an embodiment, the amino acid sequence of the Fc domains of the variant Fc regioncomprises the amino acid sequence of SEQ ID NO: 3. In an embodiment, the amino acid sequence of the Fc domains of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 3.

[0175] In an embodiment, the amino acid sequence of the Fc domains of the variant Fc regioncomprises the amino acid sequence of SEQ ID NO: 4. In an embodiment, the amino acid sequence of the Fc domains of the variant Fc region consists of the amino acid sequence of SEQ ID NO: 4.

[0176] In certain embodiments, the variant Fc region is a heterodimer, where the constituentFc domains are different from each other. Methods of producing Fc heterodimers are known in the art (see, e.g., US 8,216,805, which is incorporated by reference herein in its entirety). In an embodiment, the FcRn antagonist consists of a variant Fc region, wherein the variant Fc region consists of two Fc domains which form a heterodimer, wherein the amino acid sequence of each of the Fc domains is independently selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In an embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains which form a heterodimer, wherein the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In an 36 BUSINESS.32923153.1embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains which form a heterodimer, wherein the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 2, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 3, or SEQ ID NO: 4. In an embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains which form a heterodimer, wherein the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 3, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 4. In an embodiment, the FcRn antagonist consists of or comprises a variant Fc region, wherein the variant Fc region consists of or comprises two Fc domains which form a heterodimer, wherein the amino acid sequence of the first Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 4, and the amino acid sequence of the second Fc domain consists of or comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.

[0177] In an embodiment, the FcRn antagonist consists of or comprises a variant Fc region,wherein the variant Fc region consists of or comprises two Fc domains which form a homodimer, wherein the amino acid sequence of each of the Fc domains consists of or comprises the amino acid sequence of SEQ ID NO: 1.

[0178] In an embodiment, the FcRn antagonist consists of or comprises a variant Fc region,wherein the variant Fc region consists of or comprises two Fc domains which form a homodimer, wherein the amino acid sequence of each of the Fc domains consists of or comprises the amino acid sequence of SEQ ID NO: 2.

[0179] In an embodiment, the FcRn antagonist consists of or comprises a variant Fc region,wherein the variant Fc region consists of or comprises two Fc domains which form a homodimer, wherein the amino acid sequence of each of the Fc domains consists of or comprises the amino acid sequence of SEQ ID NO: 3.

[0180] In an embodiment, the FcRn antagonist consists of or comprises a variant Fc region,wherein the variant Fc region consists of or comprises two Fc domains which form a homodimer, wherein the amino acid sequence of each of the Fc domains consists of or comprises the amino acid sequence of SEQ ID NO: 4.

[0181] In some embodiments, the FcRn antagonist comprises glycanation on one or both ofthe Fc domains. In some embodiments, the FcRn antagonist molecules comprise glycanation at EU 37 BUSINESS.32923153.1position 297 on one or both of the Fc domains. In some embodiments, the glycanation comprises an N-glycan. In some embodiments, the N-glycan comprises a G0F N-glycan, G1F N-glycan, G2F N- glycan, or G0 N-glycan.

[0182] In some embodiments, the FcRn antagonist comprises or consists of a population ofFcRn antagonists, 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 antagonists comprise galactose. In some embodiments, the population comprises or consists of FcRn antagonists, 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 Fc domains of the FcRn antagonists comprise fucose.

[0183] In some embodiments, the FcRn antagonist lacks an amino acid at EU position 441 ofone or both Fc domains. In some embodiments, the FcRn antagonist comprises glycine and lysine at EU positions 440 and 441, respectively. In some embodiments, the FcRn antagonist lacks amino acids at EU positions 440 and 441. In some embodiments, the FcRn antagonist comprises amidated proline at EU position 439. In some embodiments, the FcRn antagonist lacks amino acids at EU positions 440 and 441 and comprises amidated proline at EU position 439.

[0184] In some embodiments, the FcRn antagonist comprises aspartate, lysine, threonine,histidine, threonine, and cysteine at EU positions 221, 222, 223, 224, 225, and 226, respectively. In some embodiments, the FcRn antagonist lacks an amino acid at EU positions 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 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 lacks amino acids at EU positions 221- 224, and comprises threonine and cysteine at EU positions 225 and 226, respectively. In some embodiments, the FcRn antagonist lacks amino acids at EU positions 221, 222, 223, 224, 225, and 226.

[0185] In some embodiments, the FcRn antagonist is a population of FcRn antagonistmolecules. 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, 38 BUSINESS.32923153.117, 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.

[0186] In some embodiments, a first subpopulation of FcRn antagonist molecules comprisesor 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 domain comprises or consists of an amino acid sequence 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.

[0187] In some embodiments, a second subpopulation of FcRn antagonist moleculescomprises 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 the first and second Fc domain comprises or consists of an amino acid sequence at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NOs: 3 and 13, respectively.

[0188] In some embodiments, a third subpopulation of FcRn antagonist molecules comprisesor 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 the first and second Fc domain comprises or consists of an amino acid sequence at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NOs: 3 and 10, respectively.

[0189] In some embodiments, a fourth subpopulation of FcRn antagonist moleculescomprises 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 domain comprises or consists of an amino acid sequence 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 deaminated.

[0190] In some embodiments, a fifth subpopulation of FcRn antagonist molecules comprisesor 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 the first and second Fc domain comprises or consists of an amino acid sequence 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 asparagine residue in each FcRn antagonist molecule in the fifth subpopulation are deaminated.

[0191] In some embodiments, a sixth subpopulation of FcRn antagonist molecules comprisesor consists of a variant Fc region comprising or consisting of a dimer of a first Fc domain and a second 39 BUSINESS.32923153.1Fc domain, wherein the amino acid sequence of the first and second Fc domain comprises or consists of an amino acid sequence at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NOs: 2 and 3, respectively.

[0192] In some embodiments, a seventh subpopulation of FcRn antagonist moleculescomprises 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 the first and second Fc domain comprises or consists of an amino acid sequence 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 seventh subpopulation is oxidized.

[0193] In some embodiments, an eighth subpopulation of FcRn antagonist moleculescomprises 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 domain comprises or consists of an amino acid sequence 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.

[0194] In some embodiments, a ninth subpopulation of FcRn antagonist molecules comprisesor 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 the first and second Fc domain comprises or consists of an amino acid sequence at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NOs: 3 and 7, respectively.

[0195] In some embodiments, a tenth subpopulation of FcRn antagonist molecules comprisesor 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 the first and second Fc domain comprises or consists of an amino acid sequence at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence 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.

[0196] In some embodiments, an eleventh subpopulation of FcRn antagonist moleculescomprises 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 domain comprises or consists of an amino acid sequence 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 40 BUSINESS.32923153.1amino acid residues, independently selected from a methionine residue or a tryptophan residue, in each FcRn antagonist molecule in the eleventh subpopulation is oxidized.

[0197] In some embodiments, a first subpopulation of FcRn antagonist molecules comprisesor 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 domain comprises or consists of the amino acid sequence of SEQ ID NO: 3.

[0198] In some embodiments, a second subpopulation of FcRn antagonist moleculescomprises 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 the first and second Fc domain comprises or consists of the amino acid sequence of SEQ ID NOs: 3 and 13, respectively.

[0199] In some embodiments, a third subpopulation of FcRn antagonist molecules comprisesor 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 the first and second Fc domain comprises or consists of the amino acid sequence of SEQ ID NOs: 3 and 10, respectively.

[0200] In some embodiments, a fourth subpopulation of FcRn antagonist moleculescomprises 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 domain 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 deaminated.

[0201] In some embodiments, a fifth subpopulation of FcRn antagonist molecules comprisesor 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 the first and second Fc domain comprises or consists of the amino acid sequence of SEQ ID NO: 3, and wherein one asparagine residue in each FcRn antagonist molecule in the fifth subpopulation is deaminated.

[0202] In some embodiments, a sixth subpopulation of FcRn antagonist molecules comprisesor 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 the first and second Fc domain comprises or consists of the amino acid sequence of SEQ ID NOs: 2 and 3, respectively.

[0203] In some embodiments, a seventh subpopulation of FcRn antagonist moleculescomprises 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 the first and second Fc domain comprises or consists of the amino acid sequence of SEQ ID NO: 3, and wherein one methionine 41 BUSINESS.32923153.1residue or one tryptophan residue in each FcRn antagonist molecule in the seventh subpopulation is oxidized.

[0204] In some embodiments, an eighth subpopulation of FcRn antagonist moleculescomprises 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 domain comprises or consists of the amino acid sequence of SEQ ID NO: 2.

[0205] In some embodiments, a ninth subpopulation of FcRn antagonist molecules comprisesor 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 the first and second Fc domain comprises or consists of the amino acid sequence of SEQ ID NOs: 3 and 7, respectively.

[0206] In some embodiments, a tenth subpopulation of FcRn antagonist molecules comprisesor 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 the first and second Fc domain comprises or consists of the amino acid sequence 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.

[0207] In some embodiments, an eleventh subpopulation of FcRn antagonist moleculescomprises 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 domain comprises or consists of the amino acid sequence of SEQ ID NO: 3, and wherein two amino acid residues, independently selected from a methionine residue or a tryptophan residue in each FcRn antagonist molecule in the eleventh subpopulation is oxidized.

[0208] In some embodiments, the population of FcRn antagonist molecules comprises orconsists 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, 42 BUSINESS.32923153.1the 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.

[0209] In some embodiments, the population comprises or consists of the first and secondsubpopulations. 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.

[0210] In some embodiments, the population comprises or consists of the first and seventh,ninth, or eleventh subpopulations. In some embodiments, the population comprises or consists of the first, seventh, ninth, and eleventh subpopulations. 43 BUSINESS.32923153.1

[0211] In some embodiments, the first subpopulation makes up at least 40%, at least 45%, atleast 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 makes up 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 makes up 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 makes up 40%-90%, 50%-80%, or 55%-70% of the population of FcRn antagonist molecules. In some embodiments, the first subpopulation makes up 56.9%-68.3% or 59.5%-67.9% of the population of FcRn antagonist molecules.

[0212] In some embodiments, the second subpopulation makes up less than 3.0%, less than2.5%, 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 makes up 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 makes up 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 makes up 0.5%-3.0%, 1.0%-2.5%, or 1.0%-2.0% of the population of FcRn antagonist molecules. In some embodiments, the second subpopulation makes up 0.8%-2.0% or 0.8%-2.1% of the population of FcRn antagonist molecules.

[0213] In some embodiments, the third subpopulation makes up less than 3.0%, less than2.5%, 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 makes up 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 makes up 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 makes up 0.5%-3.0%, 1.0%-2.5%, or 1.0%-2.0% of the population of FcRn antagonist molecules. In some embodiments, the third subpopulation makes up 1.1%-2.1% or 1.0%-1.9% of the population of FcRn antagonist molecules.

[0214] In some embodiments, the fourth subpopulation makes up 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 makes up about 5%, about 4%, about 3%, about 2%, or about 1% of the population of FcRn antagonist molecules. In some embodiments, the fourth subpopulation 44 BUSINESS.32923153.1makes up 5%, 4%, 3%, 2%, or 1% of the population of FcRn antagonist molecules. In some embodiments, the fourth subpopulation makes up 1%-5%, 2%-4%, or 2%-3% of the population of FcRn antagonist molecules. In some embodiments, the fourth subpopulation makes up 2.1%-3.2% or 2.0%-3.1% of the population of FcRn antagonist molecules.

[0215] In some embodiments, the fifth subpopulation makes up 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 makes up 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 makes up 12%, 11%, 10%, 9%, 8%, 7%, 6%, or 5% of the population of FcRn antagonist molecules. In some embodiments, the fifth subpopulation makes up 5%-12%, 6%-10%, or 7%-8% of the population of FcRn antagonist molecules. In some embodiments, the fifth subpopulation makes up 6.8%-9.4% or 6.9%-8.7% of the population of FcRn antagonist molecules.

[0216] In some embodiments, the sixth subpopulation makes up 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 makes up 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 makes up 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 makes up 7%-17%, 10%-15%, or 11%-12% of the population of FcRn antagonist molecules. In some embodiments, the sixth subpopulation makes up 7.0%-14.0% or 10.0%-14.4% of the population of FcRn antagonist molecules.

[0217] In some embodiments, the seventh subpopulation makes up less than 6.0%, less than5.5%, 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. In some embodiments, the seventh subpopulation makes up 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 makes up 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 45 BUSINESS.32923153.1makes up 0.5%-5.5%, 1.0%-3.0%, or 1.5%-2.5% of the population of FcRn antagonist molecules. In some embodiments, the seventh subpopulation makes up 1.5%-5.5% or 1.4%-4.9% of the population of FcRn antagonist molecules.

[0218] In some embodiments, the eighth subpopulation makes up less than 7.5%, less than7.0%, 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. In some embodiments, the eighth subpopulation makes up 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 makes up 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 makes up 2.5%-7.5%, 3.0%- 5.0%, or 3.5%-4.5% of the population of FcRn antagonist molecules. In some embodiments, the eighth subpopulation makes up 2.9%-7.4% or 3.0%-6.3% of the population of FcRn antagonist molecules.

[0219] In some embodiments, the ninth subpopulation makes up less than 3.5%, less than3.0%, 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 makes up 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 makes up 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 makes up 0.5%-3.5%, 1.5%-2.0%, or 1.0%-1.5% of the population of FcRn antagonist molecules. In some embodiments, the ninth subpopulation makes up 0.4%-3.2% or 0.5%- 2.6% of the population of FcRn antagonist molecules.

[0220] In some embodiments, the tenth subpopulation makes up less than 2.0%, less than1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some embodiments, the tenth subpopulation makes up 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 makes up 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the tenth subpopulation makes up 0.5%-2.0%, 0.5%-1.5%, or 1.0%-1.5% of the population of FcRn antagonist molecules.

[0221] In some embodiments, the eleventh subpopulation makes up less than 2.0%, less than1.5%, less than 1%, or less than 0.5% of the population of FcRn antagonist molecules. In some 46 BUSINESS.32923153.1embodiments, the eleventh subpopulation makes up about 2.0%, about 1.5%, about 1%, or about 0.5% of the population of FcRn antagonist molecules. In some embodiments, the eleventh subpopulation makes up 2.0%, 1.5%, 1%, or 0.5% of the population of FcRn antagonist molecules. In some embodiments, the eleventh subpopulation makes up 0.5%-2.0%, 0.5%-1.5%, or 1.0%-1.5% of the population of FcRn antagonist molecules.

[0222] In some embodiments, the population of FcRn antagonist molecules comprises one ormore of the FcRn antagonists described herein. In some embodiments, the FcRn antagonist is any of those described in International Patent Application No. PCT / IB2023 / 000696, filed on November 14, 2023, incorporated herein by reference in its entirety. In some embodiments, the FcRn antagonist is a population of FcRn antagonists as described in International Patent Application No. PCT / IB2023 / 000696, filed on November 14, 2023, incorporated herein by reference in its entirety.

[0223] In an embodiment, the FcRn antagonist is efgartigimod (CAS Registry No. 1821402-21-4). Efgartigimod is described in further detail herein below. The term “efgartigimod” as used herein is interchangeable with “efgartigimod alfa”. In some embodiments, efgartigimod is efgartigimod alfa-fcab. Pharmaceutical Compositions

[0224] The instant disclosure provides pharmaceutical compositions comprising an FcRnantagonist.

[0225] In an embodiment, the FcRn antagonist is efgartigimod, or a biosimilar versionthereof. Efgartigimod (ARGX-113) is a modified human immunoglobulin (Ig) gamma (IgG) 1- derived Fc of the za allotype that binds with nanomolar affinity to human FcRn. Efgartigimod encompasses the IgG1 Fc region (encompassing residues of SEQ ID NO: 2) and has been engineered using ABDEG™ technology to increase its affinity for FcRn at both physiological and acidic pH, see Vaccaro C et al., Nat Biotechnol.2005; 23(10):1283. See also U.S. Pat. No.10,316,073, the contents of which are incorporated by reference herein in their entirety. The increased affinity for FcRn of efgartigimod at both acidic and physiological pH results in a blockage of FcRn-mediated recycling of IgGs.

[0226] Efgartigimod alfa is a human recombinant immunoglobulin G1 (IgG1)-derived Fcfragment produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. Efgartigimod alfa is a human IgG1 antibody fragment engineered for increased affinity to the neonatal Fc Receptor (FcRn). 47 BUSINESS.32923153.1

[0227] Efgartigimod alfa-fcab is a human immunoglobulin G1 (IgG1) -derived Fc fragment(fragment, crystallized) of the za allotype. The efgartigimod alfa-fcab Fc fragment is a homodimer consisting of two identical peptide chains each consisting of 227 amino acids linked together by two interchain disulfide bonds with affinity for FcRn. The molecule weight of efgartigimod alfa-fcab is approximately 54 kDa.

[0228] Efgartigimod is a prescription medicine registered as VYVGART®, which isapproved in the United States and in Europe for the treatment of adults with gMG who are anti-AChR antibody positive, and in Japan for the treatment of adults with gMG who do not have sufficient response to steroids or non-steroidal immunosuppressive therapies (ISTs). Efgartigimod is under development for both the intravenous (IV) and subcutaneous (SC) administration route in multiple indications.

[0229] In an embodiment, the pharmaceutical composition is a biological product that ishighly similar to and has no clinically meaningful differences from efgartigimod.

[0230] In some embodiments, the pharmaceutical composition comprises an FcRn antagonistin an amount from about 20 mg to about 4,000 mg. In some embodiments, the pharmaceutical composition comprises an FcRn antagonist in an amount from about 300 mg to about 2,000 mg. In some embodiments, the pharmaceutical composition comprises an FcRn antagonist in an amount from about 500 mg to about 1500 mg.

[0231] In some embodiments, the pharmaceutical composition comprises about 1,000 mg ofan FcRn antagonist. In some embodiments, the pharmaceutical composition comprises 1,000 mg of an FcRn antagonist. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0232] In some embodiments, the pharmaceutical composition comprises about 200 mg / mLof an FcRn antagonist, about 2,000 U / mL of rHuPH20, about 10.5 mg / mL L-arginine hydrochloride, about 1.4 mg / mL L-histidine, about 2.2 mg / mL L-histidine hydrochloride monohydrate, about 1.5 mg / mL L-methionine, about 0.4 mg / mL polysorbate 80, about 4.1 mg / mL sodium chloride, and about 20.5 mg / mL sucrose, at a pH of about 6.0. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0233] In some embodiments, the pharmaceutical composition comprises 200 mg / mL of anFcRn antagonist, 2,000 U / mL of rHuPH20, 10.5 mg / mL L-arginine hydrochloride, 1.4 mg / mL L- histidine, 2.2 mg / mL L-histidine hydrochloride monohydrate, 1.5 mg / mL L-methionine, 0.4 mg / mL 48 BUSINESS.32923153.1polysorbate 80, 4.1 mg / mL sodium chloride, and 20.5 mg / mL sucrose, at a pH of 6.0. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0234] In some embodiments, the pharmaceutical composition comprises 200 mg / mL ofefgartigimod, 2,000 U / mL of rHuPH20, 10.5 mg / mL L-arginine hydrochloride, 1.4 mg / mL L- histidine, 2.2 mg / mL L-histidine hydrochloride monohydrate, 1.5 mg / mL L-methionine, 0.4 mg / mL polysorbate 80, 4.1 mg / mL sodium chloride, and 20.5 mg / mL sucrose, at a pH of 6.0. This is referred to herein as Efgartigimod SC Gen2.

[0235] In some embodiments, the pharmaceutical composition comprises about 200 mg / mLof an FcRn antagonist, about 2,000 U / mL of rHuPH20, about 20 mM L-histidine / L-histidine hydrochloride, about 70 mM sodium chloride, about 50 mM L-arginine hydrochloride, about 60 mM sucrose, about 10 mM L-methionine, and about 0.04% (w / ) polysorbate 80, at a pH of about 6.0. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0236] In some embodiments, the pharmaceutical composition comprises 200 mg / mL of anFcRn antagonist, 2,000 U / mL of rHuPH20, 20 mM L-histidine / L-histidine hydrochloride, 70 mM sodium chloride, 50 mM L-arginine hydrochloride, 60 mM sucrose, 10 mM L-methionine, and 0.04% (w / ) polysorbate 80, at a pH of 6.0. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0237] In some embodiments, the pharmaceutical composition comprises 0.02-0.06% w / vpolysorbate 80.

[0238] In some embodiments, the pH of the pharmaceutical composition is 6.0 ± 0.3.

[0239] In some embodiments, the osmolality of the pharmaceutical composition is from 280-450 mOsmol / kg H2O. In some embodiments, the osmolality of the pharmaceutical composition is from 350-380 mOsmol / kg H2O.

[0240] In some embodiments, the potency of the pharmaceutical composition is from 70-135% activity relative to a reference standard. In some embodiments, potency is measured by competitive binding to FcRn in the presence of human IgG3. In some embodiments, potency is measured by human IgG3 competition ELISA.

[0241] In some embodiments, the pharmaceutical composition comprises ≥55.0% of the mainisoform of the FcRn antagonist, from 10.0-27.0% of acidic isoforms of the FcRn antagonist, and ≤24.0% of basic isoforms of the FcRn antagonist. In some embodiment, charge-related variants are measured using imaged capillary isoelectric focusing (icIEF). 49 BUSINESS.32923153.1

[0242] In some embodiments, the pharmaceutical composition comprises ≥97% full-lengthFcRn antagonist molecules and ≤1.8% total fragments of FcRn antagonist molecules as measured by reducing CE-SDS. In some embodiments, the pharmaceutical composition comprises ≥95% full- length FcRn antagonist molecules and ≤2.2% total fragments of FcRn antagonist molecules as measured by non-reducing CE-SDS.

[0243] In some embodiments, the pharmaceutical composition comprises ≥97.0% monomericFcRn antagonist molecules and ≤3.0% aggregates of FcRn antagonist molecules. In some embodiments, monomers and aggregates are measured using GP-HPLC.

[0244] In some embodiments, the pharmaceutical composition is sterile and comprises ≤3.60EU / mL endotoxin. In some embodiments, endotoxin levels are measured using a Limulus amebocyte lysate method.

[0245] In any of the above embodiments, the pharmaceutical composition may be a unitdosage form.

[0246] In an embodiment, the unit dosage form comprises the FcRn antagonist as a dryformulation for dissolution such as a lyophilized powder, freeze-dried powder, or water-free concentrate. In an embodiment, the dry formulation is comprised in a hermetically sealed container such as a vial, an ampoule, or a sachet.

[0247] In an embodiment, the unit dosage form comprises the FcRn antagonist as a liquidformulation, e.g., injection solution. In an embodiment, the liquid formulation is comprised in a hermetically sealed container such as a vial, a sachet, a pre-filled syringe, a pre-filled autoinjector, or a cartridge for a reusable syringe or applicator. In an embodiment, the liquid formulation is comprised in a single-dose vial.

[0248] In some embodiments, the dosage form is overfilled to allow withdrawal of a givenamount of formulation. In some embodiments, the dosage form is a single-dose vial that contains at least 5.6 mL of a liquid formulation comprising an FcRn antagonist at a concentration of 200 mg / mL. In some embodiments the vial is overfilled. In some embodiments, the overfilled vial comprises 5.6- 6.9, 5.6-6.5, 5.6-6.0, or 5.6-5.8 mL of liquid formulation. In some embodiments, the overfilled vial comprises about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, or about 6.9 mL of liquid formulation. In some embodiments, the overfilled vial comprises 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, or 6.9 mL of liquid formulation. In some embodiments, the overfilled vial comprises about 5.8 mL of liquid formulation. In some embodiments, the overfilled vial comprises 5.8 mL of liquid formulation. 50 BUSINESS.32923153.1In some embodiments, the liquid formulation comprises efgartigimod, or a biosimilar version thereof. In some embodiments, the liquid formulation comprises efgartigimod and rHuPH20.

