Subcutaneous formulations of Anti-CD20 antibody

Abstract

Provided herein are subcutaneous formulations of anti-CD20 antibody proteins, and methods of using the same for the treatment of autoimmune diseases, e.g., multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and myasthenia gravis (MG), among others.

Description

Attorney Docket No.50581-0016WO1 SUBCUTANEOUS FORMULATIONS OF ANTI-CD20 ANTIBODY 1. CLAIM OF PRIORITY

[0001] This application claims the benefit of U.S. Provisional Application Serial No. 63 / 566,707, filed on March 18, 2024. The entire contents of the foregoing are hereby incorporated by reference. 2. REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0002] This application contains a Sequence Listing that has been submitted electronically as an XML file named “50581-0016WO1.XML.” The XML file, created on March 12, 2025, is 39,374 bytes in size. The material in the XML file is hereby incorporated by reference in its entirety. 3. FIELD OF THE DISCLOSURE

[0003] The present disclosure is in the field of subcutaneous formulations of recombinant anti-CD20 antibodies, methods of producing such formulations, and uses of such formulations. 4. BACKGROUND OF THE DISCLOSURE

[0004] Anti-CD20 antibodies have been shown to be, or have the potential to be, therapeutically effective in the treatment of a number of autoimmune diseases, including multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and myasthenia gravis (MG), among others. 5. SUMMARY OF THE DISCLOSURE

[0005] Provided herein are methods for treating an autoimmune disease in a human subject comprising: a) subcutaneously administering to the human subject on day 1, a first dose comprising about 50 mg, about 100 mg, about 150 mg, about 225 mg, about 300 mg, or about 400 mg of a population of anti-CD20 antibody proteins, b) intravenously administering to the human subject at about 2 weeks after the first dose, a second dose comprising about 450 mg of the population of anti-CD20 antibody proteins, c) intravenously administering to the human subject at about 6 months after the first dose, a third dose comprising about 450 mg of the population of anti-CD20 antibody proteins, and d) intravenously administering to the humanAttorney Docket No.50581-0016WO1 subject at about 6 months after the prior dose, one or more subsequent doses comprising about 450 mg of the population of anti-CD20 antibody proteins. Preferably, the anti-CD20 antibody proteins in the population comprise: a) a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2, or b) a heavy chain variable region (VH) comprising a VH complementarity determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO:3, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:5; and a light chain variable region (VL) comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:8, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:9, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:10. Preferably, the population of anti-CD20 antibody proteins has an N-glycan profile comprising 10 to 20% galactosylated glycans and about 20 to 40% fucosylated glycans. Preferably, the anti-CD20 antibody proteins are ublituximab.

[0006] Also provided herein are methods for treating an autoimmune disease in a human subject comprising: a) subcutaneously administering to the human subject on day 1, a first dose comprising a population of anti-CD20 antibody proteins in an amount bioequivalent to about 150 mg of the population of anti-CD20 antibody proteins administered intravenously, b) subcutaneously administering to the human subject at about 2 weeks after the first dose, a second dose comprising the population of anti-CD20 antibody proteins in an amount bioequivalent to about 225 mg of the population of anti-CD20 antibody proteins administered intravenously, c) subcutaneously administering to the human subject at about 12 weeks after the first dose, a third dose comprising the population of anti-CD20 antibody proteins in an amount bioequivalent to about 225 mg of the population of anti-CD20 antibody proteins administered intravenously, and d) subcutaneously administering to the human subject at about 12 weeks after the prior dose, one or more subsequent doses comprising the population of anti-CD20 antibody proteins in an amount bioequivalent to about 225 mg of the population of anti-CD20 antibody proteins administered intravenously. Preferably, the anti-CD20 antibody proteins in the population comprise: a) a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2, or b) a heavy chain variable region (VH) comprising a VH complementarity determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO:3, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:4,Attorney Docket No.50581-0016WO1 and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:5; and a light chain variable region (VL) comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:8, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:9, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:10. Preferably, the population of anti-CD20 antibody proteins has an N-glycan profile comprising 10 to 20% galactosylated glycans and about 20 to 40% fucosylated glycans. Preferably, the anti-CD20 antibody proteins are ublituximab.