[0249] In an embodiment, the single-dose vial may contain 5.6 mL of a liquid formulationcomprising an FcRn antagonist in an amount of 1,120 mg. In some embodiments, the single-dose vial is overfilled to allow withdrawal of 5.6 mL or more of the liquid formulation from the vial. In some embodiments, the single-dose vial is overfilled by 2-5%. In some embodiments, the single-dose vial is overfilled by 3%. In some embodiments, the single-dose vial contains 5.8 mL of a liquid formulation comprising an FcRn antagonist in an amount of 1,154 mg. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0250] In some embodiments, the single-dose vial contains 5.6 mL of a liquid formulationcomprising 1,120 mg of an FcRn antagonist, and 11,200 Units of rHuPH20. Each mL of vial solution contains 200 mg of efgartigimod alfa, 2,000 units of hyaluronidase (human recombinant) and histidine (1.4 mg), L-histidine hydrochloride monohydrate (2.2 mg), methionine (1.5 mg), polysorbate 20 (0.4 mg), sodium chloride (5.8 mg), sucrose (20.5 mg), and water for injection, USP, at a pH of 6.0. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0251] In an embodiment, the single-dose vial may contain 5.0 mL of a liquid formulationcomprising an FcRn antagonist in an amount of 1,000 mg. In some embodiments, the single-dose vial is overfilled to allow withdrawal of 5.0 mL or more of the liquid formulation from the vial. In some embodiments, the single-dose vial is overfilled by 2-5%. In some embodiments, the single-dose vial is overfilled by 3%. In some embodiments, the single-dose vial contains 5.15 mL of a liquid formulation comprising an FcRn antagonist in an amount of 1,030 mg. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0252] In some embodiments, the liquid formulation has a viscosity of 8-14 mPa s. In someembodiments, the liquid formulation has a viscosity of 8-13 mPa s, 9-12 mPa s, 10-11 mPa s or 11- 12 mPa s. In some embodiments, the liquid formulation has a viscosity of about 8 mPa s, about 9 mPa s, about 10 mPa s, about 11 mPa s, about 12 mPa s, about 13 mPa s, or about 14 mPa s.

[0253] In some embodiments, the maintenance of the ranges of viscosities allows the liquidformulation to be rapidly injected at room temperature. Unexpectedly, injection times of less than 30 seconds with the liquid formulations provided herein are associated with lower incidence of injection site reactions. In some embodiments, the injection is performed in less than 10, 15, 18, 20, 25, 28, 30, 32, or 35 seconds. In some embodiments, the injection is performed in 10-35, 15-32, 20-30, or 25-28 51 BUSINESS.32923153.1seconds. In some embodiments, the injection is performed in about 10, about 15, about 18, about 20, about 25, about 28, about 30, about 32, or about 35 seconds. In some embodiments, the injection is performed in 10, 15, 18, 20, 25, 28, 30, 32, or 35 seconds. In some embodiments, the injection is performed in less than 30 seconds. In some embodiments, the injection is performed in 30 seconds or less. In some embodiments, the injection is performed in 20-30, 20-28, or 20-25 seconds. In some embodiments, the injection is performed in about 20-30 seconds. In some embodiments, the injection is performed in 20-30 seconds. In some embodiments, during the time the plunger is pressed the liquid pharmaceutical composition is at 20˚ C - 30˚ C.

[0254] In some embodiments, the single-dose vial contains 5.0 mL of a liquid formulationcomprising 1,000 mg of an FcRn antagonist, and 10,000 Units of rHuPH20. Each mL of vial solution contains 200 mg of efgartigimod alfa, 2,000 units of hyaluronidase (human recombinant) and histidine (1.4 mg), L-histidine hydrochloride monohydrate (2.2 mg), methionine (1.5 mg), polysorbate 20 (0.4 mg), sodium chloride (5.8 mg), sucrose (20.5 mg), and water for injection, USP, at a pH of 6.0. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0255] In some embodiments, the dosage form is overfilled to allow withdrawal of a givenamount of formulation. In some embodiments, the dosage form is a single-dose pre-filled syringe that contains at least 5.6 mL of a liquid formulation comprising an FcRn antagonist at a concentration of 200 mg / mL. In some embodiments the pre-filled syringe is overfilled. In some embodiments, the overfilled pre-filled syringe comprises 5.0-6.9, 5.0-6.5, 5.0-5.5, or 5.0-5.2 mL of liquid formulation. In some embodiments, the overfilled pre-filled syringe comprises about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, or about 6.9 mL of liquid formulation. In some embodiments, the overfilled pre-filled syringe comprises 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, or 6.9 mL of liquid formulation. In some embodiments, the overfilled pre-filled syringe comprises about 5.2 mL of liquid formulation. In some embodiments, the overfilled pre-filled syringe comprises 5.2 mL of liquid formulation. In some embodiments, the liquid formulation comprises efgartigimod, or a biosimilar version thereof. In some embodiments, the liquid formulation comprises efgartigimod and rHuPH20.

[0256] In an embodiment, the single-dose pre-filled syringe may contain 5.0 mL of a liquidformulation comprising an FcRn antagonist in an amount of 1,000 mg. In some embodiments, the single-dose pre-filled syringe is overfilled to allow withdrawal of 5.0 mL or more of the liquid 52 BUSINESS.32923153.1formulation from the pre-filled syringe. In some embodiments, the single-dose pre-filled syringe is overfilled by 2-5%. In some embodiments, the single-dose pre-filled syringe is overfilled by 3%. In some embodiments, the single-dose pre-filled syringe contains 5.2 mL of a liquid formulation comprising an FcRn antagonist in an amount of 1,030 mg. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0257] In some embodiments, the single-dose pre-filled syringe contains 5.0 mL of a liquidformulation comprising 1,000 mg of an FcRn antagonist, and 10,000 Units of rHuPH20. Each mL of pre-filled syringe solution contains 200 mg of efgartigimod alfa, 2,000 units of hyaluronidase (human recombinant) and histidine (1.4 mg), L-histidine hydrochloride monohydrate (2.2 mg), methionine (1.5 mg), polysorbate 20 (0.4 mg), sodium chloride (5.8 mg), sucrose (20.5 mg), and water for injection, USP, at a pH of 6.0. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0258] In some embodiments, the pharmaceutical composition has a shelf-life of 12 monthswhen stored at 2℃-8℃. In some embodiments, the pharmaceutical composition has a shelf-life of up to 12 months when stored at 2℃-8℃. In some embodiments, the pharmaceutical composition has a shelf-life of 12 months when stored at 20℃-25℃. In some embodiments, the pharmaceutical composition has a shelf-life of up to 12 months when stored at 20℃-25℃.

[0259] In some embodiments, the pharmaceutical compositions described herein arecontraindicated in patients with serious hypersensitivity to the FcRn antagonist (e.g., efgartigimod) or to any of the excipients in the compositions. In some embodiments, the hypersensitivity is anaphylaxis and / or hypotension leading to syncope. Kits

[0260] The present disclosure provides kits comprising the pre-filled syringes describedherein as well as their packaging. In some embodiments, needles are provided in separate packaging. In some embodiments, the kits further comprise a label. In some embodiments, the label further comprises instructions for use of the pre-filled syringes in the kits.

[0261] In some embodiments, each pre-filled syringe is provided in a container of 1-20 or 2-10 pre-filled syringes. In some embodiments, each container contains 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 pre-filled syringes. In some embodiments, each pre-filled syringe is comprised in a separate sealed wrapper. In some embodiments, the separate sealed wrapper is sterile. 53 BUSINESS.32923153.1In some embodiments, each container contains at least one copy of instructions for use of the pre- filled syringes.

[0262] In some embodiments, the instructions are provided on a label. In some embodiments,the instructions are provided independent of a label. In some embodiments, the instructions provide information needed before the pre-filled syringe is used. In some embodiments, the information provides that the prefilled syringe is for single-dose use only and cannot be reused. In some embodiments, the information provides that the prefilled syringe should not be used if it has been at room temperature for longer than 4 hours. In some embodiments, the information provides that the prefilled syringe should not be used if it has expired. In some embodiments, the information provides that the prefilled syringe should not be used if it has been damaged. In some embodiments, the information provides that damaged pre-filled syringes should be returned to the pharmacy. In some embodiments, the information provides that the prefilled syringe should not be used if the medicine (e.g., efgartigimod and rHuPH20) is discolored or contains particles. In some embodiments, the information provides that the medicine should look clear to light yellow in color. A little cloudiness is normal. In some embodiments, the information provides that the prefilled syringe should not be used if it has been frozen. In some embodiments, the information provides that the prefilled syringe should not be used if it was stored in direct sunlight.

[0263] In some embodiments, the instructions provide information regarding storage of thepre-filled syringe. In some embodiments, the information provides that the pre-filled syringe should be stored in the refrigerator between 36°F to 46°F (2°C to 8°C). In some embodiments, the information provides that the pre-filled syringes in the original carton to protect them from light. In some embodiments, the information provides that the pre-filled syringes should be kept out of the reach of children. In some embodiments, the information provides that the pre-filled syringes should not be frozen. In some embodiments, the information provides that the pre-filled syringes should not be stored in direct sunlight. In some embodiments, each carton contains 1 or 4 pre-filled syringes.

[0264] In some embodiments, the instructions provide a schematic of the parts of the pre-filled syringe. An example of such a schematic is provided in FIG.1. In some embodiments, the pre- filled syringe and needle shown in FIG.1 are provided separately. In some embodiments, the needle is a safety needle. In some embodiments, the needle is 25G. In some embodiments, the needle is 5 / 8” in length. In some embodiments, the needle is thin wall. In some embodiments, the needle is regular wall. 54 BUSINESS.32923153.1

[0265] FIG. 1 shows an example of a syringe 100 and needle assembly 400. The syringe 100and needle assembly 400 may be used in combination with one another, but also other needle assemblies may be used with the syringe 100. Generally, this syringe 100 may be used as shown throughout the other Figures, but again other syringes than shown in FIG.1 can be used as shown throughout the Figures. The syringe 100 and / or needle assembly 400 may incorporate any of the modifications, embodiments and / or examples discussed herein.

[0266] The syringe 100 is formed of a syringe body 10. This syringe body 10 has a barrel withan interior volume. The barrel can be defined as a hollow generally cylindrical section, defining this interior volume. The barrel extends between a proximal end and a distal end, defining an axial direction therebetween. These can equally be defined as the distal and proximal end of the syringe body 10. The interior volume is defined between a wall of the barrel, the proximal end and the distal end. In general, throughout the distal end of a component may be end nearer an injection site in use.

[0267] The syringe body 10 may comprise a flange 12 (identified as finger flange 12 in FIG.1). By flange, this means a portion of the syringe body 10 which extends radially outward from its axial centre. In use, a user may pull on this flange 12 with their index finger and middle finger (or any other two fingers).

[0268] This finger flange 12 can also be identified as one or more protrusions – particularly apair of protrusions (or flaps). This pair may be opposite to one another about an outer circumference of the barrel.

[0269] In certain cases, the protrusions may be continuous with each other. That is, there maybe at least some protrusion around an entire outer circumference of the barrel. This protrusion extending all around the circumference may have a varying length about the outer circumference of the barrel. The length of the protrusion defined as the distance the protrusion extends from the outer circumference of the barrel. There may be a pair of regions with maximum length, which may be arranged opposite to one another about the outer circumference of the barrel.

[0270] A plunger 20 is provided, at least partially disposed within the interior volume of thebarrel. As shown in FIG. 1, a distal end of the plunger 20 may be within the interior volume of the barrel and a proximal end of the plunger 20 may be external to the interior volume of the barrel. The plunger 20 fluidically seals with an inner wall of the syringe body 10. For example, FIG. 1 shows how a stopper 24 (such as the gray stopper 24) can be provided. This will generally be formed of a material suitable for forming a fluidic seal such as an elastomeric member. The stopper 24 helps inhibit back leakage, as discussed herein. 55 BUSINESS.32923153.1

[0271] The plunger 20 may have a flange 22 at its proximal end, for a user to press on. Thisis identified as a thumb pad 22 in FIG. 1. By flange, this means a portion of the plunger 20 which extends radially outward from its axial centre. In use, the user may depress the plunger by applying a force to the proximal end (for example the thumb pad 22 where present) with their thumb.

[0272] At the distal end of the syringe body 10 a nozzle is provided. In FIG. 1, this nozzle iscovered by the syringe cap 32 and collar 30 discussed more below. The nozzle represents a section of the syringe 10 with a smaller diameter than the barrel. In use, a needle 40 is attachable to the nozzle. For example, the nozzle may have an attachment mechanism such as a thread, one or more clips, interference sections, or the like, for attaching the needle 40 to the syringe body 10. In use, this puts the needle 40 in fluid communication with the interior volume of the syringe body 10.

[0273] A liquid 2 is provided in the interior volume of the syringe 100, between the plunger20 and the nozzle. This can be defined as an extractable volume (or a working volume) for the syringe 100. The extractable volume may be 4.0-6.0 mL, optionally 4.3-5.7 mL, optionally 4.5-5.5 mL, or optionally about 5.0 mL, or 5.0 mL. The nozzle itself may have an interior volume of 0.1 mL to 0.3 mL, such as about or exactly 2.0 mL.

[0274] The liquid 2 may be referred to as a liquid medicine 2 such as shown in FIG. 1. Thisliquid 2 may be FcRn antagonist and hyaluronidase, for example as discussed herein. The liquid 2 may be any of the embodiments or examples discussed herein. The syringe 100 may be referred to as a prefilled syringe 100 as it is supplied with this liquid 2 inside the syringe 100. In other words, it has been filled previously to being provided.

[0275] A syringe cap 32 may be provided to seal the nozzle of the syringe 100. This syringecap can be detachably attached to a collar 30 which surrounds the nozzle. For example, this could be a textured collar 30. The syringe cap 32 is detached from the collar 30, such as by snapping a frangible connection therebetween. This then exposes the nozzle for use of the syringe 100. The collar 30 may comprise an attachment (such as a thread, one or more clips, interference sections, or the like) for attaching the needle 40 to the syringe body 10.

[0276] In use, the plunger 20 is depressed such that the distal end of the plunger movestowards the distal end of the syringe body 10. This thereby reduces the size of the extractable volume, which forces the liquid 2 out of the syringe 100 via the nozzle. When the needle 40 is attached to the nozzle, the liquid 2 is forced out through the needle 40. For example, this could be into a patient.

[0277] The needle assembly 400 (which can also be referred to as a needle) shown in FIG. 1comprises a needle 40 (in that it is the sharp element which punctures the patient’s skin). This needle 56 BUSINESS.32923153.140 is provided with a needle cap 42. The needle cap 42 covers the needle 40, for preventing the needle 40 being damaged, losing sterility, or being inserted inadvertently prior to injection. The needle cap 42 may be transparent or translucent (or clear).

[0278] The needle 40 is further provided with a needle shield 44. The needle shield 44 isformed as a flange or flap extending from a proximal base of the needle 40. This needle shield 44 is hinged to the proximal base. As shown in FIG. 1, the needle shield 44 is initially spaced from the needle 40 such that the needle 40 can be used for an injection. After use, the needle shield 44 is pivoted to cover the needle 40 to prevent the needle 40 from inadvertently piercing anything else. Prior to use, the needle shield 44 may be pivoted away from the needle cap 42 for removal of the needle cap 42. One or more catches may be provided to hold the needle shield 44 in its various positions.

[0279] In use, the syringe cap 32 (where present) is removed. The needle cap 42 (wherepresent) is removed from the needle 40. The needle 40 is then attached to the syringe 100. The needle 40 pierces into a patient’s skin (or other area for injection). The plunger 40 is depressed to expel the liquid 2 through the needle 40. The needle 40 is then removed from the patient’s skin (or other area for injection). The needle shield 44 is then pivoted to cover the needle 40. Further operation before and after these steps may be as discussed herein.

[0280] In some embodiments, the instructions provide information for gathering and checkingsupplies. In some embodiments, the information provides steps for removing the carton containing the pre-filled syringes from the container. In some embodiments, these steps include removing the pre-filled syringe carton from the refrigerator and removing one pre-filled syringe from the carton. The remaining pre-filled syringes are placed back in the refrigerator for later use. The pre-filled syringe is removed from its individual packaging (e.g., a tray).

[0281] In some embodiments, the information provides steps for checking the pre-filledsyringe before use. In some embodiments, these steps include checking the expiration date on the pre- filled syringe label and not using the pre-filled syringe if the expiration date has passed. Steps includechecking the condition of the pre-filled syringe and the prefilled syringe cap and not using the pre-filled syringe if it is cracked, broken, damaged, or if the cap is missing. Steps also include checking the appearance of the medicine in the pre-filled syringe. The medicine should look clear to light yellow in color. A little cloudiness is normal. The pre-filled syringe should not be used if the medicine is discolored or contains particles. 57 BUSINESS.32923153.1

[0282] In some embodiments, the instructions provide information for preparing for theinjection. In some embodiments, the information provides steps for allowing the pre-filled syringe to warm to room temperature. In some embodiments, the steps include placing the prefilled syringe on a clean flat surface and let it sit for at least 30 minutes, to allow it to warm to room temperature. The pre-filled syringe should not be warmed in any other way. The pre-filled syringe should not be used if it has been at room temperature for longer than 4 hours.

[0283] In some embodiments, the information provides steps for gathering supplies andwashing hands. In some embodiments, the steps include gathering a safety needle, alcohol swab, sharps disposal container, sterile gauze and / or bandage (as needed). These supplies are not provided with the pre-filled syringe. The steps also include the subject washing their hands.

[0284] In some embodiments, the information provides steps for snapping off the syringe capand attaching a needle. The steps include carefully opening the needle package and removing the needle (see FIG.2A) and throwing away the packaging into household trash. The steps also include bending the syringe cap to one side to snap it off and remove it from the prefilled syringe (see FIG. 2B) and throwing away the syringe cap. The tip of the pre-filled syringe should not be touched after the cap has been removed. The steps also include holding the pre-filled syringe in one hand andattaching the needle to the pre-filled syringe by twisting it on (clockwise / to the right) until resistanceis felt (see FIG.2C). The needle would then be attached to the prefilled syringe (see FIG.2D).

[0285] In some embodiments, the information provides steps for choosing and cleaning theinjection site on the abdomen. In some embodiments, the steps include choosing an injection site on the abdomen (belly area) at least two inches away from the belly button (navel) (see FIG.3A). The injection site should be rotated (i.e. changed) for each injection. The injection should not be performed on skin that is irritated, red, bruised, infected, or scarred. The injection should not be performed into a vein. The formulation is for subcutaneous (under the skin) injection only. The steps also include cleaning the chosen injection site with an alcohol swab and letting it air dry. The injection site should not be blown on or touched after it has been cleaned.

[0286] In some embodiments, the instructions provide information for injecting the liquidpharmaceutical composition in the pre-filled syringe. In some embodiments, the information provides steps for pulling back the needle shield and removing the needle cap. In some embodiments, the steps include pulling the needle shield back (see FIG.3B). In some embodiments, the needle shield will be used after the injection to cover the needle and protect from needle-stick injuries. The steps includeholding the prefilled syringe body and removing the clear needle cap by pulling it straight off of the58 BUSINESS.32923153.1needle (see FIG.3C). The steps also include throwing away the needle cap into household trash. The needle cap should not be put back onto the needle.

[0287] In some embodiments, the information provides steps for giving the injection. In someembodiments, the steps include pinching the cleaned injection site and, while pinching the skin, inserting the needle at a 45˚ to 90˚ angle to the surface of the injection site all the way into the pinched skin (see FIG.4A). The pinched skin is then released. The skin should not be pinched so tightly as it causes bruising. The steps also include slowly pressing the plunger down all the way until it stops to inject the medicine (see FIG.4B). The steps also include taking at least 20-30 seconds to inject all of the liquid pharmaceutical composition. In some embodiments, the information provides that resistance will be felt as the plunger is pressed down. In case of discomfort, the injection should be performed more slowly. The injection can be paused if the grip needs to be changed during the injection. The plunger should not be forced down quickly as this will make the plunger harder topress. The steps also include removing the needle from the skin by pulling it out straight out withoutchanging from the angle of insertion of the needle (see FIG.4C) after all the liquid pharmaceutical composition has been injected.

[0288] In some embodiments, the instructions provide information for disposing of the usedpre-filled syringe. In some embodiments, the information provides steps for covering the needle and throwing away the used pre-filled syringe. In some embodiments, the steps include carefully pushing the needle shield over the needle until it snaps into place and covering the needle (see FIG.5A). This helps to prevent needle-stick injuries. The needle is not recapped using the needle cap; only use the needle shield is used to cover the needle. The steps also include throwing away the used pre-filled syringe, with the needle still attached, into an FDA-cleared sharps disposal container right away after use (see FIG.5B). Loose needles and syringes should not be disposed of in your household trash. In some embodiments, the information provides steps for treating the injection site. If there is a small amount of blood or liquid at the injection site, a gauze is pressed over the injection site until the bleeding stops and a small adhesive bandage may be applied if needed.

[0289] In some embodiments, the label includes an indication for the treatment of gMG inadult patients who are anti-AChR antibody positive. In some embodiments, the label includes an indication for the treatment of adults with gMG who do not have sufficient response to steroids or non-steroidal immunosuppressive therapies (ISTs). In some embodiments, the label includes data demonstrating an MG-ADL response rate of 67.7% and a QMG response rate of 63.1% in a population of gMG patients who received 10 mg / kg efgartigimod, compared to a MG-ADL response 59 BUSINESS.32923153.1rate of 29.7% and a QMG response rate of 14.1% in a population of gMG patients who received placebo. Methods

[0290] The present disclosure provides methods of reducing serum IgG levels in a subject inneed thereof comprising administering to the subject an effective amount of an FcRn antagonist according to the disclosure or a pharmaceutical composition comprising the same. The disclosure also provides methods for treating an antibody-mediated disorder (e.g., an autoantibody-mediated disorder) in a subject comprising administering to the subject an effective of an FcRn antagonist according to the disclosure or a pharmaceutical composition comprising the same. In some embodiments, the antibody-mediated disorder is an autoimmune disease. In some embodiments, the autoimmune disease is myasthenia gravis (e.g., gMG).

[0291] Approximately 80% of all MG patients, but only about 50% of ocular MG (oMG)patients, test positive for the presence of anti-AChR autoantibodies (i.e., are anti-AChR antibody positive). AChR autoantibodies can be measured using one or more art-recognized methods, including radioimmunoprecipitation and cell-based assays (see Jacob et al., Arch. Neurol., 2012; 69:994-1001), as well as ELISA and fluorescence assays based on immunoprecipitation (see Yang et al., J Neurol. Sci., 2011; 301:71-76). In some embodiments, the subject has gMG and is anti-AChR antibody positive. In some embodiments, the subject has gMG and is anti-AChR antibody negative. In some embodiments, the subject has gMG and does not have sufficient response to steroids or non- steroidal immunosuppressive therapies as determined by a health care provider.

[0292] The present disclosure provides methods of subcutaneously administering an FcRnantagonist in a pre-filled syringe. In some embodiments, the pre-filled syringe is stored in a refrigerator. In some embodiments, the pre-filled syringe is stored at a temperature of 2˚ C - 8˚ C. In some embodiments, the pre-filled syringe is stored at a temperature of about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10˚ C. In some embodiments, the pre-filled syringe is stored at a temperature of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10˚ C. In some embodiments, the pre- filled syringe is stored for 30-180, 60-120, or 80-100 days.

[0293] In some embodiments, the pre-filled syringe is warmed to room temperature beforebeing administered to a subject. In some embodiments, the pre-filled syringe is warmed to 20˚ C - 30˚ C before being administered to a subject. In some embodiments, the pre-filled syringe is warmed to 60 BUSINESS.32923153.1about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, or about 30˚ C before being administered to a subject. In some embodiments, the pre-filled syringe is warmed to 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30˚ C before being administered to a subject.

[0294] In some embodiments, the pre-filled syringe is warmed for at least 15-60 minutes. Insome embodiments, the pre-filled syringe is warmed for at least 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 minutes. In some embodiments, the pre-filled syringe is warmed for about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, or about 60 minutes. In some embodiments, the pre-filled syringe is warmed for 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 minutes. In some embodiments, the pre-filled syringe is warmed for 20-55, 25-50, or 30-45 minutes. In some embodiments, the pre-filled syringe is warmed for at least 30 minutes. In some embodiments, the pre- filled syringe is warmed for about 30 minutes. In some embodiments, the pre-filled syringe is warmed for 30 minutes.

[0295] In some embodiments, the pre-filled syringe is stored at room temperature. In someembodiments, the pre-filled syringe is stored at 20˚ C - 30˚ C. In some embodiments, the pre-filled syringe is stored at about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, or about 30˚ C. In some embodiments, the pre-filled syringe is stored at 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30˚ C. In some embodiments, the pre-filled syringe is stored for up to 1 month at 20° C to 25° C. In some embodiments, the pre-filled syringe is stored for up to 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 or 30 days at 20° C to 25° C. In some embodiments, the pre-filled syringe is stored for up to 3 days at 20° C to 25° C. In some embodiments, the pre-filled syringe is stored for up to 1 month up to 30° C. In some embodiments, the pre-filled syringe is stored for up to 30 days up to 30° C. In some embodiments, the pre-filled syringe is stored for a single period of up to 30 days or 1 month at room temperature up to 30° C. In some embodiments, the pre-filled syringe is stored in its original container. In some embodiments, the pre-filled syringe should not be frozen when stored. In some embodiments, the pre-filled syringe should not be shaken when stored.

[0296] In some embodiments, a needle is attached to the pre-filled syringe. In someembodiments, the needle includes a needle cap. In some embodiments, the needle includes a needle shield. In some embodiments, the needle is provided in separate packaging from the pre-filled syringe. In some embodiments, the needle is snapped onto the pre-filled syringe. In some embodiments, the needle is screwed onto the pre-filled syringe. In some embodiments, the needle shield is disengaged before removal of the needle cap. 61 BUSINESS.32923153.1

[0297] In some embodiments, the injection site is chosen on the abdomen of the subject. Insome embodiments, the injection site is within 2-4 inches of the navel of the subject. In some embodiments, the injection site is within 2-3 inches of the navel of the subject. In some embodiments, the injection site is within about 0.5, about 1.0, about 1.5, about 2.0, about 2.5, about 3.0, about 3.5, or about 4.0 inches of the navel of the subject. In some embodiments, the injection site is within 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, or 4.0 inches of the navel of the subject.

[0298] In some embodiments, the injection site is pinched prior to injection. In someembodiments, the injection site is pinched until the injection site is injected with the needle. In some embodiments, the pinch on the injection site is released after the injection occurs. In some embodiments, the pinch on the injection site is released after the injection occurs but before the needle is removed. In some embodiments, the pinch on the injection site is released after the injection occurs but before the needle is removed. In some embodiments, the pinching of the injection site is performed as shown in FIGs.4A and 4B.

[0299] In some embodiments, the needle is inserted into the injection site. In someembodiments, the needle is inserted into the injection site while it is pinched. In some embodiments, the needle is inserted into the injection site at a 45˚-90˚ angle to the surface of the injection site.

[0300] In some embodiments, after the needle is inserted into the injection site the plunger onthe pre-filled syringe is pressed to inject the liquid pharmaceutical composition. In some embodiments, the plunger is pressed until it stops. In some embodiments, the plunger stops when the distal end of the plunger reaches the distal end of the barrel. In some embodiments, the plunger stops when the stopper at the distal end of the plunger reaches the distal end of the barrel. In some embodiments, the plunger stops when the thumb pad comes within 1 cm of the proximal end of the barrel of the pre-filled syringe.

[0301] In some embodiments, the plunger is pressed for less than 10, 15, 18, 20, 25, 28, 30,32, or 35 seconds. In some embodiments, the plunger is pressed for 10-35, 15-32, 20-30, or 25-28 seconds. In some embodiments, the plunger is pressed for about 10, about 15, about 18, about 20, about 25, about 28, about 30, about 32, or about 35 seconds. In some embodiments, the plunger is pressed for 10, 15, 18, 20, 25, 28, 30, 32, or 35 seconds. In some embodiments, the plunger is pressed for less than 30 seconds. In some embodiments, the plunger is pressed for 20-30, 20-28, or 20-25 seconds. In some embodiments, the plunger is pressed for about 20-30 seconds. In some embodiments, the plunger is pressed for 20-30 seconds. In some embodiments, during the time the plunger is pressed it is pressed until it stops. In some embodiments, during the time the plunger is 62 BUSINESS.32923153.1pressed the liquid pharmaceutical composition is at room temperature. In some embodiments, during the time the plunger is pressed the liquid pharmaceutical composition is at 20˚ C - 30˚ C.

[0302] In some embodiments, after the injection has occurred the needle is removed from thechosen site. In some embodiments, the needle is removed straight out from the injection site. In some embodiments, the needle is removed at the same angle at which it was inserted. In some embodiments, the needle is removed within a 5˚ angle from which it was inserted.

[0303] In some embodiments, the needle is covered after the needle is removed from thesubject. In some embodiments, the needle is covered by a needle shield. In some embodiments, the needle shield was associated with the needle before the needle was attached to the pre-filled syringe. In some embodiments, gauze is applied to the chosen site after removing the needle.

[0304] In some embodiments, the subject shows reduction in erythema at the injection site inless than 30, 45, 60, 75, or 90 minutes. In some embodiments, the subject shows reduction in swelling at the injection site in less than 30, 45, 60, 75, or 90 minutes. In some embodiments, the subject shows reduction in induration at the injection site in less than 30, 45, 60, 75, or 90 minutes. In some embodiments, the subject indicates no pain or mild pain immediately after the injection. In some embodiments, the subject indicates no pain or mild pain 5 or 10 minutes after the injection. In some embodiments, the subject indicates that they would have the injection again.

[0305] In some embodiments, leakage from the injection is minimal. In some embodiments,leakage from the injection is less than 25, 20, 15, 10, 8, or 5 μL. In some embodiments, back leakage from the injection is minimal. In some embodiments, back leakage from the injection is less than 15, 10, 8, or 5 μL.

[0306] In some embodiments, the administration is performed by the subject on themselves.In some embodiments, the administration is performed by a caregiver to the subject. In some embodiments, the administration is performed by a healthcare professional to the subject. Dosing

[0307] In some embodiments, the FcRn antagonist is administered at a fixed dose of about 20mg to about 20,000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 200 mg to about 20,000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 300 mg to about 6000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 750 mg to about 3000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 1000 mg to about 2500 mg. In some embodiments, 63 BUSINESS.32923153.1the FcRn antagonist is administered at a fixed dose of about 1000 mg to about 2000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of about 1000 mg. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0308] In some embodiments, the FcRn antagonist is administered at a fixed dose of 20 mgto 20,000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 200 mg to 20,000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 300 mg to 6000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 750 mg to 3000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 1000 mg to 2500 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 1000 mg to 2000 mg. In some embodiments, the FcRn antagonist is administered at a fixed dose of 1000 mg. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0309] In some embodiments, the FcRn antagonist is administered at a fixed dose of about 20mg, about 50 mg, about 100 mg, about 200 mg, about 250 mg, about 300 mg, about 500 mg, about 750 mg, about 1000 mg, about 1200 mg, about 1500 mg, about 2000 mg, about 2500 mg, about 3000 mg, about 4000 mg, about 5000 mg, about 6000 mg, about 7000 mg, about 8000 mg, about 9000 mg, about 10,000 mg, about 11,000 mg, about 12,000 mg, about 13,000 mg, about 14,000 mg, about 15,000 mg, about 16,000 mg, about 17,000 mg, about 18,000 mg, about 19,000 mg, or about 20,000 mg. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0310] In some embodiments, the FcRn antagonist is administered at a fixed dose of 20 mg,50 mg, 100 mg, 200 mg, 250 mg, 300 mg, 500 mg, 750 mg, 1000 mg, 1200 mg, 1500 mg, 2000 mg, 2500 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 7000 mg, 8000 mg, 9000 mg, 10,000 mg, 11,000 mg, 12,000 mg, 13,000 mg, 14,000 mg, 15,000 mg, 16,000 mg, 17,000 mg, 18,000 mg, 19,000 mg, or 20,000 mg. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0311] In some embodiments, the FcRn antagonist is administered at a dose of about 0.2mg / kg to about 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 2 mg / kg to about 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 2 mg / kg to about 120 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 3 mg / kg to about 60 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 10 mg / kg to about 25 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof. 64 BUSINESS.32923153.1

[0312] In some embodiments, the FcRn antagonist is administered at a dose of 0.2 mg / kg to200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of about 2 mg / kg to about 200 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of 2 mg / kg to 120 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of 3 mg / kg to 60 mg / kg. In some embodiments, the FcRn antagonist is administered at a dose of 10 mg / kg to 25 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0313] In some embodiments, the FcRn antagonist is administered at a dose of about 0.2mg / kg, about 0.5 mg / kg, about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 12.5 mg / kg, about 15 mg / kg, about 17.5 mg / kg, about 20 mg / kg, about 25 mg / kg, about 30 mg / kg, about 35 mg / kg, about 40 mg / kg, about 45 mg / kg, about 50 mg / kg, about 55 mg / kg, about 60 mg / kg, about 65 mg / kg, about 70 mg / kg, about 75 mg / kg, about 80 mg / kg, about 85 mg / kg, about 90 mg / kg, about 95 mg / kg, about 100 mg / kg, about 110 mg / kg, about 120 mg / kg, about 130 mg / kg, about 140 mg / kg, about 150 mg / kg, about 160 mg / kg, about 170 mg / kg, about 180 mg / kg, about 190 mg / kg, or about 200 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0314] In some embodiments, the FcRn antagonist is administered at a dose of 0.2 mg / kg, 0.5mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, 100 mg / kg, 110 mg / kg, 120 mg / kg, 130 mg / kg, 140 mg / kg, 150 mg / kg, 160 mg / kg, 170 mg / kg, 180 mg / kg, 190 mg / kg, or 200 mg / kg. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0315] In some embodiments, the FcRn antagonist is administered subcutaneously. In someembodiments, the FcRn antagonist is administered subcutaneously once weekly, once every 2 weeks, once every 3 weeks, once every 4 weeks, once monthly, or once every 6 weeks. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0316] In some embodiments, the FcRn antagonist is administered subcutaneously at fixeddose of 100 mg to 10,000 mg once weekly, once every 2 weeks, once every 3 weeks, once every 4 weeks, once monthly, or once every 6 weeks. In some embodiments, the FcRn antagonist is administered subcutaneously at fixed dose of 1000 mg or 2000 mg once weekly, once every 2 weeks, once every 3 weeks, once every 4 weeks, once monthly, or once every 6 weeks. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof. 65 BUSINESS.32923153.1

[0317] In some embodiments, the FcRn antagonist is administered using a phased dosingschedule comprising multiple treatment cycles. In some embodiments, the phased dosing schedule comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, or more treatment cycles. In some embodiments, each treatment cycle independently comprises or consists of administration of 1-5 doses of the FcRn antagonist within 1 month. In some embodiments, at least one treatment cycle comprises or consists of weekly administration of the FcRn antagonist for 4 weeks. In some embodiments, each treatment cycle comprises or consists of weekly administration of the FcRn antagonist for 4 weeks. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0318] In some embodiments, the phased dosing schedule comprises a first treatment cycleand one or more subsequent treatment cycles. In some embodiments, the first treatment cycle and the one or more treatment cycles each independently comprise or consist of administration of 1-5 doses of the FcRn antagonist within 1 month. In some embodiments, the first treatment cycle comprises or consists of weekly administration of the FcRn antagonist for 4 weeks. In some embodiments, at least one of the one or more subsequent treatment cycles comprises or consists of weekly administration of the FcRn antagonist for 4 weeks. In some embodiments, each of the one or more subsequent treatment cycles comprise or consist of weekly administration of the FcRn antagonist for 4 weeks. In some embodiments, each of the one or more subsequent treatment cycles is administered to the subject based on clinical evaluation by a health care provider. In some embodiments, each of the one or more subsequent treatment cycles is administered ≥ 50 days from the start of the previous treatment cycle. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0319] In some embodiments, treatment according to any of the dosing regimens describedherein is followed by a period wherein the subject does not receive any further FcRn antagonist. Subjects receiving an FcRn antagonist according to any of the dosing regimens described herein may achieve clinical response such that treatment can be withdrawn. In some embodiments, clinical response is defined as MG-ADL response, QMG response, or both MG-ADL response and QMG response. The subject may remain untreated during a period wherein clinical response has been achieved, optionally with a period of further treatment if clinical deterioration occurs. In some embodiments, clinical deterioration refers to new or worsening respiratory / bulbar symptoms or at least a 2-point increase of individual non-ocular MG-ADL items. If, further to treatment according to any of the dosing regimens described herein, clinical response is not achieved or relapse occurs, the subject may undergo a further period of treatment with the FcRn antagonist in accordance with any of the dosing regimens described herein. In some embodiments, a subsequent treatment cycle is 66 BUSINESS.32923153.1administered when the subject exhibits one or more of the following: a total MG-ADL score of ≥ 5; a total MG-ADL score of ≥ 5 with more than 50% of the score due to non-ocular symptoms; a loss of MG-ADL response; and a reduction of total MG-ADL score of < 2 points compared to the score at the previous treatment cycle baseline. In some embodiments, loss of MG-ADL response is defined as no longer showing a decrease of ≥ 2 points on the total MG-ADL score compared to the corresponding treatment cycle baseline. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof. Hypersensitivity and Infusion / Injection-Related Reactions

[0320] Efgartigimod, an FcRn antagonist according to the instant disclosure, was approvedby the FDA in 2021 for the treatment of gMG in adult patients who are anti-AChR antibody positive. VYVGART HYTRULO was approved by the FDA in 2023 for the treatment of gMG in adult patients who are anti-AChR antibody positive. Approval was based upon data establishing the efficacy of efgartigimod in adult patients with gMG who are anti-AChR antibody positive in clinical trial NCT03669588. A total of 167 patients were enrolled in NCT03669588 and were randomized to receive either VYVGART (efgartigimod alfa-fcab) 10mg / kg (1200 mg for those weighing 120 kg or more) (n=84) or placebo (n=83). Baseline characteristics were similar between treatment groups. Patients had a median age of 46 years at screening (range: 19 to 81 years) and a median time since diagnosis of 9 years. Seventy-one percent were female, and 84% were White. Median MG-ADL total score was 9, and median Quantitative Myasthenia Gravis (QMG) total score was 16. The majority of patients (n=65 for VYVGART; n=64 for placebo) were positive for AChR antibodies.

[0321] At baseline, over 80% of patients in each group received AChE inhibitors, over 70%in each treatment group received steroids, and approximately 60% in each treatment group received NSISTs, at stable doses.

[0322] Patients were treated with VYVGART at the recommended dosage regimen describedabove.

[0323] The efficacy of VYVGART was measured using the Myasthenia Gravis-SpecificActivities of Daily Living scale (MG-ADL) which assesses the impact of gMG on daily functions of 8 signs or symptoms that are typically affected in gMG. Each item is assessed on a 4-point scale where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function. A total score ranges from 0 to 24, with the higher scores indicating more impairment. In this study, an MG-ADL responder was defined as a patient with a 2-point or greater reduction in 67 BUSINESS.32923153.1the total MG-ADL score compared to the treatment cycle baseline for at least 4 consecutive weeks, with the first reduction occurring no later than 1 week after the last injection of the cycle.

[0324] The primary efficacy endpoint was the comparison of the percentage of MG-ADLresponders during the first treatment cycle between treatment groups in the AChR-Ab positive population. A statistically significant difference favoring VYVGART was observed in the MG-ADL responder rate during the first treatment cycle [67.7% in the VYVGART-treated group vs 29.7% in the placebo-treated group (p <0.0001)].

[0325] The efficacy of VYVGART was also measured using the Quantitative MyastheniaGravis (QMG) total score which is a 13-item categorical grading system that assesses muscle weakness. Each item is assessed on a 4-point scale where a score of 0 represents no weakness and a score of 3 represents severe weakness. A total possible score ranges from 0 to 39, where higher scores indicate more severe impairment. In this study, a QMG responder was defined as a patient who had a 3-point or greater reduction in the total QMG score compared to the treatment cycle baseline for at least 4 consecutive weeks, with the first reduction occurring no later than 1 week after last injection of the cycle.

[0326] The secondary endpoint was the comparison of the percentage of QMG respondersduring the first treatment cycle between both treatment groups in the AChR-Ab positive patients. A statistically significant difference favoring VYVGART was observed in the QMG responder rate during the first treatment cycle [63.1% in the VYVGART-treated group vs 14.1% in the placebo- treated group (p <0.0001)].

[0327] VYVGART HYTRULO was initially approved with no contraindications.Hypersensitivity reactions, including rash, angioedema, and dyspnea, were observed in the clinical trials. Urticaria was also observed in patients treated with VYVGART HYTRULO. These hypersensitivity reactions were mild-to-moderate, occurred within 1 hour to 3 weeks of administration, and did not lead to treatment discontinuation. No injection-related reactions were reported.

[0328] Since approval of VYVGART HYTRULO in 2023, the following unexpected newadverse reactions have been studied in patients receiving intravenous efgartigimod alfa-fcab: hypersensitivity reactions including anaphylaxis and hypotension, and administration-related reactions. Unexpectedly, anaphylaxis and hypotension leading to syncope occurred during or within an hour of administration and led to administration discontinuation and in some cases to permanent discontinuation. 68 BUSINESS.32923153.1

[0329] Thus, in some embodiments, subjects treated in accordance with the methodsdescribed herein are monitored for a hypersensitivity reaction selected from the group consisting of anaphylaxis and hypotension leading to syncope, and appropriate measures are instituted if needed. In some embodiments, the subjects are monitored for at least 30 minutes after administration of the FcRn antagonist. In some embodiments, the FcRn antagonist is administered to the subject via subcutaneous administration over at least 20-30 seconds. In some embodiments, the appropriate measure to be initiated following detection of anaphylaxis and / or hypotension leading to syncope is discontinuation of the subcutaneous administration. In some embodiments, the appropriate measure to be initiated following detection of anaphylaxis and / or hypotension leading to syncope is permanent discontinuation of treatments with the FcRn antagonist. In some embodiments, the subject is informed of the signs and symptoms of a hypersensitivity reaction, such as anaphylaxis and / or hypotension leading to syncope, and is advised to contact a healthcare provider immediately should they occur. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0330] Administration-related reactions reported with intravenous efgartigimod alfa-fcabfollowing initial approval (i.e., postmarketing) include hypertension, chills, shivering, thoracic pain, abdominal pain, and back pain. Administration-related reactions occurred during or within an hour of administration and led to administration discontinuation.

[0331] Thus, in some embodiments, subjects treated in accordance with the methodsdescribed herein are monitored for an injection-related reaction, and the injection is discontinued if an injection-related reaction is detected. In some embodiments, the subjects are monitored during administration of the FcRn antagonist and for 1 hour after administration. In some embodiments, the subject is rechallenged with the FcRn antagonist when the injection-related reaction is mild-to- moderate as determined by a health care provider. In some embodiments, rechallenging comprises one or more of close clinical observation, slower injection rate, and pre-medication. In some embodiments, rechallenging comprises close clinical observation, slower administration rate, and pre- medication. In some embodiments, the injection is discontinued when the injection-related reaction is severe and appropriate therapy is initiated. In some embodiments, the FcRn antagonist is readministered following a severe injection-related reaction if the benefit is determined to justify the potential risk. In some embodiments, a determination of a mild-to-moderate injection-related reaction or a severe injection-related reaction is made by a health care provider based upon guidance in the Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0, published November 27, 2017 (evs.nci.nih.gov / ftp1 / CTCAE / CTCAE_5.0 / ). In some embodiments, the injection-related 69 BUSINESS.32923153.1reaction comprises one or more of the following: hypertension, chills, shivering, thoracic pain, abdominal pain, and back pain. In some embodiments, the subject is advised of the potential risk of an injection-related reaction. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof.

[0332] In any of the above methods, the FcRn antagonist may be comprised in apharmaceutical composition as described herein. In some embodiments, the pharmaceutical composition comprises 200 mg / mL of an FcRn antagonist, 2000 U / mL rHuPH20, 20 mM L- histidine / L-histidine hydrochloride, 70 mM sodium chloride, 50 mM L-arginine hydrochloride, 60 mM sucrose, 10 mM L-methionine, and 0.04% (w / ) polysorbate 80, at a pH of 6.0. In some embodiments, the FcRn antagonist is efgartigimod, or a biosimilar version thereof. Approved Products

[0333] The present disclosure also provides approved products containing efgartigimod forthe treatment of gMG. Methods of treating gMG comprising administering an approved product containing efgartigimod are also provided. Use of an approved product containing efgartigimod for the treatment of gMG is also provided.

[0334] In some embodiments, the approved product is for subcutaneous administration. Insome embodiments, the approved product is a pre-filled syringe containing efgartigimod.

[0335] In some embodiments, the approved product is provided in a pre-filled syringecontaining 200 mg / mL efgartigimod, 2000 U / mL rHuPH20, 10.5 mg / mL L-arginine hydrochloride, 1.4 mg / mL L-histidine, 2.2 mg / mL L-histidine hydrochloride monohydrate, 1.5 mg / mL L- methionine, 0.4 mg / mL polysorbate 80, 4.1 mg / mL sodium chloride, 20.5 mg sucrose, and water for injection, USP, at a pH of 6.0.

[0336] In some embodiments, the product is approved for treatment of gMG in adult patientswho are anti-AChR antibody positive. In some embodiments, the product is approved for treatment of gMG in adult patients who do not have sufficient response to steroids or non-steroidal immunosuppressive therapies.

[0337] In some embodiments, the approved product is a reference product.

[0338] In some embodiments, the label for the approved product includes a contraindicationin patients with serious hypersensitivity to efgartigimod alfa products, to hyaluronidase, or to any excipients in formulations thereof. In some embodiments, the label for the approved product includes a warning for hypersensitivity reactions selected from anaphylaxis and hypotension leading to 70 BUSINESS.32923153.1syncope. In some embodiments, the label for the approved product includes a warning for infusion- related reactions selected from hypertension, chills, shivering, thoracic pain, abdominal pain, and back pain. In some embodiments, the label for the approved product states to initiate appropriate therapy when a severe infusion-related reaction occurs. In some embodiments, the label of the approved product states that patients may be rechallenged with close clinical observation, slower infusion rates, and pre-medications when a mild-to-moderate infusion-related reaction occurs. In some embodiments, the label of the approved product includes data demonstrating an MG-ADL response rate of 67.7% and a QMG response rate of 63.1% in a population of patients who received 10 mg / kg efgartigimod, compared to a MG-ADL response rate of 29.7% and a QMG response rate of 14.1% in a population of patients who received placebo. In some embodiments, the label of the approved product includes a combination of any of the features described above or elsewhere herein.

[0339] Biosimilars and bioequivalents of the approved product described herein are alsoencompassed by the instant disclosure.