[0007] Also provided herein are methods for treating an autoimmune disease in a human subject comprising: a) subcutaneously administering to the human subject on day 1, a first dose comprising a population of anti-CD20 antibody proteins in an amount bioequivalent to about 150 mg of the population of anti-CD20 antibody proteins administered intravenously, b) subcutaneously administering to the human subject at about 2 weeks after the first dose, a second dose comprising the population of anti-CD20 antibody proteins in an amount bioequivalent to about 150 mg of the population of anti-CD20 antibody proteins administered intravenously, c) subcutaneously administering to the human subject at about 8 weeks after the first dose, a third dose comprising the population of anti-CD20 antibody proteins in an amount bioequivalent to about 150 mg of the population of anti-CD20 antibody proteins administered intravenously, and d) subcutaneously administering to the human subject at about 8 weeks after the prior dose, one or more subsequent doses comprising the population of anti-CD20 antibody proteins in an amount bioequivalent to about 150 mg of the population of anti-CD20 antibody proteins administered intravenously. Preferably, the anti-CD20 antibody proteins in the population comprise: a) a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2, or b) a heavy chain variable region (VH) comprising a VH complementarity determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO:3, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:5; and a light chain variable region (VL) comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:8, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:9, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:10. Preferably the population of anti-CD20 antibody proteins has an N-glycan profile comprising 10 to 20% galactosylated glycans andAttorney Docket No.50581-0016WO1 about 20 to 40% fucosylated glycans. Preferably, the anti-CD20 antibody proteins are ublituximab.

[0008] In some embodiments, the autoimmune disease is multiple sclerosis (MS). In some embodiments, the MS is a relapsing form of MS (RMS). In some embodiments, the RMS is selected from clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS) and active secondary progressive MS SPMS). In some embodiments, the subject has an Expanded Disability Status Scale (EDSS) score of from 0 to 5.5 prior to treatment. In some embodiments, the subject is diagnosed with RMS in accordance to 2017 Revised McDonald Criteria.

[0009] In some embodiments, the autoimmune disease is rheumatoid arthritis (RA). In some embodiments, the autoimmune disease is lupus. In some embodiments, the autoimmune disease is myasthenia gravis (MG). In some embodiments, the autoimmune disease is chronic idiopathic demyelinating polyneuropathy (CIDP).

[0010] In some embodiments, the first dose comprises about 50 mg of the population of anti- CD20 antibody proteins. In some embodiments, the first dose comprises about 100 mg of the population of anti-CD20 antibody proteins. In some embodiments, the first dose comprises about 150 mg of the anti-CD20 antibody proteins. In some embodiments, the first dose comprises about 225 mg of the anti-CD20 antibody proteins. In some embodiments, the first dose comprises about 300 mg of the anti-CD20 antibody proteins. In some embodiments, the first dose comprises about 400 mg of the anti-CD20 antibody proteins.

[0011] In some embodiments, the first dose is administered from a single use vial or a pre- filled syringe that comprises a pharmaceutical formulation comprising about 150 mg / ml of the anti-CD20 antibody proteins. In some embodiments, the first dose is split over multiple administrations. In some embodiments, the multiple administrations occur at multiple sites on the human subject’s body. In some embodiments, the first dose is administered to the subject by a healthcare professional or is self-administered by the subject.

[0012] In some embodiments, each of the second dose, the third dose, and the one or more subsequent doses is administered from a single use vial that comprises a pharmaceutical formulation comprising about 50 mg / ml to 150 mg / ml of the anti-CD20 antibody proteins. In some embodiments, each of the second dose, the third dose, and the one or more subsequent doses is administered by intravenous infusion over 1 hour.Attorney Docket No.50581-0016WO1

[0013] In some embodiments, the first dose comprises about 265 mg – 450 mg of the population of anti-CD20 antibody proteins. In some embodiments, the first dose comprises about 400 mg of the population of anti-CD20 antibody proteins.

[0014] In some embodiments, each of the second dose, the third dose, and the one or more subsequent doses comprises about 265 mg - 450 mg of the population of anti-CD20 antibody proteins. In some embodiments, each of the second dose, the third dose, and the one or more subsequent doses comprises about 400 mg of the population of anti-CD20 antibody proteins.

[0015] In some embodiments, the subject has been pre-medicated with a dosage of a corticosteroid 30-60 minutes prior to administration of the population of anti-CD20 antibody proteins. In some embodiments, the dosage of the corticosteroid is about 100 mg methylprednisone or 10-20 mg dexamethasone.

[0016] In some embodiments, the subject has been pre-medicated with a dosage of an antihistamine 30-60 minutes prior to administration of the population of anti-CD20 antibody proteins. In some embodiments, the dosage of the antihistamine is about 25 to 50 mg diphenhydramine HCl.

[0017] In some embodiments, the subject has been pre-medicated with an antipyretic 30-60 minutes prior to administration of the composition comprising a population of anti-CD20 antibody proteins. In some embodiments, the antipyretic is acetaminophen or an antipyretic bioequivalent thereto.