[0340] Methods of treating gMG comprising administering an approved product containingefgartigimod, a biosimilar of an approved product containing efgartigimod, or a bioequivalent of an approved product containing efgartigimod to a subject are also provided. Use of an approved product containing efgartigimod, a biosimilar of an approved product containing efgartigimod, or a bioequivalent of an approved product containing efgartigimod for the treatment of gMG in a subject is also provided.

[0341] In some embodiments, the approved product, biosimilar, or bioequivalent isadministered to the subject once weekly. In some embodiments, the approved product, biosimilar, or bioequivalent is administered to the subject once weekly for 4 weeks.

[0342] In some embodiments, the approved product, biosimilar, or bioequivalent isadministered to the subject using a phased dosing schedule comprising a first treatment cycle and one or more subsequent treatment cycles, wherein the first treatment cycle and the one or more subsequent treatment cycles each independently comprise administration of 1-5 doses of the approved product, biosimilar, or bioequivalent within 1 month. In some embodiments, the first treatment cycle comprises weekly administration of the approved product, biosimilar, or bioequivalent for 4 weeks. In some embodiments, the one or more subsequent treatment cycles each comprise weekly administration of the approved product, biosimilar, or bioequivalent for 4 weeks. In some embodiments, each of the one or more subsequent treatment cycles is administered to the subject 71 BUSINESS.32923153.1based on clinical evaluation. In some embodiments, each of the one or more subsequent treatment cycles is administered to the subject ≥ 50 days from the start of the previous treatment cycle.

[0343] In some embodiments, treatment according to any of the dosing regimens describedherein is followed by a period wherein the subject does not receive any further treatment with the approved product, biosimilar, or bioequivalent. Subjects receiving an approved product, biosimilar, or bioequivalent according to any of the dosing regimens described herein may achieve clinical response such that treatment can be withdrawn. In some embodiments, clinical response is defined as MG-ADL response, QMG response, or both MG-ADL response and QMG response. The subject may remain untreated during a period wherein clinical response has been achieved, optionally with a period of further treatment if clinical deterioration occurs. In some embodiments, clinical deterioration refers to new or worsening respiratory / bulbar symptoms or at least a 2-point increase of individual non-ocular MG-ADL items. If, further to treatment according to any of the dosing regimens described herein, clinical response is not achieved or relapse occurs, the subject may undergo a further period of treatment with the approved product, biosimilar, or bioequivalent in accordance with any of the dosing regimens described herein. In some embodiments, a subsequent treatment cycle is administered when the subject exhibits one or more of the following: a total MG-ADL score of ≥ 5; a total MG-ADL score of ≥ 5 with more than 50% of the score due to non-ocular symptoms; a loss of MG-ADL response; and a reduction of total MG-ADL score of < 2 points compared to the score at the previous treatment cycle baseline. In some embodiments, loss of MG-ADL response is defined as no longer showing a decrease of ≥ 2 points on the total MG-ADL score compared to the corresponding treatment cycle baseline.

[0344] In some embodiments, the subject is anti-AChR antibody positive. In someembodiments, the subject does not have sufficient response to steroids or non-steroidal immunosuppressive therapies.

[0345] In some embodiments, the methods or uses described herein further comprisemonitoring the subject for a hypersensitivity reaction selected from the group consisting of anaphylaxis and hypotension leading to syncope; and initiating an appropriate measure to mitigate the hypersensitivity reaction when detected.

[0346] In some embodiments, the methods or uses described herein further comprisemonitoring the subject for an infusion-related reaction; and discontinuing the infusion when an infusion-related reaction is detected. In some embodiments, the infusion-related reaction comprises 72 BUSINESS.32923153.1one or more of the following: hypertension, chills, shivering, thoracic pain, abdominal pain, and back pain.

[0347] In some embodiments, the methods and uses described herein further compriseadministering to the subject a vaccine as needed at any time during treatment with the approved product, biosimilar, or biological product, wherein the vaccine is not a live-attenuated or live vaccine.

[0348] In some embodiments, the subject is a human, such as, for example, an adult human.EXAMPLES

[0349] The invention will be further understood with reference to the following non-limitingexamples. Example 1: Label with Prescribing Information

[0350] The text below is derived from the most current label with the prescribing information forVYVGART® HYTRULO (efgartigimod alfa and hyaluronidase-qvfc) injection, for subcutaneous use, as approved by Food and Drug Administration (Initial U.S. Approval: 2023, revised Apr 2025). HIGHLIGHTS OF PRESCRIBING INFORMATION

[0351] These highlights do not include all the information needed to use VYVGART HYTRULOsafely and effectively. See full prescribing information for VYVGART HYTRULO. VYVGART HYTRULO® (efgartigimod alfa and hyaluronidase-qvfc) injection, for subcutaneous use Initial U.S. Approval: 2023 RECENT MAJOR CHANGES

[0352] Indications and Usage (1) 6 / 2024

[0353] Dosage and Administration (2.1) 8 / 2024

[0354] Dosage and Administration (2.2, 2.3, 2.4, 2.5) 4 / 2025

[0355] Warnings and Precautions (5.1) 8 / 2024INDICATIONS AND USAGE

[0356] VYVGART HYTRULO is a combination of efgartigimod alfa, a neonatal Fc receptorblocker, and hyaluronidase, an endoglycosidase, indicated for the treatment of adult patients with: generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. (1) 73 BUSINESS.32923153.1DOSAGE AND ADMINISTRATION

[0357] See Full Prescribing Information for instructions on dosage, preparation, andadministration. (2.1, 2.2, 2.3, 2.4, 2.5)

[0358] Evaluate the need to administer age-appropriate vaccines according to immunizationguidelines before initiation of a new treatment cycle with VYVGART HYTRULO. (2.1)

[0359] Important Administration Information^ VYVGART HYTRULO is for subcutaneous use only. (2.2)^ Prefilled syringe can be administered by patients and / or caregivers. (2.2)^ Vial to be administered with a winged infusion set by a healthcare professional only. (2.2)

[0360] gMG: recommended dose and dose schedule^ Administer in cycles of once weekly injections for 4 weeks. (2.3)^ Prefilled syringe: 1,000 mg efgartigimod alfa and 10,000 units hyaluronidase administeredover 20 to 30 seconds. (2.3) ^Vial: 1,008 mg efgartigimod alfa and 11,200 units hyaluronidase over 30 to 90 seconds. (2.3)^ Administer subsequent treatment cycles based on clinical evaluation; safety of initiatingsubsequent cycles sooner than 50 days from the start of the previous treatment cycle has not been established. (2.3) DOSAGE FORMS AND STRENGTHS

[0361] Injection: 1,000 mg efgartigimod alfa and 10,000 units hyaluronidase per 5 mL (200mg / 2,000 units per mL) in a single-dose prefilled syringe. (3)

[0362] Injection: 1,008 mg efgartigimod alfa and 11,200 units hyaluronidase per 5.6 mL (180mg / 2,000 units per mL) in a single-dose vial. (3) CONTRAINDICATIONS

[0363] VYVGART HYTRULO is contraindicated in patients with serious hypersensitivity toefgartigimod alfa products, to hyaluronidase, or to any of the excipients of VYVGART HYTRULO. (4) WARNINGS AND PRECAUTIONS 74 BUSINESS.32923153.1

[0364] Infections: Delay administration of VYVGART HYTRULO to patients with an activeinfection. Monitor for signs and symptoms of infection in patients treated with VYVGART HYTRULO. If serious infection occurs, administer appropriate treatment and consider withholding VYVGART HYTRULO until the infection has resolved. (5.1)

[0365] Hypersensitivity Reactions: Anaphylaxis, hypotension leading to syncope, angioedema,dyspnea, rash, and urticaria have occurred in patients treated with VYVGART HYTRULO or intravenous efgartigimod alfa-fcab product. If a hypersensitivity reaction occurs, the healthcare professional should institute appropriate measures if needed or the patient should seek medical attention. (4, 5.2)

[0366] Infusion / injection-Related Reactions: If a severe infusion / injection-related reactionoccurs, initiate appropriate therapy; consider the risks and benefits of readministering. If a mild to moderate infusion / injection-related reaction occurs, may rechallenge with close clinical observation, slower infusion / injection rates, and pre-medications. (5.3) ADVERSE REACTIONS

[0367] The most common adverse reactions (≥ 10%) in patients with gMG treated withefgartigimod alfa-fcab were respiratory tract infections, headache, and urinary tract infection.

[0368] Injection site reactions were common (≥ 15%) in patients with gMG who were treatedwith VYVGART HYTRULO (6.1)

[0369] To report SUSPECTED ADVERSE REACTIONS, contact argenx at 1-833-argx411 orFDA at 1-800-FDA-1088 or fda.gov / medwatch. DRUG INTERACTIONS

[0370] Closely monitor for reduced effectiveness of medications that bind to the human neonatalFc receptor. When concomitant long-term use of such medications is essential for patient care, consider discontinuing VYVGART HYTRULO and using alternative therapies. (7)

[0371] See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patientlabeling. FULL PRESCRIBING INFORMATION: CONTENTS*

[0372] 1 INDICATIONS AND USAGE

[0373] 2 DOSAGE AND ADMINISTRATION75 BUSINESS.32923153.1

[0374] 2.1 Recommended Vaccination

[0375] 2.2 Important Dosage and Administration Instructions

[0376] 2.3 Recommended Dosage for gMG

[0377] 2.5 Preparation and Administration Instructions

[0378] 3 DOSAGE FORMS AND STRENGTHS

[0379] 4 CONTRAINDICATIONS

[0380] 5 WARNINGS AND PRECAUTIONS

[0381] 5.1 Infections

[0382] 5.2 Hypersensitivity Reactions

[0383] 5.3 Infusion / Injection-Related Reactions

[0384] 6 ADVERSE REACTIONS

[0385] 6.1 Clinical Trials Experience

[0386] 6.2 Postmarketing Experience

[0387] 7 DRUG INTERACTIONS

[0388] 7.1 Effect of VYVGART HYTRULO on Other Drugs

[0389] 8 USE IN SPECIFIC POPULATIONS

[0390] 8.1 Pregnancy

[0391] 8.2 Lactation

[0392] 8.4 Pediatric Use

[0393] 8.5 Geriatric Use

[0394] 8.6 Renal Impairment

[0395] 11 DESCRIPTION

[0396] 12 CLINICAL PHARMACOLOGY

[0397] 12.1 Mechanism of Action

[0398] 12.2 Pharmacodynamics

[0399] 12.3 Pharmacokinetics

[0400] 12.6 Immunogenicity

[0401] 13 NONCLINICAL TOXICOLOGY

[0402] 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

[0403] 14 CLINICAL STUDIES

[0404] 14.1 Generalized Myasthenia Gravis

[0405] 16 HOW SUPPLIED / STORAGE AND HANDLING76 BUSINESS.32923153.1

[0406] 17 PATIENT COUNSELING INFORMATION

[0407] *Sections or subsections omitted from the full prescribing information are not listed1 INDICATIONS AND USAGE

[0408] VYVGART HYTRULO is indicated for the treatment of adult patients with:^ generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibodypositive 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Vaccination

[0409] Evaluate the need to administer age-appropriate vaccines according to immunizationguidelines before initiation of a new treatment cycle with VYVGART HYTRULO. Because VYVGART HYTRULO causes transient reduction in IgG levels, vaccination with live vaccines is not recommended during treatment with VYVGART HYTRULO. [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)]. 2.2 Important Dosage and Administration Instructions

[0410] VYVGART HYTRULO is for subcutaneous use only. Do not administer intravenously.Do not dilute VYVGART HYTRULO.

[0411] Single-Dose Prefilled Syringe

[0412] VYVGART HYTRULO prefilled syringe may be administered by patients and / orcaregivers after proper instruction in subcutaneous injection technique [see Instructions for Use].

[0413] Single-Dose Vial

[0414] VYVGART HYTRULO vial is to be administered with a winged infusion set by ahealthcare professional only [see Dosage and Administration (2.4)]. 2.3 Recommended Dosage for gMG Single-Dose Prefilled Syringe

[0415] The recommended dosage of VYVGART HYTRULO prefilled syringe is 1,000 mg / 10,000 units (1,000 mg efgartigimod alfa and 10,000 units hyaluronidase) administered subcutaneously over approximately 20 to 30 seconds in cycles of once weekly injections for 4 weeks. Single-Dose Vial 77 BUSINESS.32923153.1

[0416] The recommended dosage of VYVGART HYTRULO vial is 1,008 mg / 11,200 units(1,008 mg efgartigimod alfa and 11,200 units hyaluronidase) administered subcutaneously over approximately 30 to 90 seconds in cycles of once weekly injections for 4 weeks. General Dosage Considerations

[0417] Administer subsequent treatment cycles according to clinical evaluation. The safety ofinitiating subsequent cycles sooner than 50 days from the start of the previous treatment cycle has not been established.

[0418] If a scheduled dose is missed, VYVGART HYTRULO may be administered up to 3 daysafter the scheduled time point. Thereafter, resume the original dosing schedule until the treatment cycle is completed. 2.5 Preparation and Administration Instructions

[0419] Single-Dose Prefilled Syringe^ Take the VYVGART HYTRULO prefilled syringe out of the refrigerator at least 30 minutesbefore injecting to allow it to reach room temperature [see How Supplied / Storage and Handling (16)]. Do not use external heat sources to bring the syringe to room temperature. ^Parenteral drug products should be inspected visually for particulate matter and discolorationprior to administration, whenever solution and container permit. Visually inspect that the prefilled syringe solution is yellowish, clear to opalescent and devoid of particulate matter. Do not use if visible particles are present. ^Each prefilled syringe is for one-time use only.^ To administer VYVGART HYTRULO prefilled syringe, use a safety needle that is 25G, 5 / 8inches in length, and thin wall type. The safety needle is not included in the carton. ^Choose an injection site on the abdomen (at least 2 inches away from the navel).o Do not inject on areas where the skin is irritated, red, bruised, infected, tender, hard,or into areas where there are moles or scars. oRotate injection sites for subsequent administrations.^ Inject VYVGART HYTRULO prefilled syringe subcutaneously into a pinched skin area at anangle of 45 to 90 degrees for approximately 20 to 30 seconds. ^Discard any unused portions of medicine remaining in the syringe.78 BUSINESS.32923153.1^ Localized injection site reactions may occur after VYVGART HYTRULO is administered[see Adverse Reactions (6.1)]. ^Monitor for clinical signs and symptoms of hypersensitivity reactions for at least 30 minutesafter administration. If a hypersensitivity reaction occurs, the patient should seek medical attention and the healthcare professional should institute appropriate measures, if needed [see Warnings and Precautions (5.2)].

[0420] For detailed instructions on the preparation and administration of VYVGART HYTRULOprefilled syringe see INSTRUCTIONS FOR USE.

[0421] Single-Dose Vial

[0422] Use aseptic technique when preparing and administering VYVGART HYTRULO vial. Donot shake the vial. Each vial is for one time use only. Avoid exposure to direct sunlight.

[0423] Preparation• Take the VYVGART HYTRULO vial out of the refrigerator at least 15 minutes beforeinjecting to allow it to reach room temperature [see How Supplied / Storage and Handling (16)]. Do not use external heat sources. •Check that the VYVGART HYTRULO solution is yellowish, clear to opalescent.• Parenteral medicine products should be inspected visually for particulate matter prior toadministration, whenever solution and container permit. Do not use if opaque particles or other foreign particles are present. •Withdraw the entire content of VYVGART HYTRULO from the vial using apolypropylene syringe and an 18G stainless steel transfer needle. •Remove large air bubbles, if present.• Each vial contains overfill to compensate for liquid loss during preparation and tocompensate for the priming volume of the winged infusion set. •VYVGART HYTRULO vial does not contain preservatives. Administer immediately afterpreparation.

[0424] Administration• To administer VYVGART HYTRULO vial, use a winged infusion set made of polyvinylchloride (PVC), 25G, 12 inches tubing, maximum priming volume of 0.4 mL. •Remove the transfer needle from the syringe and connect the syringe to the wingedinfusion set. 79 BUSINESS.32923153.1• Prior to administration, fill the tubing of the winged infusion set by gently pressing thesyringe plunger until the plunger is at 5.6 mL. There should be solution at the end of the winged infusion set needle. •Choose an injection site on the abdomen (at least 2 to 3 inches away from the navel).o Do not inject on areas where the skin is red, bruised, tender, hard, or into areaswhere there are moles or scars. oRotate injection sites for subsequent administrations.• Inject VYVGART HYTRULO vial subcutaneously into a pinched skin area at an angle ofabout 45 degrees over 30 to 90 seconds. •Localized injection site reactions may occur after VYVGART HYTRULO isadministered. [see Adverse Reactions (6.1)]. •Discard any unused portions of medicine remaining in the vial, the syringe and the wingedinfusion set. •Healthcare professionals should monitor for clinical signs and symptoms ofhypersensitivity reactions for at least 30 minutes after administration. If a hypersensitivity reaction occurs, the healthcare professional should institute appropriate measures if needed or the patient should seek medical attention [see Warnings and Precautions (5.2)]. 3 DOSAGE FORMS AND STRENGTHS

[0425] Injection: 1,000 mg efgartigimod alfa and 10,000 units hyaluronidase per 5 mL (200mg / 2,000 units per mL) as yellowish, clear to opalescent solution, in a single-dose prefilled syringe.

[0426] Injection: 1,008 mg efgartigimod alfa and 11,200 units hyaluronidase per 5.6 mL (180mg / 2,000 units per mL) as yellowish, clear to opalescent solution, in a single-dose vial.

[0427] 4 CONTRAINDICATIONS

[0428] VYVGART HYTRULO is contraindicated in patients with serious hypersensitivity toefgartigimod alfa products, to hyaluronidase, or to any of the excipients of VYVGART HYTRULO. Reactions have included anaphylaxis and hypotension leading to syncope [see Warnings and Precautions (5.2)]. 5 WARNINGS AND PRECAUTIONS 80 BUSINESS.32923153.15.1 Infections

[0429] VYVGART HYTRULO may increase the risk of infection. The most common infectionsobserved in Study 1 were urinary tract infection (10% of efgartigimod alfa-fcab-treated patients compared to 5% of placebo-treated patients) and respiratory tract infections (33% of efgartigimod alfa-fcab-treated patients compared to 29% of placebo-treated patients) [see Adverse Reactions (6.1) and Clinical Studies (14)]. A higher frequency of patients who received efgartigimod alfa-fcab compared to placebo were observed to have below normal levels for white blood cell counts (12% versus 5%, respectively), lymphocyte counts (28% versus 19%, respectively), and neutrophil counts (13% versus 6%, respectively). The majority of infections and hematologic abnormalities were mild to moderate in severity. Delay VYVGART HYTRULO administration in patients with an active infection until the infection is resolved. During treatment with VYVGART HYTRULO, monitor for clinical signs and symptoms of infections. If serious infection occurs, administer appropriate treatment and consider withholding VYVGART HYTRULO until the infection has resolved. Immunization

[0430] Evaluate the need to administer age-appropriate vaccines according to immunizationguidelines before initiation of a new treatment cycle with VYVGART HYTRULO. The safety of immunization with live vaccines and the immune response to vaccination during treatment with VYVGART HYTRULO are unknown. Because VYVGART HYTRULO causes a reduction in IgG levels, vaccination with live vaccines is not recommended during treatment with VYVGART HYTRULO. 5.2 Hypersensitivity Reactions

[0431] In clinical trials, hypersensitivity reactions, including rash, angioedema, and dyspnea wereobserved in patients treated with VYVGART HYTRULO or intravenous efgartigimod alfa-fcab. Urticaria was also observed in patients treated with VYVGART HYTRULO. Hypersensitivity reactions were mild or moderate, occurred within one hour to three weeks of administration.

[0432] Anaphylaxis and hypotension leading to syncope have been reported in postmarketingexperience with intravenous efgartigimod alfa-fcab. Anaphylaxis and hypotension occurred during or within an hour of administration and led to infusion discontinuation and in some cases to permanent treatment discontinuation. 81 BUSINESS.32923153.1

[0433] Monitor for clinical signs and symptoms of hypersensitivity reactions for at least 30minutes after administration [see Dosage and Administration (2.4)]. If a hypersensitivity reaction occurs, the healthcare professional should institute appropriate measures if needed or the patient should seek medical attention. VYVGART HYTRULO is contraindicated in patients with a history of serious hypersensitivity to efgartigimod alfa products, to hyaluronidase, or to any of the excipients of VYVGART HYTRULO [see Contraindications (4)]. 5.3 Infusion / Injection-Related Reactions

[0434] Infusion-related reactions have been reported with intravenous efgartigimod alfa-fcab inpostmarketing experience. The most frequent symptoms and signs were hypertension, chills, shivering, and thoracic, abdominal, and back pain. Infusion-related reactions occurred during or within an hour of administration and led to infusion discontinuation. If a severe infusion / injection- related reaction occurs, initiate appropriate therapy. Consider the risks and benefits of readministering VYVGART HYTRULO following a severe infusion / injection-related reaction. If a mild to moderate infusion / injection-related reaction occurs, patients may be rechallenged with close clinical observation, slower infusion / injection rates, and pre-medications. 6 ADVERSE REACTIONS

[0435] The following clinically significant adverse reactions are described elsewhere in thelabeling: ^Infections [see Warnings and Precautions (5.1)]^ Hypersensitivity Reactions [see Warnings and Precautions (5.2)]^ Infusion / Injection-Related Reactions [see Warnings and Precautions (5.3)]6.1 Clinical Trials Experience

[0436] Because clinical trials are conducted under widely varying conditions, adverse reactionrates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Experience in Patients with gMG

[0437] The safety of efgartigimod alfa in patients with gMG was established in a double blindedplacebo- controlled study with efgartigimod alfa-fcab administered intravenously (Study 1) and its 82 BUSINESS.32923153.1open-label extension, and in an active-controlled study of VYVGART HYTRULO administered subcutaneously (Study 2) and its open-label extension [see Clinical Studies (14.1)]. Adverse Reactions with Efgartigimod Alfa-fcab Intravenous in Patients with gMG

[0438] In clinical studies, the safety of efgartigimod alfa-fcab administered intravenously hasbeen evaluated in 246 patients with gMG who received at least one dose of efgartigimod alfa-fcab, including 57 patients exposed to at least 7 treatment cycles and 8 patients exposed to at least 10 treatment cycles.

[0439] In a placebo-controlled study (Study 1) in patients with gMG, 84 patients receivedefgartigimod alfa-fcab 10 mg / kg [see Clinical Studies (14)]. Of these 84 patients, approximately 75% were female, 82% were White, 11% were Asian, and 8% were of Hispanic or Latino ethnicity. The mean age at study entry was 46 years (range 19 to 78).

[0440] The minimum time to initiate a subsequent cycle, specified by study protocol, was 50 daysfrom the start of the previous treatment cycle. On average, efgartigimod alfa-fcab-treated patients received 2 cycles in Study 1. The mean and median times to the second treatment cycle were 94 days and 72 days from the initial infusion of the first treatment cycle, respectively, for efgartigimod alfa- fcab-treated patients.

[0441] Adverse reactions reported in at least 5% of patients treated with efgartigimod alfa-fcaband more frequently than placebo are summarized in Table 4. The most common adverse reactions (reported in at least 10% of efgartigimod alfa-fcab-treated patients) were respiratory tract infection, headache, and urinary tract infection. Table 4: Adverse Reactions in at least 5% of Patients with gMG Treated with Efgartigimod Alfa-fcab Intravenously (EFG IV) and More Frequently than in Placebo-Treated Patients in Study 1 (Safety Population) Adverse reaction EFG IV PlaceboBUSINESS.32923153.1Adverse Reactions with VYVGART HYTRULO in Patients with gMG

[0442] In an active-controlled study in patients with gMG (Study 2), 110 patients wererandomized and received one cycle of once weekly administrations for 4 weeks (4 administrations total), of either VYVGART HYTRULO subcutaneously (n=55) or efgartigimod alfa-fcab intravenously (n=55) at recommended doses [see Dosage and Administration (2.2)]. The open-label extension of Study 2 included some patients who switched from efgartigimod alfa-fcab IV to VYVGART HYTRULO.

[0443] The most common adverse reactions (reported in at least 10% of VYVGART HYTRULO-treated patients) were injection site reactions and headache.

[0444] In Study 2, injection site reactions occurred in 38% of patients receiving VYVGARTHYTRULO. These were injection site rash, erythema, pruritus, bruising, pain, and urticaria.

[0445] In Study 2 and its open-label extension (n = 168), all injection site reactions were mild tomoderate in severity and did not lead to treatment discontinuation. The majority occurred within 24 hours after administration and resolved spontaneously. Most injection site reactions occurred during the first treatment cycle, and the incidence decreased with each subsequent cycle. 6.2 Postmarketing Experience

[0446] The following adverse reactions have been identified during postapproval use ofefgartigimod alfa products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

[0447] Immune System Disorders: Hypersensitivity reactions including anaphylaxis andhypotension, and infusion / injection-related reactions [see Warnings and Precautions (5.2, 5.3)]. 7 DRUG INTERACTIONS7.1 Effect of VYVGART HYTRULO on Other Drugs

[0448] Concomitant use of VYVGART HYTRULO with medications that bind to the humanneonatal Fc receptor (FcRn) (e.g., immunoglobulin products, monoclonal antibodies, or antibody derivates containing the human Fc domain of the IgG subclass) may lower systemic exposures and reduce effectiveness of such medications. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. When concomitant long-term use of such medications is 84 BUSINESS.32923153.1essential for patient care, consider discontinuing VYVGART HYTRULO and using alternative therapies. 8 USE IN SPECIFIC POPULATIONS 8.1 PregnancyPregnancy Exposure Registry

[0449] There is a pregnancy exposure registry that monitors pregnancy outcomes in womenexposed to VYVGART HYTRULO during pregnancy. Healthcare providers and patients may call 1- 855-272-6524 or go to Vyvgartpregnancy.com to enroll in or to obtain information about the registry. Risk Summary

[0450] There are no available data on the use of VYVGART HYTRULO or efgartigimod alfacontaining products during pregnancy. There was no evidence of adverse developmental outcomes following the intravenous administration of efgartigimod alfa at up to 100 mg / kg / day in rats and rabbits (see Data).

[0451] The background rate of major birth defects and miscarriage in the indicated population isunknown. In the U.S. general population, the estimated background rate of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal / Neonatal Adverse Reactions

[0452] Monoclonal antibodies are increasingly transported across the placenta as pregnancyprogresses, with the largest amount transferred during the third trimester. Therefore, efgartigimod alfa may be transmitted from the mother to the developing fetus.

[0453] As VYVGART HYTRULO is expected to reduce maternal IgG antibody levels, reductionin passive protection to the newborn is anticipated. Risk and benefits should be considered prior to administering live vaccines to infants exposed to VYVGART HYTRULO in utero [see Warnings and Precautions (5.1)]. Data Animal Data 85 BUSINESS.32923153.1

[0454] VYVGART HYTRULO for subcutaneous injection contains efgartigimod alfa andhyaluronidase [see Description (11)].

[0455] Efgartigimod alfa:^ Intravenous administration of efgartigimod alfa (0, 30, or 100 mg / kg / day) to pregnant rats andrabbits throughout organogenesis resulted in no adverse effects on embryofetal development in either species. Maternal efgartigimod alfa exposures at the highest no-effect doses were approximately 8 and 62 times, respectively, that in humans at the recommended human dose (RHD) of 1008 mg. ^Intravenous administration of efgartigimod alfa (0, 30, or 100 mg / kg / day) to rats throughoutgestation and lactation resulted in no adverse effects on pre- or postnatal development. Maternal exposures at the highest no-effect dose were approximately 13 times that in humans at the RHD.

[0456] Hyaluronidase:^ In a study in which hyaluronidase (human recombinant) was administered by subcutaneousinjection to pregnant mice throughout organogenesis, increased embryofetal mortality and decreased fetal body weights were observed at the highest doses tested. The no-effect dose for adverse effects on embryofetal development in the mouse was approximately 1800 times the dose of hyaluronidase at the recommended human dose (RHD) of VYVGART HYTRULO (1,008 mg efgartigimod alfa and 11,200 U hyaluronidase), on a U / kg basis. ^There were no adverse effects on pre- and postnatal development following subcutaneousadministration of hyaluronidase (human recombinant) to mice throughout gestation and lactation at doses up to 5,000 times the dose of hyaluronidase at the RHD of VYVGART HYTRULO, on a U / kg basis. 8.2 Lactation Risk Summary

[0457] There is no information regarding the presence of efgartigimod alfa or hyaluronidase, fromadministration of VYVGART HYTRULO, in human milk, the effects on the breastfed infant, or the effects on milk production. Maternal IgG is known to be present in human milk. 86 BUSINESS.32923153.1

[0458] The developmental and health benefits of breastfeeding should be considered along withthe mother’s clinical need for VYVGART HYTRULO and any potential adverse effects on the breastfed infant from VYVGART HYTRULO or from the underlying maternal condition. 8.4 Pediatric Use

[0459] Safety and effectiveness in pediatric patients have not been established.8.5 Geriatric Use

[0460] Clinical studies of VYVGART HYTRULO did not include sufficient numbers of patientsaged 65 and older to determine whether they respond differently from younger adult patients. 8.6 Renal Impairment

[0461] No dose adjustment of VYVGART HYTRULO is needed for patients with mild renalimpairment. There are insufficient data to evaluate the impact of moderate renal impairment (eGFR 30-59 mL / min / 1.73 m²) and severe renal impairment (eGFR <30 mL / min / 1.73 m²) on pharmacokinetic parameters of VYVGART HYTRULO [see Clinical Pharmacology (12.3)]. 11 DESCRIPTION

[0462] VYVGART HYTRULO is a fixed-combination drug product containing efgartigimod alfaand hyaluronidase (human recombinant).

[0463] Efgartigimod alfa, a neonatal Fc receptor blocker, is a human immunoglobulin G1 (IgG1)-derived Fc fragment (fragment, crystallized) of the za allotype, produced in Chinese hamster ovary (CHO) cells. The efgartigimod alfa Fc fragment is a homodimer consisting of two identical peptide chains each consisting of 227 amino acids linked together by two interchain disulfide bonds with affinity for FcRn. The molecular weight of efgartigimod alfa is approximately 54 kDa.

[0464] Hyaluronidase (human recombinant) is an endoglycosidase used to increase the dispersionand absorption of co-administered drugs when administered subcutaneously. Hyaluronidase (human recombinant) is a glycosylated single-chain protein produced by Chinese hamster ovary cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20). Hyaluronidase (human recombinant) has a molecular weight of approximately 61 kDa. 87 BUSINESS.32923153.1

[0465] VYVGART HYTRULO (efgartigimod alfa and hyaluronidase-qvfc) injection is a sterile,preservative free, yellowish, clear to opalescent solution supplied in a single-dose prefilled syringe or vial for subcutaneous injection.

[0466] Each 5 mL single-dose prefilled syringe contains 1,000 mg of efgartigimod alfa and10,000 units of hyaluronidase (human recombinant). Each mL contains 200 mg of efgartigimod alfa, 2,000 units of hyaluronidase (human recombinant) and arginine hydrochloride (10.5 mg), histidine (1.4 mg), L-histidine hydrochloride monohydrate (2.2 mg), methionine (1.5 mg), polysorbate 80 (0.4 mg), sodium chloride (4.1 mg), sucrose (20.5 mg), and Water for Injection, USP, at a pH of 6.0.

[0467] Each 5.6 mL single-dose vial contains 1,008 mg of efgartigimod alfa and 11,200 units ofhyaluronidase (human recombinant). Each mL contains 180 mg of efgartigimod alfa, 2,000 units of hyaluronidase (human recombinant) and histidine (1.4 mg), L-histidine hydrochloride monohydrate (2.2 mg), methionine (1.5 mg), polysorbate 20 (0.4 mg), sodium chloride (5.8 mg), sucrose (20.5 mg), and Water for Injection, USP, at a pH of 6.0. 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action

[0468] VYVGART HYTRULO is a coformulation of efgartigimod alfa and hyaluronidase.

[0469] Efgartigimod alfa is a human IgG1 antibody fragment that binds to the neonatal Fcreceptor (FcRn), resulting in the reduction of circulating IgG.

[0470] Hyaluronidase increases permeability of the subcutaneous tissue by depolymerizinghyaluronan. This effect is transient and permeability of the subcutaneous tissue is restored within 24 to 48 hours. 12.2 Pharmacodynamics

[0471] In Study 1 [see Clinical Studies (14)], the pharmacological effect of efgartigimod alfa-fcab was assessed by measuring the decrease in serum IgG levels and AChR autoantibody levels. In patients testing positive for AChR antibodies and who were treated with efgartigimod alfa-fcab intravenous, there was a reduction in total IgG levels relative to baseline. Decrease in AChR autoantibody levels followed a similar pattern. A decrease in AChR-Ab was associated with a clinical response in AChR-Ab positive patients, as measured by the change from baseline in MG-ADL total score. 88 BUSINESS.32923153.1

[0472] In Study 2, the pharmacological effect of VYVGART HYTRULO administeredsubcutaneously (SC) at 1,008 mg / 11,200 Units was compared to efgartigimod alfa-fcab administered intravenously at 10 mg / kg (EFG IV) in gMG patients. The maximum mean reduction in AChR-Ab level was observed at week 4, with a mean reduction of 62.2% and 59.7% in the VYVGART HYTRULO SC and efgartigimod alfa-fcab IV arm, respectively. The decrease in total IgG levels followed a similar pattern. The 90% confidence intervals for the geometric mean ratios of AChR-Ab reduction at day 29 and AUEC0-4w(area under the effect-time curve from time 0 to 4 weeks post dose) were within the range of 80% to 125%, indicating no clinically significant difference between the two formulations. 12.3 Pharmacokinetics

[0473] Efgartigimod alfa exposures were approximately dose-proportional up to the highestsubcutaneously tested dose of VYVGART HYTRULO (1750 mg, 1.75 times the recommended dosage).

[0474] Absorption

[0475] The rate and extent of absorption from a single-dose prefilled syringe and single-dosevial are similar. Distribution

[0476] The volume of distribution is 15 to 20L.Metabolism and Elimination

[0477] Efgartigimod alfa and hyaluronidase are expected to be degraded by proteolytic enzymesinto small peptides and amino acids.

[0478] The terminal half-life is 80 to 120 hours (3 to 5 days).

[0479] After a single intravenous dose of 10 mg / kg efgartigimod alfa-fcab in healthy subjects,less than 0.1% of the administered dose was recovered in urine. Specific Populations Age, Sex and Race 89 BUSINESS.32923153.1

[0480] A population pharmacokinetics analysis assessing the effects of age, body weight, sex,and race did not suggest any clinically significant impact of these covariates on efgartigimod alfa exposures. Body Weight

[0481] A population pharmacokinetics analysis suggests that the influence of body weight onefgartigimod alfa exposure after administration of VYVGART HYTRULO SC 1008 mg was limited and not clinically relevant. Patients with Renal Impairment

[0482] No dedicated pharmacokinetic study has been performed in patients with renalimpairment.

[0483] Population PK analyses of data from the VYVGART HYTRULO clinical studiesindicated that patients with mild renal impairment (eGFR 60-89 mL / min / 1.73 m²) had 11 to 20% increase in exposure relative to the exposure in patients with normal renal function [see Use in Specific Populations (8.6)]. Patients with Hepatic Impairment

[0484] No dedicated pharmacokinetic study has been performed in patients with hepaticimpairment. Hepatic impairment is not expected to affect the pharmacokinetics of efgartigimod alfa. Drug Interaction Studies

[0485] Clinical drug interactions studies have not been performed with efgartigimod alfa.P450 Enzymes

[0486] Efgartigimod alfa is not metabolized by cytochrome P450 enzymes; therefore, interactionswith concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely. Drug Interactions with Other Drugs or Biological Products

[0487] Efgartigimod alfa may decrease concentrations of compounds that bind to the human FcRn[see Drug Interactions (7.1)]. 12.6 Immunogenicity

[0488] The observed incidence of anti-drug antibodies is highly dependent on the sensitivity andspecificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug 90 BUSINESS.32923153.1antibodies in other studies, including those of VYVGART HYTRULO or of other efgartigimod products.

[0489] In Study 2, in up to 10 weeks following the initiation of a treatment period with 4 weeklyadministrations, the incidence of anti-efgartigimod alfa antibodies was 35% (19 / 55) following treatment with VYVGART HYTRULO and 20% (11 / 55) in patients receiving intravenous efgartigimod alfa-fcab. For both IV and SC arms, neutralizing anti-efgartigimod alfa antibodies were detected in 4% (2 / 55) of patients.

[0490] In Study 3, in up to 12 weeks of treatment in stage A and 48 weeks in stage B, the incidenceof anti-efgartigimod alfa antibodies was 6% (20 / 317) in stage A and 2% (2 / 111) in stage B, following treatment with VYVGART HYTRULO. Neutralizing anti-efgartigimod alfa antibodies were detected in 0.3% (1 / 317) of patients in stage A and in no patient in stage B.

[0491] Some neutralizing antibodies may not be detected by the assay. The available data are toolimited to make definitive conclusions regarding immunogenicity and the effect on pharmacokinetics, safety, or efficacy of VYVGART HYTRULO. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

[0492] VYVGART HYTRULO for subcutaneous injection contains efgartigimod alfa andhyaluronidase [see Description (11)]. Carcinogenesis and Mutagenesis

[0493] No studies have been conducted to assess the carcinogenic potential of efgartigimod alfa.

[0494] No studies have been conducted to assess the genotoxic potential of efgartigimod alfa.

[0495] No carcinogenicity or genotoxicity studies were conducted for human recombinanthyaluronidase. Impairment of Fertility

[0496] Intravenous administration of efgartigimod alfa (0, 30, or 100 mg / kg / day) to male andfemale rats prior to and during mating and continuing in females through gestation day 7 resulted in no adverse effects on fertility. Efgartigimod alfa exposures at the highest no-effect dose were approximately 12 times that in humans at the recommended human dose of 1008 mg. 91 BUSINESS.32923153.1

[0497] There were no effects on reproductive tissues in monkeys following subcutaneousadministration of hyaluronidase (human recombinant) doses up to approximately 1,200 times the dose of hyaluronidase at the recommended human dose (RHD) of VYVGART HYTRULO (1,008 mg efgartigimod alfa and 11,200 U hyaluronidase) on a U / kg basis for 39 weeks. No systemic exposure to hyaluronidase was observed at doses up to approximately 120 times the dose of hyaluronidase at the RHD of VYVGART HYTRULO, on a U / kg basis. 14 CLINICAL STUDIES 14.1 Generalized Myasthenia Gravis

[0498] Study 1 (described below) which established the effectiveness of efgartigimod alfa-fcabfor the treatment of generalized myasthenia gravis (gMG) in adults who are AChR antibody positive was conducted with efgartigimod alfa-fcab intravenous formulation. In Study 2, VYVGART HYTRULO demonstrated a comparable pharmacodynamic effect on AChR antibody reduction as compared to the efgartigimod alfa-fcab intravenous formulation, which established the efficacy of VYVGART HYTRULO [see Clinical Pharmacology (12.2)]. Study 1 (Efgartigimod Alfa-fcab Intravenous)

[0499] The efficacy of efgartigimod alfa-fcab intravenous (EFG IV) for the treatment ofgeneralized myasthenia gravis (gMG) in adults who are AChR antibody positive was established in a 26-week, multicenter, randomized, double-blind, placebo-controlled trial (Study 1; NCT03669588).

[0500] Study 1 enrolled patients who met the following criteria at screening:^ Myasthenia Gravis Foundation of America (MGFA) clinical classification class II to IV^ MG-Activities of Daily Living (MG-ADL) total score of ≥ 5^ On stable dose of MG therapy prior to screening, that included acetylcholinesterase (AChE)inhibitors, steroids, or non-steroidal immunosuppressive therapies (NSISTs), either in combination or alone ^IgG levels of at least 6 g / L

[0501] A total of 167 patients were enrolled in Study 1 and were randomized to receive eitherEFG IV 10mg / kg (1200 mg for those weighing 120 kg or more) (n=84) or placebo (n=83). Baseline characteristics were similar between treatment groups. Patients had a median age of 46 years at screening (range: 19 to 81 years) and a median time since diagnosis of 7 years. Seventy-one percent 92 BUSINESS.32923153.1were female, and 84% were White. Median MG-ADL total score was 9, and median Quantitative Myasthenia Gravis (QMG) total score was 16. The majority of patients (n=65 for EFG IV; n=64 for placebo) were positive for AChR antibodies.

[0502] At baseline, over 80% of patients in each group received AChE inhibitors, over 70% ineach treatment group received steroids, and approximately 60% in each treatment group received NSISTs, at stable doses.

[0503] Patients were treated with 10 mg / kg EFG IV administered as an intravenous infusion overone hour once weekly for 4 weeks. In patients weighing 120 kg or more, EFG IV was administered as 1200 mg per infusion. Subsequent treatment cycles were administered based on clinical evaluation, but no sooner than 50 days from the start of the previous treatment cycle.

[0504] The efficacy of EFG IV was measured using the Myasthenia Gravis-Specific Activities ofDaily Living scale (MG-ADL) which assesses the impact of gMG on daily functions of 8 signs or symptoms that are typically affected in gMG. Each item is assessed on a 4-point scale where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function. A total score ranges from 0 to 24, with the higher scores indicating more impairment. In this study, an MG-ADL responder was defined as a patient with a 2-point or greater reduction in the total MG-ADL score compared to the treatment cycle baseline for at least 4 consecutive weeks, with the first reduction occurring no later than 1 week after the last infusion of the cycle.

[0505] The primary efficacy endpoint was the comparison of the percentage of MG-ADLresponders during the first treatment cycle between treatment groups in the AChR-Ab positive population. A statistically significant difference favoring EFG IV was observed in the MG-ADL responder rate during the first treatment cycle [67.7% in the EFG IV-treated group vs 29.7% in the placebo-treated group (p <0.0001)].

[0506] The efficacy of EFG IV was also measured using the Quantitative Myasthenia Gravis(QMG) total score which is a 13-item categorical grading system that assesses muscle weakness. Each item is assessed on a 4-point scale where a score of 0 represents no weakness and a score of 3 represents severe weakness. A total possible score ranges from 0 to 39, where higher scores indicate more severe impairment. In this study, a QMG responder was defined as a patient who had a 3-point or greater reduction in the total QMG score compared to the treatment cycle baseline for at least 4 consecutive weeks, with the first reduction occurring no later than 1 week after last infusion of the cycle. 93 BUSINESS.32923153.1

[0507] The secondary endpoint was the comparison of the percentage of QMG responders duringthe first treatment cycle between both treatment groups in the AChR-Ab positive patients. A statistically significant difference favoring EFG IV was observed in the QMG responder rate during the first treatment cycle [63.1% in the EFG IV-treated group vs 14.1% in the placebo-treated group (p <0.0001)].

[0508] The results are presented in Table 5.Table 5: MG-ADL and QMG Responders During Cycle 1 in AChR-Ab Positive Patients (mITT Analysis Set) EFG IV Placebo P-value Odds Ratio (95% CI) =65 =64 ) ) lyLiving; QMG=Quantitative Myasthenia Gravis; mITT=modified intent-to-treat; n=number of patients for whom the observation was reported; CI = confidence interval. Logistic regression stratified for AChR-Ab status (if applicable), Japanese / Non-Japanese and standard of care, with baseline MG-ADL as covariate / QMG as covariates. Two-sided exact p-value. 16 HOW SUPPLIED / STORAGE AND HANDLING

[0509] VYVGART HYTRULO (efgartigimod alfa and hyaluronidase-qvfc) injection is apreservative free, sterile, yellowish, clear to opalescent solution supplied as a single-dose prefilled syringe or vial. Single-Dose Prefilled Syringe

[0510] Each single-dose prefilled syringe contains 1,000 mg efgartigimod alfa and 10,000 unitshyaluronidase per 5 mL (200 mg / 2,000 units per mL). It is available in cartons of one or four single- dose prefilled syringes (NDC 73475-1221-1 or NDC 73475-1221-4). The safety needle that is 25G, 5 / 8 inches length, and thin wall type is not included in the carton.

[0511] Store VYVGART HYTRULO prefilled syringe refrigerated at 2°C to 8°C (36°F to 46°F)in the original carton to protect from light until time of use. Do not freeze. Do not shake.

[0512] If needed, prefilled syringes may be stored at room temperature at up to 30°C (86°F) inthe original carton for a single period of up to 30 days after removing from refrigerator or until 94 BUSINESS.32923153.1expiration date on the carton, whichever occurs first. Record the date removed from the refrigerator on the carton. Single-Dose Vial

[0513] Each single-dose vial contains 1,008 mg efgartigimod alfa and 11,200 units hyaluronidaseper 5.6 mL (180 mg / 2,000 units per mL). It is available in carton of one single-dose vial (NDC 73475- 3102-3).

[0514] Store VYVGART HYTRULO vials refrigerated at 2°C to 8°C (36°F to 46°F) in theoriginal carton to protect from light until time of use. Do not freeze. Do not shake.

[0515] If needed, unopened vials may be stored in the original carton for up to 3 days at roomtemperature at 20°C to 25°C (68°F to 77°F) for a single period before administration or returned to refrigeration. Do not store the vial at room temperature more than one time. Record the date removed from and the date returned to the refrigerator on the carton.

[0516] 17 PATIENT COUNSELING INFORMATION

[0517] Advise the patient and / or caregiver to read FDA-approved patient labeling (PatientInformation and Instructions for Use). Infections

[0518] Instruct patients to communicate any history of infections to the healthcare provider andto contact their healthcare provider if they develop any symptoms of an infection. Advise patients to complete age-appropriate vaccines according to immunization guidelines prior to initiation of a new treatment cycle with VYVGART HYTRULO. Administration of live vaccines is not recommended during treatment with VYVGART HYTRULO [see Warnings and Precautions (5.1)]. Hypersensitivity Reactions

[0519] Inform patients that hypersensitivity reactions, including angioedema and anaphylaxis,have occurred in patients who were treated with efgartigimod alfa products. Inform patients about the signs and symptoms of these reactions, and advise patients to contact their healthcare provider immediately if these occur [see Warnings and Precautions (5.2)]. 95 BUSINESS.32923153.1Infusion / injection-Related Reactions

[0520] Advise patients of the potential risk of infusion / injection-related reactions, which caninclude hypertension, chills, shivering, and chest, abdominal, and back pain. [see Warnings and Precautions (5.3)]. Instruction on Injection Technique

[0521] If a patient or caregiver is to administer subcutaneous VYVGART HYTRULO prefilledsyringe, instruct them in proper injection technique (e.g., site selection and duration of injection) [see Instructions for Use]. Pregnancy Registry

[0522] There is a pregnancy exposure registry that monitors pregnancy outcomes in womenexposed to VYVGART HYTRULO during pregnancy. Encourage participation and advise patients about how they may enroll in the registry [see Use in Specific Populations (8.1)]. Example 2: Instructions For Use

[0523] VYVGART HYTRULO (efgartigimod alfa and hyaluronidase-qvfc) injection, forsubcutaneous use 1,000 mg and 10,000 units / 5 mL Important information you need to know before injecting VYVGART HYTRULO

[0524] VYVGART HYTRULO is for under the skin (subcutaneous) injection only.