[0018] In some embodiments, a pharmaceutical formulation comprising about 50 mg / mL to 150 mg / mL of the population of anti-CD20 antibody proteins is administered to the subject. In some embodiments, the pharmaceutical formulation comprises about 150 mg / mL of the population of anti-CD20 antibody proteins. In some embodiments, the pharmaceutical formulation further comprises one or more of the following: sodium chloride, sodium citrate, polysorbate 80, and hydrochloric acid. In some embodiments, the pharmaceutical formulation comprises 8-10 mg / mL of sodium chloride. In some embodiments, the pharmaceutical formulation comprises 9.0 mg / mL of sodium chloride. In some embodiments, the pharmaceutical formulation comprises 7-8 mg / mL of sodium citrate. In some embodiments, the pharmaceutical formulation comprises 7.4 mg / mL of sodium citrate. In some embodiments, the pharmaceutical formulation comprises 0.5-0.8 mg / mL of polysorbate 80. In some embodiments, the pharmaceutical formulation comprises 0.7 mg / mL of polysorbate 80. In some embodiments,Attorney Docket No.50581-0016WO1 the pharmaceutical formulation comprises 0.3-0.5 mg / mL of hydrochloric acid. In some embodiments, the pharmaceutical formulation comprises 0.4 mg / mL of hydrochloric acid. In some embodiments, the pharmaceutical formulation comprises 20-30 mM sodium citrate. In some embodiments, the pharmaceutical formulation comprises 25 mM sodium citrate. In some embodiments, the pharmaceutical formulation comprises 125-160 mM sodium chloride. In some embodiments, the pharmaceutical formulation comprises 154 mM sodium chloride. In some embodiments, the pharmaceutical formulation comprises 0.05%-0.1% polysorbate 80. In some embodiments, the pharmaceutical formulation comprises 0.07% polysorbate 80. In some embodiments, the pharmaceutical formulation has a pH of 6-7. In some embodiments, the pharmaceutical formulation has a pH of 6.5.

[0019] Also provided herein are single use vials or pre-filled syringes comprising a pharmaceutical formulation comprising about 50 mg / mL to 150 mg / mL of a population of anti- CD20 antibody proteins, wherein the anti-CD20 antibody protein in the population comprises: a) a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2, or b) a heavy chain variable region (VH) comprising a VH complementarity determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO:3, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:5; and a light chain variable region (VL) comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:8, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:9, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:10. Preferably, the population of anti-CD20 antibody proteins has an N-glycan profile comprising 10 to 20% galactosylated glycans and about 20 to 40% fucosylated glycans. Preferably, the anti-CD20 antibody proteins are ublituximab.

[0020] In some embodiments, the single use vials or pre-filled syringes comprise about 150 mg / mL of the population of anti-CD20 antibody proteins. In some embodiments, the single use vials or pre-filled syringes comprise the population of anti-CD20 antibody proteins in a volume of 1 mL to 3.5 mL. In some embodiments, the single use vials or pre-filled syringes comprise the population of anti-CD20 antibody proteins in a volume of about 2 mL.

[0021] In some embodiments, the pharmaceutical formulation further comprises one or more of the following: sodium chloride, sodium citrate, polysorbate 80, and hydrochloric acid. InAttorney Docket No.50581-0016WO1 some embodiments, the pharmaceutical formulation comprises about 8 to about 10 mg / mL of sodium chloride. In some embodiments, the pharmaceutical formulation comprises 9.0 mg / mL of sodium chloride. In some embodiments, the pharmaceutical formulation comprises about 7 to about 8 mg / mL of sodium citrate. In some embodiments, the pharmaceutical formulation comprises 7.4 mg / mL of sodium citrate. In some embodiments, the pharmaceutical formulation comprises about 0.5 to about 0.8 mg / mL of polysorbate 80. In some embodiments, the pharmaceutical formulation comprises 0.7 mg / mL of polysorbate 80. In some embodiments, the pharmaceutical formulation comprises about 0.3 to about 0.5 mg / mL of hydrochloric acid. In some embodiments, the pharmaceutical formulation comprises 0.4 mg / mL of hydrochloric acid. In some embodiments, the pharmaceutical formulation comprises about 20 to about 30 mM sodium citrate. In some embodiments, the pharmaceutical formulation comprises 25 mM sodium citrate. In some embodiments, the pharmaceutical formulation comprises about 125 to about 160 mM sodium chloride. In some embodiments, the pharmaceutical formulation comprises 154 mM sodium chloride. In some embodiments, the pharmaceutical formulation comprises about 0.05% to about 0.1% polysorbate 80. In some embodiments, the pharmaceutical formulation comprises 0.07% polysorbate 80. In some embodiments, the pharmaceutical formulation has a pH of about 6 to about 7. In some embodiments, the pharmaceutical formulation has a pH of 6.5.