[0525] Be sure to read and understand this Instructions for Use before injecting VYVGARTHYTRULO. Your healthcare provider should show you or your caregiver how to prepare and inject VYVGART HYTRULO the right way before using it for the first time. Ask your healthcare provider if you have any questions.

[0526] The prefilled syringe is for one-time-use only and cannot be reused.

[0527] Do not use VYVGART HYTRULO if it has been at room temperature for longer than 30days.

[0528] Do not use the prefilled syringe if it is expired.

[0529] Do not use the prefilled syringe if it is cracked, broken, or damaged. Return damagedprefilled syringes to the specialty pharmacy. 96 BUSINESS.32923153.1

[0530] Do not use a prefilled syringe if the liquid medicine is discolored or contains particles.The liquid medicine should look clear to yellowish in color. A little cloudiness is normal.

[0531] Do not shake the prefilled syringe.

[0532] You will need supplies that are not provided with VYVGART HYTRULO.Storing VYVGART HYTRULO Prefilled Syringe

[0533] Store VYVGART HYTRULO in the refrigerator between 36°F to 46°F (2°C to 8°C).

[0534] Keep the prefilled syringes in the original carton to protect them from light until ready touse.

[0535] Keep VYVGART HYTRULO and all medicines out of the reach of children.

[0536] Do not freeze the prefilled syringes or store them in direct sunlight.

[0537] Do not use a prefilled syringe that has been frozen or left in direct sunlight.Prefilled Syringe Parts

[0538] FIG. 1 is a schematic of the parts of the prefilled syringe and the safety needle (notprovided with VYVGART HYTRULO prefilled syringe) that is 25G, 5 / 8-inch length, thin wall. Gather and Check the Prefilled Syringe

[0539] 1. Remove the carton from refrigerator

[0540] 1.1. Remove the carton containing the prefilled syringe from the refrigerator.

[0541] 1.2. Remove 1 prefilled syringe from the carton and place any remaining prefilled syringesback into the refrigerator for later use.

[0542] 1.3. Remove the prefilled syringe from the tray.

[0543] 2. Check the prefilled syringe before use

[0544] 2.1. Check the expiration date on the prefilled syringe label. Do not use the prefilledsyringe if the expiration date has passed.

[0545] 2.2. Check the condition of the prefilled syringe and the prefilled syringe cap. Do not usethe prefilled syringe if it is cracked, broken, damaged, or if the prefilled syringe cap is missing.

[0546] 2.3. Check the appearance of the liquid medicine in the prefilled syringe. The liquidmedicine should look clear to yellowish in color. A little cloudiness is normal. Do not use the prefilled syringe if the liquid medicine is discolored or contains particles. 97 BUSINESS.32923153.1Prepare for the Injection

[0547] 3. Allow the prefilled syringe to warm to room temperature

[0548] 3.1. Place the prefilled syringe on a clean flat surface and let it sit for at least 30 minutes,to allow it to warm to room temperature. Do not attempt to warm the prefilled syringe in any other way. Do not use the VYVGART HYTRULO prefilled syringe if it has been at room temperature for longer than 30 days.

[0549] 4. Gather supplies and wash your hands

[0550] 4.1. Gather the following supplies that are not provided with the prefilled syringe: safetyneedle, alcohol swab, sharps disposal container, sterile gauze and / or bandage (as needed).

[0551] 4.2. Wash your hands with soap and water.

[0552] 5. Snap off the prefilled syringe cap and attach the safety needle

[0553] 5.1. Carefully open the safety needle package and remove the needle (see FIG. 2A).Throw away the packaging into household trash.

[0554] 5.2. Bend the prefilled syringe cap to one side to snap it off and remove it from the prefilledsyringe (see FIG. 2B). Throw away the prefilled syringe cap into the household trash. Do not touchthe tip of the prefilled syringe after the prefilled syringe cap has been removed.

[0555] 5.3. Hold the prefilled syringe by the syringe body in one hand, and attach the safety needleto the prefilled syringe by twisting it to the right (clockwise) until you feel resistance (see FIG.2C). The safety needle is now attached to the prefilled syringe (see FIG.2D).

[0556] 6. Choose and clean the injection site on stomach (abdomen)

[0557] 6.1. Choose an injection site on the stomach (abdomen) at least 2 inches away from thebelly button (navel) (see FIG. 3A). Change (rotate) the injection site the next time you inject VYVGART HYTRULO. Do not inject into skin that is irritated, red, bruised, infected, or tender. Do not inject into skin that is hard, scarred, or has moles. Do not inject into a vein. VYVGART HYTRULO is for under the skin (subcutaneous) injection only.

[0558] 6.2. Clean the chosen injection site with an alcohol swab and let it air dry. Do not blow onor touch the injection site after it has been cleaned. Inject VYVGART HYTRULO

[0559] 7. Pull back the needle shield and remove the clear needle cap98 BUSINESS.32923153.1

[0560] 7.1. Pull the needle shield back (see FIG. 3B). Note: The needle shield will be used afterthe injection to cover the needle and protect from needle-stick injuries.

[0561] 7.2. Hold the prefilled syringe body and remove the clear needle cap by pulling it straightoff of the needle (see FIG. 3C). Throw away the clear needle cap into the household trash. Do notrecap the needle.

[0562] 8. Give the injection

[0563] 8.1. Pinch the cleaned injection site. While pinching the skin, insert the needle at a 45 to90 degree angle all the way into the pinched skin (see FIG.4A). Then release the pinched skin. Do not pinch the skin too tightly as this can cause bruising.

[0564] 8.2. Slowly press the thumb pad down all the way until it stops to inject the liquid medicine(see FIG.4B). It will take about 20 to 30 seconds to inject all of the liquid medicine. You will feel resistance as you press down. Inject more slowly in case there is discomfort. It is ok if you need to pause or change your grip during the injection. Do not try to force the thumb pad down quickly as this will make the thumb pad harder to press.

[0565] 8.3. After all the liquid medicine is injected, remove the needle from the skin by pulling itout straight out without changing the angle that it was inserted (see FIG.4C). Throw away (dispose of) the Used Prefilled Syringe

[0566] 9. Cover the needle and throw away the used prefilled syringe

[0567] 9.1. Carefully push the needle shield over the needle until it snaps into place and coversthe needle (see FIG. 5A). This helps to prevent needle-stick injuries. Do not recap the needle usingthe clear needle cap. Only use the needle shield to cover the needle.

[0568] 9.2. Throw away the used prefilled syringe, with the needle still attached, into an FDA-cleared sharps disposal container right away after use (see FIG. 5B). Do not throw away (dispose of)loose needles and syringes in your household trash.

[0569] 10. Treat the injection site

[0570] 10.1. If there is a small amount of blood or liquid at the injection site, press a sterile gauzeover the injection site until the bleeding stops. If needed, you may apply a small adhesive bandage. Additional Disposal Information

[0571] If you do not have an FDA-cleared sharps disposal container, you may use a householdcontainer that is: 99 BUSINESS.32923153.1• made of a heavy-duty plastic, • can be closed with a tight-fitting, puncture-resistant lid without sharps being able to come out, • upright and stable during use, • leak-resistant, and • properly labeled to warn of hazardous waste inside the container.

[0572] When your sharps disposal container is almost full, you will need to follow yourcommunity guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes.

[0573] For more information about safe sharps disposal, and for specific information about sharpsdisposal in the state that you live in, go to the FDA’s website at: fda.gov / safesharpsdisposal. Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container. Always keep the sharps disposal container out of the reach of children. Example 3: Development of Efgartigimod SC Formulation for Prefilled Syringe

[0574] A first-generation formulation of efgartigimod for subcutaneous use (Efgartigimod PH20SC Gen1; VYVGART® HYTRULO) has been approved by the FDA under BLA 761304, for the treatment of gMG in adult patients who are anti-AChR antibody positive.

[0575] In order to provide increased convenience to patients, the PH20 SC Gen1 vial-syringeformulation was adapted for use in a prefilled syringe ready-to-use product. Efgartigimod Concentration

[0576] The vial formulation has an efgartigimod concentration of 180 mg / mL (see Table 6). Eachvial is filled with at least 6 mL of sterile, non-pyrogenic, and preservative-free solution. The volume in the vial is larger than the dose volume to be extracted for administration (approximately 6 mL). The target fill volume is 6.7 mL, including an 8% overfill to allow withdrawal of at least 6.2 mL VYVGART® HYTRULO from the vial. 0.4-0.6 mL is lost in the butterfly tubing used for administration, providing an administered dose of 5.6 mL, or 1008 mg (5.6 mL * 180 mg / mL = 1008 mg). 100 BUSINESS.32923153.1

[0577] The prefilled syringe has a smaller maximum capacity. The target fill volume for theprefilled syringe is 5.181 mL, including a 4% overfill to allow withdrawal of at least 5.0 mL of VYVGART® HYTRULO from the syringe. Therefore, the efgartigimod concentration was increased to 200 mg / mL to give an administered dose of 1000 mg (5 mL * 20 mg / mL = 1000 mg). Table 6. Comparison of Efgartigimod PH20 SC Formulations Formulation / Concentration Component GEN1 SC (Vial) GEN1.1 SC (PFS) GEN2 SC (PFS-2)Polysorbate

[0578] Polysorbates 20 and 80 are used in the formulation of biotherapeutic products both forpreventing surface adsorption and as stabilizers against protein aggregation. The polysorbates are amphipathic, nonionic surfactants composed of fatty acid esters of polyoxyethylene sorbitan, being polyoxyethylene sorbitan monolaurate for polysorbate 20 and polyoxyethylene sorbitan monooleate for polysorbate 80.

[0579] A correlation between PS20 concentration in efgartigimod formulations and onset ofsubvisible particle formulation due to degradation of PS20 in free fatty acids had previously been observed. Therefore, a stability study was conducted using the Efgartigimod 180 mg / mL PH20 SC Gen 1 formulation with varying concentrations of PS20 and PS80.

[0580] Nine formulations differing in type of surfactant (PS20 versus PS80), surfactant grade,surfactant concentrations, and efgartigimod concentration and DS source were stored at +5°C ± 3°C and +25°C ± 2°C for up to 24 months (Table 7). The samples were analyzed for degree of opalescence, 101 BUSINESS.32923153.1pH, protein concentration by OD280, subvisible particles by light obscuration, purity by GP-HPLC, PS concentration by HPLC-FMA and free fatty acid concentration by LC-MS. Table 7: Formulations Evaluated During Surfactant Stability Study Formulation Efgartigimod Conc. PS Purity PS Conc. PS Type ID (mg / mL) Grade (%w / v)or e -con a n ng ormu a ons, resu s emons ra e an mprove s a y profilewith increasing PS20 concentration. Increasing the PS20 concentration delays the onset of subvisible particle formation due to the increased solubility of the generated free fatty acids in the PS20 micelles. All PS20-containing formulations demonstrated a decrease in PS20 content over the course of the study.

[0582] For the PS80-containing formulations, no increase in subvisible particles was observedtogether with a lower increase in % aggregates compared to the PS20-containing formulations. In addition, no decrease in PS80 content was observed over the course of the study. Therefore, PS80 was concluded to be the preferred surfactant to be used in the 200 mg / mL second generation (Gen2) prefilled syringe drug substance formulation.

[0583] Furthermore, the stability study revealed that the stability behavior of the nineformulations was comparable for degree of opalescence, pH, protein concentration and purity. L-arginine 102 BUSINESS.32923153.1

[0584] L-arginine acts as a stabilizer through the slowing down of protein-protein associations,including associations of unfolded proteins (aggregation degradation). Soluble-gel transitions were observed in L-histidine (pH 6.0) formulations containing high concentration (180 mg / mL) efgartigimod upon storage at +5℃ ± 3℃, which were reversible at ambient temperature. However, the soluble-gel transition of a 200 mg / mL efgartigimod formulation was found to effectively be prevented by the addition of L-arginine HCl at a concentration within the range of 20 mM to 200 mM. The addition of L-arginine HCl did not impact the stability behavior of efgartigimod.

[0585] To prevent the soluble-gel transition, decrease viscosity, and limit an increase inosmolality, an L-arginine HCl concentration of 50 mM was selected, resulting in a formulation containing 200 mg / mL efgartigimod, 20 mM L-histidine / L-histidine HCl, 100 mM NaCl, 60 mM sucrose, 0.04% polysorbate 80 and 50 mM L-arginine HCl at pH 6.0. Bioequivalence studies

[0586] A study was conducted to assess pharmacokinetics (PK), pharmacodynamics (PD), andimmunogenicity of the Gen1 SC (Vial) and Gen1.1 SC (PFS) formulations. The study design is shown in FIG.6.

[0587] Subjects received a single dose of efgartigimod PH20 SC 1000 mg in vial + syringe formator prefilled syringe. The evaluation was based on scheduled blood sampling times. Results are shown in FIGs.7A-7C and Tables 8 and 9 below. Bioequivalence criteria were not met due to a higher Cmax leading to an increased efgartigimod bioavailability (AUC). 103 BUSINESS.32923153.1Table 8. Pharmacokinetics of Gen1 SC (Vial) and Gen1.1 SC (PFS) formulations (Geometric Mean). Parameter Vial + Syringe Prefilled Syringe GMR (Reference) (Test) (%) 90% CI (%)Table 9. Pharmacokinetics of Gen1 SC (Vial) and Gen1.1 SC (PFS) formulations (Arithmetic Mean). Parameter (Mean ± SD) Vial + Syringe Prefilled Syringe ]

[0588] The subsequent analysis suggested that the difference in PK was surprisingly driven bythe higher osmolality of the prefilled syringe formulation. A higher osmolality led to faster / higher absorption of efgartigimod, potentially by accelerating lymphatic uptake. If a (highly) hypertonic 104 BUSINESS.32923153.1solution is injected into the subcutaneous space, this is known to create a “shock-effect” on the osmotic balance, to which the lymphatic system responds with a higher drainage of water from the injection spot, carrying any drug product along.

[0589] The increase in osmolality was determined to be partially due to the new formulation andpartially due to a manufacturing artifact. Unexpectedly, residual citrate (40 mM) from the cleaning step had been carried over into the product. The citrate increased osmolality (~Δ120 mOsm / kg), which resulted in higher efgartigimod bioavailability. After the observation, the product was evaluated to be safe for clinical use, and the process was further optimized to avoid carry-over of citrate.

[0590] The 180 mg / mL Efgartigimod SC Gen1 concentrate for solution had an osmolality of 322mOsm / kg H2O, well within the acceptable range for injectable solutions. Several adaptations to the 200 mg / mL Efgartigimod Gen1.1 drug substance formulation were made compared to 180 mg / mL Efgartigimod SC Gen1 drug substance formulation based on the different studies presented above: increasing the protein concentration, changing the surfactant from PS20 to PS80 to improve long- term stability, and adding 50 mM L-arginine HCl to prevent soluble-gel transitions at +5°C ±3°C. These adaptations caused an osmolality increase to 426 mOsm / kg H2O. The residual citrate further increased the osmolality of the Gen1.1 SC (PFS) formulation to 540 mOsm / kg.

[0591] To limit the osmolality increase in the efgartigimod concentrate for solution at 200 mg / mLfollowing the addition of 50 mM L-arginine HCl, it was investigated if the concentration of other excipients could be lowered without impacting product quality attributes.

[0592] Results of the pharmacodynamics studies are shown in Table 10 and FIG. 7D. After asingle injection of Gen1 SC (Vial) and Gen1.1 SC (PFS), the reductions in total IgG over time were similar.Table 10. Pharmacodynamics of Gen1 SC (Vial) and Gen1.1 SC (PFS) formulationsPrefilled syringe Vial + syringe4)BUSINESS.32923153.1iod;ions included in the summary statistics; TEmax=time to reach Emax. Note: TEmax values are presented as median (min, max). Other parameters are presented as arithmetic mean (± SE).

[0593] Results of the immunogenicity study are shown in Table 11. The incidence and prevalenceof ADA against efgartigimod were similar in participants who received efgartigimod PH20 SC via prefilled syringe compared with those who received efgartigimod PH20 SC via vial + syringe. Table 11. Participant Classification, Incidence, and Prevalence of ADA Against Efgartigimod Efgartigimod PH20 SC106 BUSINESS.32923153.1Treatment-induced ADA 24 (40) 27 (45) 51 (43)1 2 2administrationn=number of participants for whom an observation was reported; rHuPH20=recombinant human hyaluronidase PH20; SC=subcutaneous(ly) Notes: ADA incidence was defined as the total number of participants with treatment-boosted or treatment-induced ADA. ADA prevalence was defined as the total number of participants with treatment-unaffected, treatment-boosted, or treatment-induced ADA.aThe denominator for the percentage calculations is the total number of participants per treatment in the safety analysis set.bThe denominator for the percentage calculations is the total number of ADA-evaluable participants in the safety analysis set.

[0594] A two-part study was conducted. In Part A, a formulation robustness study via Design ofExperiments (DOE) was performed on the efgartigimod 180 mg / mL Efgartigimod PH20 SC Gen1 formulation to evaluate the impact of potential variations in the formulation on final drug product quality attributes. Since the concentration of efgartigimod in the Gen1.1 drug substance is set at 200 mg / mL, only excipient variation was examined. Variation in pH was not expected to impact osmolality but pH was added as a parameter to the DOE to investigate the pH limits of the 180 mg / mL Efgartigimod PH20 SC Gen1 formulation. The design consisted of 15 different formulations (Table 12). All formulations were tested at the initial timepoint, after agitation stress, and after long-term storage at +5°C ± 3°C, accelerated temperature conditions at +25°C ± 2°C, and stressed temperature condition at +40°C ± 2°C. The analysis included appearance, pH, protein concentration, subvisible particles, purity by GP-HPLC, icIEF, and CE-SDS (reduced / non-reduced) and PS concentration.

[0595] In Part B, the osmolality of the 180 mg / mL Efgartigimod PH20 SC Gen1 formulation wascompared to the osmolality of the 200 mg / mL efgartigimod formulation, with following adaptations: • Surfactant change from 0.04% PS20 to 0.04% PS80 to improve the stability behavior of the 200 mg / mL efgartigimod formulation; • Addition of L-arginine HCl to prevent soluble-gel transitions; and • Adaptation of NaCl concentration, based on the outcome of part A. 107 BUSINESS.32923153.1

[0596] An overview of the formulations tested in part B is provided in Table 13.Table 12: Formulations Evaluated in the Formulation Robustness Study (Part A) Protein His / His- Formulation Sucrose PS20 L-Met NaCl rHuPH20 Volume pH Conc. HCl )Table 13: Formulations Evaluated in the Osmolality Screening (Part B) Formulation Protein Conc. NaCl L-arginine Surfactant Formulation108 BUSINESS.32923153.1

[0597] From the results of Part A, it could be concluded that decreasing the NaCl concentrationhad no significant impact on the level of subvisible particles, PS20 concentration, % aggregates (GP- HPLC), charged variants (icIEF) and % intact Fc by CE-SDS (non-reduced and reduced). The NaCl concentration showed minor variation in turbidity, with no impact on the product quality. The accelerated temperature condition and shaking stress study indicated no other significant differences (data not shown). In general, the data demonstrated that the NaCl concentration can be lowered without impacting the stability of the efgartigimod 200 mg / mL concentrate for solution.

[0598] The NaCl concentration was then lowered from 100 mM to 70 mM in the newefgartigimod PH20 SC Gen2 formulation, causing the osmolality to decrease to 369 mOsm / kg H2O, close to the osmolality of the 180 mg / mL Efgartigimod SC Gen1 drug substance formulation.

[0599] A study was conducted to assess pharmacokinetics (PK) of the Gen1 SC (Vial) and Gen2SC (PFS) formulations. The study design is shown in FIG. 8. Subjects received a single dose of efgartigimod PH20 SC 1000 mg in vial + syringe format or prefilled syringe. The evaluation was based on scheduled blood sampling times. Results are shown in FIGs.9A-9C and Tables 14 and 15, below. Table 14. Pharmacokinetics of Gen1 SC (Vial) and Gen2 SC (PFS) formulations. (Geometric Mean) Parameter Vial + Syringe Prefilled GMR 9 4 9Table 15. Pharmacokinetics of Gen1 SC (Vial) and Gen2 SC (PFS) formulations. (Arithmetic Mean) Parameter (Mean ± SD) Vial + Syringe Prefilled Syringe109 BUSINESS.32923153.1Cmax, µg / mL 34.5 ± 14.3 37.0 ± 12.7 T h 7199 1200 11928 4800 1200 11925

[0600] This analysis shows that the Gen2 SC (PFS) formulation is bioequivalent to Gen1 SC(Vial). Example 4: Syringe Injection Speed

[0601] The feasibility of different speeds of subcutaneous injections was assessed in a phase 1study with 48 healthy participants. The study design is shown in FIG.10.

[0602] Participants received a single injection of efgartigimod PH20 SC Gen2 (vial + syringe) ata fixed dose of 1000 mg on day 1 and day 8. An assessment of leakage / backflow at the injection site was performed after the injection and was assessed on day 1 and day 8.

[0603] Four different injection speeds were tested: 20, 30, 45 and 60 seconds. The study primaryand secondary endpoints are shown in Table 16 below. Table 16. Study Endpoints Primary Endpoints r eBUSINESS.32923153.1• To determine the feasibility of • Participant injection experience and administering efgartigimod PH20 SC at preference questionnaire, assessed 1 hour y d ,

[0604] Primary endpoint results:• All participants (100%) received at least 90% of the entire injection volume among the 4 injection time groups (injection volume). • There was no meaningful difference in the average volume fluid leakage / backflow at the injection site among the 4 injection time groups and among periods (see FIG.11).

[0605] Secondary endpoint results:• The majority of participants favorably agreed to have the administration again just after the first administration. See Table 17 below. Table 17. Injection experience Timepoint Question Response A: 20B: 30 C: 45 D: 60 Overall ) )111 BUSINESS.32923153.11 Hour I would be willing I strongly11 (91.7) 8 (66.7) 8 (66.7) 9 (75.0) 36 (75.0)after to have the agree ) ) 7)5) 0) ) )5). • Local pain significantly reduced 5 minutes after the injection for all injection speeds (see FIGs.12A-12B). • Efgartigimod PH20 SC administered at different speed groups was well tolerated. Speeds 20 and 60 sec showed tendency for better tolerance (Table 18 and FIGs.13A-13B). • 23% (period 1) and 29% (period 2) of the AEs experienced were ISRs and the majority were erythema and swelling. 112 BUSINESS.32923153.1Table 18. Overview of treatment emergent adverse events (TAEA) A:20 B: 30 C: 45 D: 60 Overall Seconds Seconds Seconds Seconds ) ) ] ) ] ] )113 BUSINESS.32923153.1Total Participants with at5 (41.7) [7] 5 (41.7) [6] 4 (33.3) [4] 5 (41.7) [7] 19 (39.6)Least One TEAE

[0024] ) ] ) ] )

[0606] Participants who received the 20 second injection had lower incidence of ISRs thanparticipants who received the 30, 45, or 60 second injections. The results support an injection speed of less than 30 seconds. Prefilled syringe

[0607] A further study was conducted for 15 patients with gMG and 15 lay caregivers using theprefilled syringe. All subjects (30 / 30) successfully self-injected, demonstrating the suitability of the prefilled syringe for self-administration. 114 BUSINESS.32923153.1

[0608] Two minor use errors occurred, but were not related to the injection itself, and had noimpact on injection or product quality. All knowledge tasks were answered correctly, supporting suitable instructions for use (IFU) for real-world use. The observed injection times are shown in Table 19. Table 19. Observed injection times for prefilled syringe Injection Time n = 28 / 30 (sec)

[0609] The observed injection times support the IFU of 20-30 seconds.Example 5: Evaluation of the Influence of Prefilled Syringe Equilibration Time at Room Temperature, Needle Type and Extrusion Speed On Break Loose and Gliding Force

[0610] Break loose and gliding force (BLGF) experiments were performed to evaluate theinfluence of syringe equilibration time at room temperature (22.5 ± 3.5 °C) (RT), needle type and extrusion speed. The study described herein includes two sets of experiments. The focus of the first set of experiments was on the influence of equilibration time.15, 30 and 60 minutes were selected as reference equilibration times at RT to perform BLGF tests. The second set of experiments focused on the influence of both needle type and extrusion speed on the BLGF. Five different types of needles were tested, each at three different crosshead speeds. Methods BLGF Testing

[0611] The BLGF experiment was performed with a Texture Analyser (TA.XT plus, StableMicrosystems, UK) installed with the 30 kg load cell. The installed accessories were the Syringe testing rig (A / SAE) and the corresponding plunger support. The syringe was assembled by screwing on the plunger rod and removing the syringe closure. In case of needles without safeguard, the needle 115 BUSINESS.32923153.1was screwed into the luer-lock fitting before placing the syringe in the testing rig. In case of needles with a safeguard, the needle was screwed into the luer-lock fitting after placing the syringe in the testing rig. The syringe was subsequently placed in the syringe testing rig. Data was captured and processed by the Exponent software (version 6,1,27,0). Break loose force, minimum gliding force, maximum gliding force and mean gliding force were determined as shown in FIG.14. Viscosity

[0612] A Brookfield viscometer equipped with the RheocalcT software (Brookfield engineeringlaboratories Inc., model DV2T), verified with a 10 mPa.s viscosity standard, was utilized for the viscosity measurement. Measurements were carried-out by a cone and plate viscometer at different temperatures according to the equilibration time (see Table 20). Table 20. Equilibration times and associated temperatures for viscosity measurements Theoretical Equilibration time at RT Temperature (˚C)

[0613] Solutions were measured at 3 different shear rates which corresponded to torque valuesbetween 10% and 90%. Using a micropipette, 0.5 mL of the sample was carefully pipetted in the center of the sample cup attached to the driving motor (CPA-40Z spindle). The sample was equilibrated for at least 30 seconds at the related temperature before the measurement by means of a circulating water bath (model TC-650, Ametek Brookfield temperature control).

[0614] In order to analyze the flow behavior of samples, a linear regression and power law werefitted through the data of shear stress in function of shear rate.

[0615] In case the R2 of the linear regression was equal to or higher than the R2 of the power lawfit, it was concluded that the data was best fitted by a linear regression. In case the 95% confidence interval of the intercept of the linear regression included the origin, the flow behavior was concluded to be Newtonian, whereby the slope of the linear regression was the viscosity of the Newtonian liquid. In case the 95% confidence interval of the intercept of the linear regression did not include the origin, 116 BUSINESS.32923153.1the flow behavior was concluded to correspond to a Bingham plastic, whereby the slope of the linear regression was the plastic viscosity of the Bingham plastic.

[0616] In case the R2 of the power law fit was higher than the R2 of the linear regression throughthe data of shear stress in function of shear rate, the flow behavior could be pseudoplastic or dilatant. If the value of the parameter n in the equation of the power law (equation 1) was smaller than 1, the sample was concluded to be pseudoplastic. If the value of the parameter n was higher than 1, the sample was concluded to be dilatant.

[0617] ^^h^^^^^^ ^^^^^^^^^^^^ = ^^ * (^^h^^^^^^ ^^^^^^^^)^^

[0618] Viscosity measurements were performed on 3 syringes at each equilibration time.Results Equilibration time experiments Temperature determination

[0619] Prefilled syringes (PFS) with 200 mg / mL efgartigimod were provided. PFS were stored at2-8°C and BLGF tests were performed after a target equilibration time (ET) of 12 to 15, 27 to 30 or 57 to 60 minutes at room temperature. Before each BLGF measurement, the temperature of the PFS was measured via an infrared gun measuring over the complete length of the syringe. The temperature of a PFS was also monitored at different time points over the course of 60 minutes in order to evaluate how the temperature evolved. A visualization of the change in temperature over time is given in FIG. 15. The temperature of the lab in which the tests were performed varied between 21.0°C and 22.5°C.

[0620] After pulling the PFS from the fridge, a substantial temperature increase was noticed upuntil 15 minutes. From 15 minutes onward, the temperature increase was observed to be slower until the same temperature as the room was reached at 60 minutes. BLGF in function of equilibration time of PFS at RT

[0621] BLGF were measured to assess extrudability of PFS in relation with ET. Each syringe wasindividually pulled from the fridge and equilibrated for 12 to 15, 27 to 30 or 57 to 60 minutes at RT. The temperature of each syringe was measured as described above. Syringes were assembled with a BD 25G thin wall needle (reference needle) and measured with a crosshead speed of 100 mm / min with the Texture Analyzer TA.Xtplus described above. 117 BUSINESS.32923153.1

[0622] 10 syringes were measured after an ET between 12 and 15 minutes, 27 and 30 minutesand 57 and 60 minutes at RT. Analysis was performed. Overlays of average BLGF curves of PFS with a BD 25G thin wall needle at an extrusion speed of 100 mm / min are given in FIG.16A.

[0623] For the break loose force (BLF), no visual difference was observed between syringeswhich were equilibrated for a different time at RT. For mean gliding force (MGF), however, a clear visual difference was observed. To confirm these findings, statistical analysis to compare means of data sets was performed via a T-test or a Wilcoxon signed-rank test. A visual representation of the evolution of the BLF and MGF in function of ET is given in FIG.16B and FIG.16C, respectively. Conclusions of the statistical testing are found in Table 21 (BLF) and Table 22 (MGF). Table 21. Comparison of data sets of BLF of PFS with a BD 25G thin wall needle at an extrusion speed of 100 mm / min and after 15, 30 or 60 min equilibration at RT Comparison Performed test p-value(1) ConclusionData set 1 Data set 2 15 min ET 30 min ET Wilcoxon Signed-rank test 0.68 No significant difference in BLF30 min ET 60 min ET Wilcoxon Signed-rank test 0.14 No significant difference in BLF15 min ET 60 min ET T-test 0.15 No significant difference in BLF (1) p<0.05: significant difference

[0624] No significant difference in BLF was found between the evaluated ET. This confirms thevisual data. Table 22. Comparison of data sets of MGF of PFS with a BD 25G thin wall needle at an extrusion speed of 100 mm / min and after 15, 30 or 60 min equilibration at RT Comparison Performed test p-value(1) ConclusionData set 1 Data set 2 15 min ET 30 min ET Wilcoxon Signed-rank test 1.50E-3 Significant difference in MGF30 min ET 60 min ET T-test 4.63E-2 Significant difference in MGF15 min ET 60 min ET Wilcoxon Signed-rank test 7.58E-5 Significant difference in MGF(1) p<0.05: significant difference

[0625] Average BLGF profiles are supported by the statistical analysis which shows a significantdifference in MGF between all ET. 118 BUSINESS.32923153.1Viscosity measurements

[0626] Viscosity of 200 mg / mL efgartigimod was measured to assess the influence of ET. To thisend, viscosity measurements were performed at the temperature of PFS right before measurement. 18.5 °C, 20.0 °C and 22.0 °C were selected as temperature setting during viscosity measurements for a target ET of 15, 30 or 60 minutes, respectively. These temperatures were chosen based on the measured temperatures of PFS at different ET. The results of the viscosity measurements are given in Table 23. Table 23. Viscosity of a 200 mg / mL ARGX-113 solution after different ET ET Temperature setting Mean viscosity Std dev. (h:min) (°C) (mPa.s) (mPa.s) 0:12 18.5 12.420.090:30 20.0 11.25 0.07 1:00 22.0 9.98 0.00

[0627] At each ET, the solution had a Newtonian flow behavior. A reduction in viscosity wasobserved at longer ET (see FIG.17A) and thus increased temperature (see FIG.17B).

[0628] A clear trend was observed for temperature and viscosity in function of ET of PFS at RT.A longer equilibration time led to increasing temperature and decreasing viscosity. These factors did not influence the BLF as no significant difference could be found between 15 minutes ET, 30 minutes and 60 minutes ET. However, the factors did influence the MGF. The MGF at 60 minutes ET was significantly lower than the MGF at 30 minutes ET which was again significantly lower than the MGF at 15 minutes ET. Based on this conclusion, 30 minutes was selected as ET for the evaluation of different needle types and extrusion speeds. Evaluation needles and extrusion speed

[0629] In the second set of experiments, PFS were used to examine BLGF with different needletypes and extrusion speeds.50, 100 and 150 mm / min were tested as extrusion speed for each needle type after 30 to 35 minutes of equilibration of the PFS at RT. The different needle types are specified in Table 24. 119 BUSINESS.32923153.1Table 24. Evaluated needle types and references Needle Type Reference Manufacturer 24G regular wall 304100 BDF isgiven in Table 25. Table 25. Overview of averages of BLF Average of BLF (N) Needle type 50 mm / min 100 mm / min 150 mm / min 24G regular wall 6.0109 7.8784 8.5896 25G thin wall (BD) 6.0690 8.1297 9.3140 25G thin wall (McKesson) 6.2370 7.5207 8.5894 25G extra thin wall 6.4376 8.4865 9.1055 25G ultra thin wall 6.0523 7.5627 9.0112

[0631] A general overview of averages of the MGF is given in Table 26.Table 26. Overview of averages of MGF Average of MGF (N) Needle Type 50 mm / min 100 mm / min 150 mm / min 24G regular wall 13.865 25.482 37.725 25G thin wall (BD) 10.261 20.305 30.251 25G thin wall (McKesson) 11.619 20.651 30.080 25G extra thin wall 11.361 23.466 32.713 25G ultra thin wall 10.460 18.924 28.518

[0632] A comparison in BLF and MGF at 50, 100 and 150 mm / min extrusion speed wasperformed for all needle types. A visual comparison of the BLF is given in FIG.18A. The BLF was 120 BUSINESS.32923153.1observed to increase with increasing extrusion speed. A visual comparison of the MGF is given in FIG.18B. The MGF was observed to increase with increasing extrusion speed.

[0633] Statistical tests were performed for each needle to evaluate whether the observed trendsin BLF and MGF in function of extrusion speed were significant or not on a 5% significance level.

[0634] The performed statistical tests indicated for all needle types that there was a significantdifference in BLF and MGF between syringes extruded at 50, 100 and 150 mm / min on a 5% significance level, i.e., BLF and MGF increased at higher extrusion speeds. A comparison in BLF and MGF of different needle types was performed at 50, 100 and 150 mm / min extrusion speed. A comparison of the average BLGF profiles is represented in FIG.19A (150 mm / min), FIG.19B (100 mm / min) and FIG.19C (50 mm / min).

[0635] Statistical analysis on the BLF and MGF of the different needle types measured at 50mm / min, 100 mm / min and 150 mm / min speed was performed. At all evaluated extrusion speeds, no clear trend could be observed in BLF between PFS with the different needle types.

[0636] At an extrusion speed of 150 mm / min, a clear trend in MGF was observed by which aranking could be defined. The ranking is given below.

[0637] 25^^ ^^^^^^< 25 ^^ ^^^^− ^^^^= 25^^ ^^^^− ^^^^< 25^^ ^^^^^^< 24^^ ^^^^

[0638] At an extrusion speed of 100 mm / min, a clear trend in MGF, identical to the trend at 150mm / min, was observed by which a ranking could be defined. At an extrusion speed of 50 mm / min, a trend in MGF, similar to the trends at 100 and 150 mm / min, was observed by which a ranking could be defined. The ranking is given below.

[0639] 25^^ ^^^^^^= 25^^ ^^^^− ^^^^ < 25^^ ^^^^− ^^^^= 25^^ ^^^^^^< 24^^ ^^^^

[0640] The first set of experiments focused on the influence of ET at RT on BLGF of PFS (whichwere stored at 2-8 °C) with a BD 25G thin wall needle as reference at a 100 mm / min extrusion speed. By comparing temperature and viscosity at the defined ET of 15, 30, or 60 minutes, it could be observed that viscosity decreased due to increase of temperature with a longer ET. A significant difference on a 5% significance level was found between 15, 30, and 60 minutes for MGF of which 60 minutes of ET resulted in the lowest MGF and 15 minutes ET resulted in the highest MGF. Based on these data, it was decided to proceed with an ET of 30 minutes for the second set of experiments.

[0641] The second set of experiments focused on the influence of extrusion speed and needle typeon BLGF.50, 100 and 150 mm / min were evaluated as extrusion speeds.24G regular wall, BD 25G thin wall, McKesson 25G thin wall, 25G extra thin wall and 25G ultra thin wall needles were compared. Regarding extrusion speed, a significant difference was observed in BLF and MGF 121 BUSINESS.32923153.1between tests performed at 50, 100 or 150 mm / min, independent of the used needle type, on a 5% significant level. The general trend was that both BLF and MGF were lowest for the 50 mm / min extrusion speed and highest for the 150 mm / min extrusion speed.

[0642] When comparing the different needle types at the same extrusion speed, no clear trendswere observed for the BLF. For the MGF a clear influence of needle type was found for all applied extrusion speeds. The 25G ultra thin wall showed the lowest MGF at all evaluated extrusion speeds. The highest MGF, was found for the 24G regular wall needle at all evaluated extrusion speeds.

[0643] All publications, patents, and patent applications mentioned in this specification areherein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. 122 BUSINESS.32923153.1

Claims

CLAIMS1. A pre-filled syringe containing a liquid pharmaceutical formulation comprising a humanneonatal Fc receptor (FcRn) antagonist and a hyaluronidase, wherein the FcRn antagonist comprises or consists of a variant IgG Fc region, or FcRn-binding fragment thereof, wherein the variant IgG Fc region, or FcRn-binding fragment thereof, comprises or consists of a first Fc domain and a second Fc domain which form a homodimer or a heterodimer, and wherein the first Fc domain and the second Fc domain each comprise amino acids Y, T, E, K, F, and Y at EU positions 252, 254, 256, 433, 434, and 436.

2. The pre-filled syringe of claim 1, wherein the first Fc domain and / or the second Fc domaincomprise an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4.

3. The pre-filled syringe of claim 1 or 2, wherein the first Fc domain and the second Fc domaincomprise an amino acid sequence independently selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4.

4. The pre-filled syringe of any one of claims 1-3, wherein the first Fc domain and the secondFc domain comprise or consist of the amino acid sequence set forth in SEQ ID NO: 1.

5. The pre-filled syringe of any one of claims 1-3, wherein the first Fc domain and the secondFc domain comprise or consist of the amino acid sequence set forth in SEQ ID NO: 2.

6. The pre-filled syringe of any one of claims 1-3, wherein the first Fc domain and the secondFc domain comprise or consist of the amino acid sequence set forth in SEQ ID NO: 3.

7. The pre-filled syringe of any one of claims 1-3, wherein the first Fc domain and the secondFc domain comprise or consist of the amino acid sequence set forth in SEQ ID NO:

4. 123 BUSINESS.32923153.

18. The pre-filled syringe of claim 1, wherein the FcRn antagonist is a population of FcRnantagonist molecules, wherein each FcRn antagonist molecule in the population consists of a dimer of a first Fc domain and a second Fc domain, and wherein the population comprises: (a) a first subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of both the first and the second Fc domains of the FcRn antagonist molecules in the first subpopulation consist of the amino acid sequence set forth in SEQ ID NO: 3; and (b) at least one of: (i) a second subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and the second Fc domains of the FcRn antagonist molecules in the second subpopulation consist of the amino acid sequences set forth in SEQ ID NO: 3 and SEQ ID NO: 13, respectively; (ii) a third subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and the second Fc domains of the FcRn antagonist molecules in the third subpopulation consist of the amino acid sequences set forth in SEQ ID NO: 3 and SEQ ID NO: 10, respectively; (iii) a fourth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of both the first and the second Fc domains of the FcRn antagonist molecules in the fourth subpopulation consist of the amino acid sequence set forth in SEQ ID NO: 3, and wherein two asparagine residues in each FcRn antagonist molecule in the fourth subpopulation are deaminated; (iv) a fifth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and the second Fc domains of the FcRn antagonist molecules in the fifth subpopulation consist of the amino acid sequence set forth in SEQ ID NO: 3, and wherein one asparagine residue in each FcRn antagonist molecule in the fifth subpopulation is deaminated; (v) a sixth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and the second Fc domains of the FcRn antagonist molecules in the sixth subpopulation consist of the amino acid sequences set forth in SEQ ID NO: 2 and SEQ ID NO: 3, respectively; (vi) a seventh subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and the second Fc domains of the FcRn antagonist molecules in the seventh subpopulation consist of the amino acid sequence set forth in SEQ ID NO: 3, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the seventh subpopulation is oxidized; 124 BUSINESS.32923153.1(vii) an eighth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of both the first and the second Fc domains of the FcRn antagonist molecules in the eighth subpopulation consist of the amino acid sequence set forth in SEQ ID NO: 2; (viii) a ninth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and the second Fc domains of the FcRn antagonist molecules in the ninth subpopulation consist of the amino acid sequences set forth in SEQ ID NO: 3 and SEQ ID NO: 7, respectively; (ix) a tenth subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of the first and the second Fc domains of the FcRn antagonist molecules in the tenth subpopulation consist of the amino acid sequences set forth in SEQ ID NO: 2 and SEQ ID NO: 3, respectively, and wherein one methionine residue or one tryptophan residue in each FcRn antagonist molecule in the tenth subpopulation is oxidized; and (x) an eleventh subpopulation of FcRn antagonist molecules, wherein the amino acid sequences of both the first and the second Fc domains of the FcRn antagonist molecules in the eleventh subpopulation consist of the amino acid sequence set forth in SEQ ID NO: 3, and wherein two amino acid residues, independently selected from a methionine residue and a tryptophan residue, in each FcRn antagonist molecule in the eleventh subpopulation is oxidized.

9. The pre-filled syringe of any one of claims 1-8, wherein the FcRn antagonist isefgartigimod, or a biosimilar version thereof.

10. The pre-filled syringe of any one of claims 1-9, wherein the hyaluronidase comprisesrecombinant human PH20 (rHuPH20).

11. The pre-filled syringe of any one of claims 1-10, wherein the liquid pharmaceuticalformulation comprises 160-240 mg / mL, optionally 180-220 mg / mL, optionally 190-210 mg / mL of efgartigimod, or optionally about 200 mg / mL of efgartigimod.

12. The pre-filled syringe of claim 11, wherein the liquid pharmaceutical formulation comprises200 mg / mL of efgartigimod. 125 BUSINESS.32923153.

113. The pre-filled syringe of any one of claims 1-12, wherein the liquid pharmaceuticalformulation comprises 1,400-2,800, optionally 1,600-2,600, optionally 1,800-2,400 Units / mL of the hyaluronidase, or optionally about 2,000 Units / mL of the hyaluronidase.

14. The pre-filled syringe of claim 13, wherein the liquid pharmaceutical formulation comprises2,000 Units / mL of the hyaluronidase.

15. The pre-filled syringe of any one of claims 1, or 10-14, wherein the liquid pharmaceuticalformulation comprises about 2,000 Units / mL of rHuPH20.

16. The pre-filled syringe of claim 15, wherein the liquid pharmaceutical formulation comprises2,000 Units / mL of rHuPH20.

17. The pre-filled syringe of any one of claims 1-16, wherein the liquid pharmaceuticalformulation comprises 4.2-6.2 mL, optionally 4.5-6.9 mL, optionally 4.7-6.2 mL, or optionally about 5.2 mL of liquid.

18. The pre-filled syringe of claim 17, wherein the liquid pharmaceutical formulation has avolume of 5.2 mL of liquid.

19. The pre-filled syringe of claim 17 or 18, wherein the pre-filled syringe comprises anextractable volume of the liquid pharmaceutical formulation of 4-6 mL, optionally 4.3-6.7 mL, optionally 4.5-6.0 mL, or optionally about 5.0 mL of liquid.

20. The pre-filled syringe of claim 17, wherein the extractable volume of the liquidpharmaceutical formulation is 5.0 mL of liquid.

21. The pre-filled syringe of any one of claims 1-20, wherein the liquid pharmaceuticalformulation has an osmolality of 350-380 mOsm / kg H2O.

22. The pre-filled syringe of any one of claims 1-21, wherein the liquid pharmaceuticalformulation has a viscosity of between 8 and 14 mPa s at room temperature. 126 BUSINESS.32923153.

123. The pre-filled syringe of any one of claims 1-22, wherein the liquid pharmaceuticalformulation comprises about 10.5 mg / mL L-arginine hydrochloride, about 1.4 mg / mL L-histidine, about 2.2 mg / mL L-histidine hydrochloride monohydrate, about 1.5 mg / mL L-methionine, about 0.4 mg / mL polysorbate 80, about 4.1 mg / mL sodium chloride, and about 20.5 mg / mL sucrose, at about pH 6.0.

24. The pre-filled syringe of any one of claims 1-22, wherein the liquid pharmaceuticalformulation comprises about 50 mM L-arginine, about 20 mM L-histidine, about 10 mM L- methionine, about 0.04% polysorbate 80, about 70 mM sodium chloride, and about 60 mM sucrose.

25. The pre-filled syringe of any one of claims 1-22, wherein the liquid pharmaceuticalformulation comprises about 50 mM L-arginine hydrochloride, about 20 mM L-histidine and L- histidine hydrochloride monohydrate, about 10 mM L-methionine, about 0.04% polysorbate 80, about 70 mM sodium chloride, and about 60 mM sucrose.

26. The pre-filled syringe of claim 23, wherein the liquid pharmaceutical formulation comprises10.5 mg / mL L-arginine hydrochloride, 1.4 mg / mL L-histidine, 2.2 mg / mL L-histidine hydrochloride monohydrate, 1.5 mg / mL L-methionine, 0.4 mg / mL polysorbate 80, 4.1 mg / mL sodium chloride, and 20.5 mg / mL sucrose, at pH 6.0.

27. The pre-filled syringe of claim 24, wherein the liquid pharmaceutical formulation comprises50 mM L-arginine, 20 mM L-histidine, 10 mM L-methionine, 0.04% polysorbate 80, 70 mM sodium chloride, and 60 mM sucrose.

28. The pre-filled syringe of claim 25, wherein the liquid pharmaceutical formulation comprises50 mM L-arginine hydrochloride, 20 mM L-histidine and L-histidine hydrochloride monohydrate, 10 mM L-methionine, 0.04% polysorbate 80, 70 mM sodium chloride, and 60 mM sucrose.

29. The pre-filled syringe of any one of claims 1-22, wherein the liquid pharmaceuticalformulation comprises about 200 mg / mL efgartigimod, about 2,000 U / mL rHuPH20, about 10.5 mg / mL L-arginine hydrochloride, about 1.4 mg / mL L-histidine, about 2.2 mg / mL L-histidine 127 BUSINESS.32923153.1hydrochloride monohydrate, about 1.5 mg / mL L-methionine, about 0.4 mg / mL polysorbate 80, about 4.1 mg / mL sodium chloride, and about 20.5 mg / mL sucrose, at about pH 6.0.

30. The pre-filled syringe of any one of claims 1-22, wherein the liquid pharmaceuticalformulation comprises about 200 mg / mL efgartigimod, about 2,000 U / mL rHuPH20, about 50 mM L-arginine, about 20 mM L-histidine, about 10 mM L-methionine, about 0.04% polysorbate 80, about 70 mM sodium chloride, and about 60 mM sucrose.