[0022] In some embodiments, the anti-CD20 antibody proteins of the population are present in a single dosage form.

[0023] In some embodiments, the single use vials or pre-filled syringes are for use in the methods described herein.

[0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Methods and materials are described herein for use in the present invention; other, suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control.

[0025] Other features and advantages of the invention will be apparent from the following detailed description and figures, and from the claims.Attorney Docket No.50581-0016WO1 6. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 illustrates the structure and abbreviations for various N-glycans.

[0027] Figure 2 illustrates the glycosylation profile of a sample of anti-CD20 antibody proteins provided herein.

[0028] Figure 3 illustrates the intact MS Spectra of a sample of anti-CD20 antibody proteins provided herein.

[0029] Figure 4 depicts the expression vector map, HK463-25, containing the immunoglobulin heavy and light chain cDNA sequences of source anti-CD20 antibody, TG- 1101, described herein.

[0030] Figure 5 provides a flow diagram with an overview of the manufacturing process for TG- 1101.

[0031] Figure 6 provides graphs showing the concentration of ublituximab administered in Cohorts SC1 - SC5 over 15 days (time 0hr to 400hr).

[0032] Figure 7 provides graphs showing dose-normalized concentration of ublituximab administered in Cohorts SC1 - SC5 and IV over 15 days (time 0hr to 400hr).

[0033] Figure 8 is a graph showing ublituximab viscosity as a function of concentration. 7. DETAILED DESCRIPTION OF THE DISCLOSURE

[0034] Provided herein are subcutaneous formulations comprising populations of anti-CD20 antibody proteins. In particular, the present disclosure provides formulations of anti-CD20 antibody proteins that are suitable for subcutaneous administration. Also disclosed herein are methods for using such formulations, alone or in combination with formulations of anti-CD20 antibody proteins that are suitable for intravenous administration.

[0035] Preferably, the anti-CD20 antibody used in the present compositions and methods is ublituximab, a monoclonal antibody that targets epitopes on CD20, e.g., IRAHT (SEQ ID NO: 37), and EPAN (SEQ ID NO: 38). See, Fox, E. et al., Mult. Scler.27:420-429 (March 2021); Babiker et al., Expert Opin Investig Drugs 27:407-412 (2018); Cotchett, KR et al., Multiple Sclerosis and Related Disorders 49:102787 (2021); Miller et al., Blood 120:Abstract No.2756 (2012); Deng, C. et. al., J. Clin. Oncol.31:Abstract No. 8575 (2013). TG-1101 is also described in U.S. Patent Nos. 9,234,045 and 9,873,745. Ublituximab (TG Therapeutics, Inc.) (also knownAttorney Docket No.50581-0016WO1 as UBX, UTX, TG-1101, TGTX-1101, UTUXINTM, LFB-R603, TG20, EMAB603, BRIUMVI®) can preferably have a unique N-glycan profile profile comprising 10 to 20% galactosylated glycans and about 20 to 40% fucosylated glycans, e.g., a profile as shown in Figure 1, that is produced as described in WO 2023 / 235764 and WO 2023 / 235762, the entire contents of which are incorporated herein by reference. 7.1 Abbreviations and Conventions

[0036] The following abbreviations are used throughout this application.Attorney Docket No.50581-0016WO17.2 Definitions

[0037] As used herein, the term “population of anti-CD20 antibody proteins” refers to a composition comprising a plurality anti-CD20 antibody proteins. The individual anti-CD20 antibody proteins in a population can comprise similar or different post-translationalAttorney Docket No.50581-0016WO1 modifications, e.g., as described in detail in WO 2023 / 235764, which is incorporated herein by reference in its entirety. The population of anti-CD20 antibody proteins can refer to all anti- CD20 antibody proteins that are present in a single dosage form or present in a single batch.

[0038] As used herein, the term “single batch” in the context of anti-CD20 antibody proteins refers to a composition derived from a single production or run from a single bioreactor of a specified volume. For example, the anti-CD20 antibody proteins obtained from a single run of a 10,000 L bioreactor, a 15,000 L bioreactor, a 20,000 L bioreactor, or a 25,000 L bioreactor can be referred to as a single batch. In certain embodiments, the bioreactor has a capacity of at least 100 L; at least 200 L; at least 300 L; at least 400 L; at least 500 L; at least 750 L; at least 1,000 L; at least 2,000 L; at least 3,000 L; at least 4,000 L; at least 5,000 L; at least 7,500 L; at least 10,000 L; at least 15,000 L; at least 20,000 L; or at least 25,000 L.