31. The pre-filled syringe of any one of claims 1-22, wherein the liquid pharmaceuticalformulation comprises about 200 mg / mL efgartigimod, about 2,000 U / mL rHuPH20, about 50 mM L-arginine hydrochloride, about 20 mM L-histidine and L-histidine hydrochloride monohydrate, about 10 mM L-methionine, about 0.04% polysorbate 80, about 70 mM sodium chloride, and about 60 mM sucrose.

32. The pre-filled syringe of claim 29, wherein the liquid pharmaceutical formulation comprises200 mg / mL efgartigimod, 2,000 U / mL rHuPH20, 10.5 mg / mL L-arginine hydrochloride, 1.4 mg / mL L-histidine, 2.2 mg / mL L-histidine hydrochloride monohydrate, 1.5 mg / mL L-L- methionine, 0.4 mg / mL polysorbate 80, 4.1 mg / mL sodium chloride, and 20.5 mg / mL sucrose, at pH 6.0.

33. The pre-filled syringe of claim 30, wherein the liquid pharmaceutical formulation comprises200 mg / mL efgartigimod, 2,000 U / mL rHuPH20, 50 mM L-arginine, 20 mM L-histidine, 10 mM L- methionine, 0.04% polysorbate 80, 70 mM sodium chloride, and 60 mM sucrose.

34. The pre-filled syringe of claim 31, wherein the liquid pharmaceutical formulation comprises200 mg / mL efgartigimod, 2,000 U / mL rHuPH20, 50 mM L-arginine hydrochloride, 20 mM L- histidine and L-histidine hydrochloride monohydrate, 10 mM L-methionine, 0.04% polysorbate 80, 70 mM sodium chloride, and 60 mM sucrose.

35. The pre-filled syringe of any one of claims 1-34, comprising:a) a syringe body having a barrel with an interior volume, a distal end, and a proximal end; 128 BUSINESS.32923153.1b) a plunger disposed within the interior volume of the barrel; and c) a nozzle at the distal end of the syringe body, wherein the FcRn antagonist and the hyaluronidase are disposed within the interior volume of the barrel between the plunger and the nozzle.

36. The pre-filled syringe of claim 35, comprising an extractable volume defined as a portion ofthe interior volume between the plunger and the nozzle, the extractable volume being 4.0-6.0 mL, optionally 4.3-5.7 mL, optionally 4.5-5.5 mL, or optionally about 5.0 mL.

37. The pre-filled syringe of claim 36, wherein the extractable volume is 5.0 mL.

38. The pre-filled syringe of any one of claims 35-37, wherein the nozzle has an interior volumeof 0.1 to 0.3 mL.

39. The pre-filled syringe of claim 38, wherein the nozzle has an interior volume of about 0.2mL.

40. The pre-filled syringe of any one of claims 35-39, wherein the plunger comprises a stopperand a thumb pad.

41. The pre-filled syringe of any one of claims 35-40, wherein the syringe body comprises afinger flange at its proximal end.

42. The pre-filled syringe of any one of claims 35-41, further comprising a collar positionedaround the nozzle and a syringe cap removably attached to the distal end of the collar.

43. The pre-filled syringe of claim 42, wherein the syringe cap is attached to the distal end ofthe collar via a frangible connection.

44. The pre-filled syringe of any one of claims 35-43, wherein the syringe body is made of atransparent or translucent material. 129 BUSINESS.32923153.

145. The pre-filled syringe of any one of claims 35-44, wherein the liquid pharmaceuticalformulation is stored in a sterile condition within the syringe body.

46. The pre-filled syringe of any one of claims 35-45, further comprising a needle attached atthe collar.

47. The pre-filled syringe of any one of claims 35-46, wherein the barrel interior volume andplunger are configured to expel 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 liquid pharmaceutical formulation in the barrel in no more than 30 seconds, optionally no more than 28 seconds, optionally no more than 25 seconds, optionally no more than 20 seconds, optionally no more than 15 seconds, or optionally no more than 10 seconds, at room temperature.

48. The pre-filled syringe of any one of claims 35-47, wherein the barrel interior volume andplunger are configured to expel 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 liquid pharmaceutical formulation in the barrel in 10 seconds or greater, optionally in 15 seconds or greater, optionally 18seconds or greater, or optionally 20 seconds or greater, at room temperature.

49. The pre-filled syringe of any one of claims 35-48, wherein the barrel interior volume andplunger are configured to expel at least 95% of the liquid pharmaceutical formulation in the barrel in between 20 to 30, 20 to 28, or 20-25 seconds, at room temperature.

50. The pre-filled syringe of any one of claims 1-49, wherein the pre-filled syringe is an auto-injector.

51. The pre-filled syringe of claim 50, wherein the auto-injector comprises a luer fit needle.

52. The pre-filled syringe of claim 50 or 51, wherein the auto-injector is button activated.

53. The pre-filled syringe of any one of claims 50-52 wherein the auto-injector comprises post-delivery sharps protection. 130 BUSINESS.32923153.

154. The pre-filled syringe of any one of claims 1-53, wherein administration of the liquidpharmaceutical formulation with the pre-filled syringe is bioequivalent to administration of the liquid pharmaceutical formulation with a syringe filled with the liquid pharmaceutical formulation at the time of injection.

55. A kit comprising one or more of the pre-filled syringes of any one of claims 1-54 in one ormore containers.

56. The kit of claim 55, wherein each pre-filled syringe is in a separate sealed wrapper.

57. The kit of claim 55 or 56, wherein the container comprises 2-10 pre-filled syringes.

58. The kit of any one of claims 55-57 further comprising instructions for use of the one or morepre-filled syringes.

59. The kit of any one of claims 55-58 further comprising a needle attachable to the pre-filledsyringe.

60. The kit of claim 59, wherein the needle is 25G.

61. The kit of claim 59 or 60, wherein the needle is 5 / 8” in length.

62. The kit of any one of claims 59-61, wherein the needle further comprises a needle cap.

63. The kit of claim 62, wherein the needle cap is transparent or translucent.

64. The kit of any one of claims 55-63 further comprising a needle shield.

65. The kit of any one of claims 59-64, wherein the needle is in a needle sealed wrapper, and thepre-filled syringe is in a syringe sealed wrapper. 131 BUSINESS.32923153.

166. A method of administering a liquid pharmaceutical formulation comprising an FcRnantagonist and hyaluronidase to a subject comprising: a) placing the pre-filled syringe of any one of claims 1-34 at room temperature until a viscosity of the liquid pharmaceutical formulation is between 8 and 14 mPa s; b) attaching a needle to the pre-filled syringe; c) pinching a site on the abdomen of the subject; d) inserting the needle into the pinched site; e) injecting the FcRn antagonist and the hyaluronidase into the subject; and f) removing the needle from the pinched site, thereby administering the liquid pharmaceutical formulation comprising the FcRn antagonist and the hyaluronidase to the subject.

67. A method of administering a liquid pharmaceutical formulation comprising an FcRnantagonist and hyaluronidase to a subject comprising: a) placing the pre-filled syringe of any one of claims 1-34 at room temperature for at least 30 minutes; b) attaching a needle to the pre-filled syringe; c) pinching a site on the abdomen of the subject; d) inserting the needle into the pinched site; e) injecting the FcRn antagonist and the hyaluronidase into the subject; and f) removing the needle from the pinched site, thereby administering the liquid pharmaceutical formulation comprising the FcRn antagonist and the hyaluronidase to the subject.

68. A method of administering a liquid pharmaceutical formulation comprising an FcRnantagonist and hyaluronidase to a subject comprising: a) placing the pre-filled syringe of any one of claims 35-54 at room temperature until a viscosity of the liquid pharmaceutical formulation is between 8 and 14 mPa s; b) attaching a needle to the pre-filled syringe; c) pinching a site on the abdomen of the subject; d) inserting the needle into the pinched site; e) pushing the plunger; and 132 BUSINESS.32923153.1f) removing the needle from the pinched site, thereby administering the liquid pharmaceutical formulation comprising the FcRn antagonist and the hyaluronidase to the subject.

69. A method of administering a liquid pharmaceutical formulation comprising an FcRnantagonist and hyaluronidase to a subject comprising: a) placing the pre-filled syringe of any one of claims 35-54 at room temperature for at least 30 minutes; b) attaching a needle to the pre-filled syringe; c) pinching a site on the abdomen of the subject; d) inserting the needle into the pinched site; e) pushing the plunger; and f) removing the needle from the pinched site, thereby administering the liquid pharmaceutical formulation comprising the FcRn antagonist and the hyaluronidase to the subject.

70. A method of administering a liquid pharmaceutical formulation comprising an FcRnantagonist and hyaluronidase to a subject comprising: a) placing one or more of the pre-filled syringes from the kit of any one of claims 55-65 at room temperature until a viscosity of the liquid pharmaceutical formulation is between 8 and 14 mPa s; b) attaching a needle to the pre-filled syringe; c) pinching a site on the abdomen of the subject; d) inserting the needle into the pinched site; e) pushing the plunger; and f) removing the needle from the pinched site, thereby administering the liquid pharmaceutical formulation comprising the FcRn antagonist and the hyaluronidase to the subject.

71. A method of administering a liquid pharmaceutical formulation comprising an FcRnantagonist and hyaluronidase to a subject comprising: 133 BUSINESS.32923153.1a) placing one or more of the pre-filled syringes from the kit of any one of claims 55-65 at room temperature for at least 30 minutes; b) attaching a needle to the pre-filled syringe; c) pinching a site on the abdomen of the subject; d) inserting the needle into the pinched site; e) pushing the plunger; and f) removing the needle from the pinched site, thereby administering the liquid pharmaceutical formulation comprising the FcRn antagonist and the hyaluronidase to the subject.

72. The method of any one of claims 66, 68, or 70, wherein the pre-filled syringe is placed atroom temperature for at least 30 minutes.

73. The method of any one of claim 66-71, wherein the pre-filled syringe is placed at roomtemperature for 30-60 minutes.

74. The method of claim 70 or 71, wherein the pre-filled syringe is removed from the containerand placed at room temperature for 30-60 minutes.

75. The method of any one of claims 66-74, wherein the site on the abdomen is on the belly ofthe subject.

76. The method of claim 75, wherein the site on the abdomen is at least two or three inchesaway from the navel of the subject.

77. The method of any one of claims 66-76, further comprising cleaning the site on the abdomenof the subject.

78. The method of claim 77, wherein the cleaning is done with an alcohol swab.

79. The method of any one of claims 66-78, wherein the needle is attached to the collar.134 BUSINESS.32923153.

180. The method of any one of claims 66-79, further comprising removing the needle cap fromthe needle after it is attached to the pre-filled syringe.

81. The method of any one of claims 66-80, wherein the needle is inserted into the pinched siteat a 45˚-90˚ angle.

82. The method of any one of claims 68-81, wherein the plunger is pushed until it stops.

83. The method of claim 82, wherein the plunger is pushed slowly.

84. The method of claim 83, wherein the plunger is pushed for no more than 30 seconds,optionally no more than 28 seconds, optionally no more than 25 seconds, optionally no more than 20 seconds, optionally no more than 15 seconds, or optionally no more than 10 seconds, at room temperature.

85. The method of claim 83 or 84, wherein the plunger is pushed for 10 seconds or greater,optionally 15 seconds or greater, optionally 18 seconds or greater, or optionally 20 seconds or greater, at room temperature.

86. The method of any one of claims 83-85, wherein the plunger is pushed for 20-30 secondsfrom when it is first pushed to when it stops.

87. The method of any one of claims 82-86, wherein the plunger stops when the stopper reachesthe distal end of the barrel of the pre-filled syringe.

88. The method of any one of claims 82-86, wherein the plunger stops when the thumb padcomes within 1 cm of the proximal end of the barrel of the pre-filled syringe.

89. The method of any one of claims 66-88, wherein the needle is removed at the same angle atwhich it was inserted. 135 BUSINESS.32923153.

190. The method of any one of claims 66-89, further comprising covering the needle afterremoving the needle.

91. The method of claim 90, wherein the needle is covered with a needle shield.

92. The method of any one of claims 66-91, further comprising pressing gauze over the pinchedsite after removing the needle.

93. The method of any one of claims 66-92, wherein the pre-filled syringe is stored at 2˚ C - 8˚C prior to being placed at room temperature.

94. The method of any one of claims 66-92, wherein the pre-filled syringe is stored at 20˚ C -30˚ C for up to 1 month.

95. The method of any one of claims 66-94, wherein the subject has myasthenia gravis.

96. The method of any one of claims 66-95, wherein the subject has generalized myastheniagravis.

97. The method of any one of claims 66-96, wherein the subject is anti-acetylcholine receptor(AChR) antibody positive.

98. The method of any one of claims 66-97, wherein the subject shows a statistically significantimprovement in MG-ADL responder rate after administration.

99. The method of any one of claims 66-98, wherein the subject that received administrationbelongs to a group of subjects that shows a significant improvement in MG-ADL responder rate after administration.

100. The method of any one of claims 66-99, wherein the subject shows reduction in erythema,swelling, and / or induration at the injection site in less than 30 minutes, optionally less than 45 136 BUSINESS.32923153.1minutes, optionally less than 60 minutes, optionally less than 75 minutes, or optionally less than 90 minutes.

101. The method of any one of claims 66-100, wherein the subject indicates no pain or mild painimmediately after the injection, optionally 5 minutes after the injection, or optionally 10 minutes after the injection.

102. The method of any one of claims 66-101, wherein the subject indicates that they would havethe injection again.

103. The method of any one of claims 66-102, wherein back leakage is minimal.

104. The method of claim 103, wherein back leakage is less than 15 μL, optionally less than 10μL, optionally less than 8 μL, or optionally less than 5 μL.

105. The method of any one of claims 66-104, wherein leakage is minimal.

106. The method of claim 105, wherein leakage is less than 25 μL, optionally leakage is less than20 μL, optionally leakage is less than 15 μL, optionally less than 10 μL, optionally less than 8 μL, or optionally less than 5 μL.

107. The method of any one of claims 66-106, wherein the pre-filled syringe containing the liquidpharmaceutical formulation comprising the FcRn antagonist and the hyaluronidase is an approved product.

108. The method of claim 107, wherein the approved product is approved for the treatment ofgMG in an adult.

109. The method of claim 107 or 108, wherein the adult is anti-AChR antibody positive.

110. The method of any one of claims 66-109, wherein administration of the liquidpharmaceutical formulation to the subject with the pre-filled syringe provides a dose of FcRn 137 BUSINESS.32923153.1antagonist and hyaluronidase bioequivalent to the same dose of the FcRn antagonist and hyaluronidase administered to a second subject using a second formulation administered in a syringe that is filled from a vial just prior to administration.

111. The method of any one of claims 66-109, wherein administration of the liquidpharmaceutical formulation to the subject with the pre-filled syringe provides a dose of FcRn antagonist and hyaluronidase with increased Cmaxand AUC when compared to the same dose of the FcRn antagonist and hyaluronidase administered to a second subject using a second formulation administered in a syringe that is filled from a vial just prior to administration.

112. A method of administering efgartigimod and hyaluronidase in a pre-filled syringe to asubject comprising discarding a first pre-filled syringe when the first pre-filled syringe is cracked, broken, or damaged; replacing the first pre-filled syringe with a second pre-filled syringe that is not cracked, broken, or damaged; and administering the efgartigimod and the hyaluronidase to the subject from the second pre-filled syringe.

113. The method of claim 112, wherein the first pre-filled syringe is missing a syringe cap.

114. A method of administering efgartigimod and hyaluronidase in a pre-filled syringe to asubject comprising discarding a first pre-filled syringe when the date of administration is after an expiration date of the first pre-filled syringe; replacing the first pre-filled syringe with a second pre- filled syringe when the date of administration is before an expiration date of the second pre-filled syringe; and administering the efgartigimod and the hyaluronidase to the subject from the second pre-filled syringe.

115. A method of administering efgartigimod and hyaluronidase in a pre-filled syringe to asubject comprising discarding a first pre-filled syringe when the efgartigimod and hyaluronidase inside the first pre-filled syringe are discolored and / or contains particles; replacing the first pre- filled syringe with a second pre-filled syringe wherein the efgartigimod and the hyaluronidase inside the second pre-filled syringe is not discolored and / or does not contain particles; and administering the efgartigimod and the hyaluronidase to the subject from the second pre-filled syringe. 138 BUSINESS.32923153.1116. The method of claim 115, wherein the efgartigimod and hyaluronidase inside the syringe arenot clear to light yellow in color.

117. The method of any one of claims 66-116, wherein the administration is performed onceweekly for 4 weeks.

118. A method of administering efgartigimod and hyaluronidase to a subject, the methodcomprising subcutaneously injecting the efgartigimod and hyaluronidase for a duration of administration of between 20 and 30 seconds.

119. An FcRn antagonist for use in a method of treating an autoimmune disease in a subject inneed thereof, wherein the FcRn antagonist is administered subcutaneously to the subject using a pre-filled syringe according to any one of claims 1-54.

120. An FcRn antagonist for use according to claim 119, wherein the method is in accordancewith any one of claims 58-110.

121. An FcRn antagonist for use according to claim 119 or 120, wherein the FcRn antagonist isadministered using the pre-filled syringe and the duration of administration is no more than 30 seconds, optionally no more than 28 seconds, or optionally no more than 25 seconds.

122. An FcRn antagonist for use according to any one of claims 119-121, wherein the FcRnantagonist is administered with the pre-filled syringe and the duration of administration is 15 seconds or greater, optionally 18 seconds or greater, or optionally 20 seconds or greater.

123. An FcRn antagonist for use according to any one of claims 119-122, wherein the FcRnantagonist is administered with the pre-filled syringe and the duration of administration is 20-30, 20-28, or 20-25 seconds.

124. An FcRn antagonist for use according to any one of claims 119-123, wherein the pre-filledsyringe is a part of a kit according to any of claims 55-65. 139 BUSINESS.32923153.1125. An FcRn antagonist for use according to any one of claims 119-124, wherein the pre-filledsyringe is placed at room temperature for at least 30 minutes prior to administration.

126. An FcRn antagonist for use according to any one of claims 119-125, wherein theautoimmune disease is myasthenia gravis.

127. Efgartigimod for use in a method of treating an autoimmune disease in a subject in needthereof, wherein the efgartigimod is administered to the subject by subcutaneous injection and the duration of administration is 20-30, 20-28, or 20-25 seconds.

128. Efgartigimod for use according to claim 127, wherein the efgartigimod is administered incombination with hyaluronidase.

129. Efgartigimod for use according to claim 127 or 128, wherein the autoimmune disease ismyasthenia gravis.

130. The method or use of any one of claims 66-129, wherein the liquid pharmaceuticalformulation or efgartigimod is administered by the subject to themselves.

131. A liquid pharmaceutical formulation comprising about 200 mg / mL efgartigimod, about2,000 U / mL rHuPH20, about 10.5 mg / mL L-arginine hydrochloride, about 1.4 mg / mL L-histidine, about 2.2 mg / mL L-histidine hydrochloride monohydrate, about 1.5 mg / mL L-methionine, about 0.4 mg / mL polysorbate 80, about 4.1 mg / mL sodium chloride, and about 20.5 mg / mL sucrose, at about pH 6.0.

132. A liquid pharmaceutical formulation comprising about 200 mg / mL efgartigimod, about2,000 U / mL rHuPH20, about 50 mM L-arginine, about 20 mM L-histidine, about 10 mM L- methionine, about 0.04% polysorbate 80, about 70 mM sodium chloride, and about 60 mM sucrose.

133. A liquid pharmaceutical formulation comprising about 200 mg / mL efgartigimod, about2,000 U / mL rHuPH20, about 50 mM L-arginine hydrochloride, about 20 mM L-histidine and L- 140 BUSINESS.32923153.1histidine hydrochloride monohydrate, about 10 mM L-methionine, about 0.04% polysorbate 80, about 70 mM sodium chloride, and about 60 mM sucrose.

134. A liquid pharmaceutical formulation comprising 200 mg / mL efgartigimod, 2,000 U / mLrHuPH20, 10.5 mg / mL L-arginine hydrochloride, 1.4 mg / mL L-histidine, 2.2 mg / mL L-histidine hydrochloride monohydrate, 1.5 mg / mL L-methionine, 0.4 mg / mL polysorbate 80, 4.1 mg / mL sodium chloride, and 20.5 mg / mL sucrose, at pH 6.0.

135. A liquid pharmaceutical formulation comprising 200 mg / mL efgartigimod, 2,000 U / mLrHuPH20, 50 mM L-arginine, 20 mM L-histidine, 10 mM L-methionine, 0.04% polysorbate 80, 70 mM sodium chloride, and 60 mM sucrose.

136. A liquid pharmaceutical formulation comprising 200 mg / mL efgartigimod, 2,000 U / mLrHuPH20, 50 mM L-arginine hydrochloride, 20 mM L-histidine and L-histidine hydrochloride monohydrate, 10 mM L-methionine, 0.04% polysorbate 80, 70 mM sodium chloride, and 60 mM sucrose.

137. A method of treating gMG in a subject in need thereof comprising administering to thesubject the liquid pharmaceutical formulation of any one of claims 1-65 or 131-136.

138. The method of claim 137, wherein the subject is an adult.

139. The method of claim 137 or 138, wherein the adult is anti-AChR antibody positive.

140. The method of any one of claims 137-139, wherein the administration is performed onceweekly for 4 weeks.

141. Efgartigimod for use in treating gMG, wherein the efgartigimod is contained in the liquidpharmaceutical formulation of any one of claims 1-65 or 131-136.

142. Efgartigimod for the use of claim 141, wherein the subject is an adult.141 BUSINESS.32923153.1143. Efgartigimod for the use of claim 141 or 142, wherein the adult is anti-AChR antibodypositive.

144. Efgartigimod for the use of any one of claims 141-143, wherein the administration isperformed once weekly for 4 weeks.

145. An approved product comprising a pre-filled syringe containing a liquid pharmaceuticalformulation comprising a human neonatal Fc receptor (FcRn) antagonist and a hyaluronidase, wherein the FcRn antagonist is efgartigimod.

146. The approved product of claim 145, wherein the hyaluronidase comprises recombinanthuman PH20 (rHuPH20).

147. The approved product of claim 145 or 146, wherein the liquid pharmaceutical formulationcomprises 1000 mg of efgartigimod148. The approved product of any one of claims 145-147, wherein the liquid pharmaceuticalformulation comprises 200 mg / mL of efgartigimod.

149. The approved product of any one of claims 145-148, wherein the liquid pharmaceuticalformulation comprises 10,000 Units of the hyaluronidase.

150. The approved product of any one of claims 145-149, wherein the liquid pharmaceuticalformulation comprises 2,000 Units / mL of the hyaluronidase.

151. The approved product of any one of claims 145-150, wherein the liquid pharmaceuticalformulation comprises 10,000 Units of rHuPH20.

152. The approved product of any one of claims 145-151, wherein the liquid pharmaceuticalformulation comprises 2,000 Units / mL of rHuPH20. 142 BUSINESS.32923153.1153. The approved product of any one of claims 145-152, wherein the liquid pharmaceuticalformulation comprises 200 mg / mL efgartigimod, 2000 U / mL rHuPH20, 10.5 mg / mL L-arginine hydrochloride, 1.4 mg / mL L-histidine, 2.2 mg / mL L-histidine hydrochloride monohydrate, 1.5 mg / mL L-methionine, 0.4 mg / mL polysorbate 80, 4.1 mg / mL sodium chloride, 20.5 mg sucrose, and water for injection, USP, at a pH of 6.0.

154. A method of treating gMG in a subject in need thereof comprising administering to thesubject the approved product of any one of claims 145-153.

155. The method of claim 154, wherein the patient is anti-AChR antibody positive.

156. The approved product of any one of claims 145-153 for use in a method of treating gMG ina subject in need thereof.

157. The approved product of claim 156, wherein the patient is anti-AChR antibody positive.143 BUSINESS.32923153.1

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