[0039] As used herein, and unless otherwise specified, the term “about” or “approximately” means an acceptable error for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined. Unless otherwise defined, the term “about” or “approximately” means within + / - 10% of a given value or range. 7.3 Primary Amino Acid Sequence of the Anti-CD20 Antibody

[0040] The anti-CD20 antibody proteins provided herein can be expressed from one or more nucleic acid sequences encoding a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2. The anti-CD20 antibody proteins described herein can be a population of anti-CD20 antibody proteins, wherein the anti-CD20 antibody proteins in the population comprise: a heavy chain variable region (VH) comprising a VH complementarity determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO:3, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:5; and / or a light chain variable region (VL) comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:8, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:9, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:10. Sequences are provided below in the Sequence Table.

[0041] The anti-CD20 antibody proteins (e.g., anti-CD20 antibody proteins in a population of anti-CD20 antibody proteins) provided herein can be expressed from one or more nucleic acidAttorney Docket No.50581-0016WO1 sequences encoding a heavy chain comprising the amino acid sequence of SEQ ID NO:1 or an amino acid that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to SEQ ID NO:1; and a light chain comprising the amino acid sequence of SEQ ID NO:2 or an amino acid that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to SEQ ID NO:2. The anti-CD20 antibody proteins (e.g., anti-CD20 antibody proteins in a population of anti-CD20 antibody proteins) can comprise a heavy chain comprising the amino acid sequence of SEQ ID NO:1 or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to SEQ ID NO:1; and / or a light chain comprising the amino acid sequence of SEQ ID NO:2 or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to SEQ ID NO:2.

[0042] The anti-CD20 antibody proteins (e.g., anti-CD20 antibody proteins in a population of anti-CD20 antibody proteins) provided herein can comprise the VH of SEQ ID NO:6 and / or the VL of SEQ ID NO:11. In some embodiments, the anti-CD20 antibody proteins (e.g., anti- CD20 antibody proteins in a population of anti-CD20 antibody proteins) comprise a VH comprising the amino acid sequence of SEQ ID NO:6 or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to SEQ ID NO:6; and / or a VL comprising the amino acid sequence of SEQ ID NO:11 or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to SEQ ID NO:11.

[0043] The anti-CD20 antibody proteins (e.g., anti-CD20 antibody proteins in a population of anti-CD20 antibody proteins) provided herein can comprise a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:3, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to SEQ ID NO:3; a VH CDR2 comprising the amino acid sequence of SEQ ID NO:4, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to SEQ ID NO:4; and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:5 or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to SEQ ID NO:5. The anti-CD20 antibody proteins (e.g., anti-CD20 antibody proteins in a population of anti-CD20 antibody proteins) provided herein can comprise a VL comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:8 or an amino acid sequence thatAttorney Docket No.50581-0016WO1 is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to SEQ ID NO:8; a VL CDR2 comprising the amino acid sequence of SEQ ID NO:9 or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to SEQ ID NO:9; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:10 or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or at least 99% identical to SEQ ID NO:10.

[0044] The one or more nucleic acid sequences encoding the heavy chain of the anti-CD20 antibody proteins provided herein can comprise the nucleic acid sequence of SEQ ID NO:35. The one or more nucleic acid sequence encoding the light chain of the anti-CD20 antibody proteins provided herein can comprise the nucleic acid sequence of SEQ ID NO:36.

[0045] The anti-CD20 antibody proteins (e.g., anti-CD20 antibody proteins in a population of anti-CD20 antibody proteins) provided herein can be chimeric immunoglobulin G1 (IgG1) anti-CD20 monoclonal antibody proteins, each comprised of a tetrameric assembly from two light chains (213 amino acids) and two heavy chains (448 amino acids).

[0046] The anti-CD20 antibody proteins (e.g., anti-CD20 antibody proteins in a population of anti-CD20 antibody proteins) provided herein can be expressed from one or more nucleic acid sequences encoding a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2 and comprise a pyroglutamate at position 1 of light chain and / or heavy chain instead of glutamine, thus resulting in an amino acid sequence of SEQ ID NO:13 for the heavy chain and / or an amino acid sequence of SEQ ID NO:14 for the light chain. The anti-CD20 antibody proteins (e.g., anti-CD20 antibody proteins in a population of anti-CD20 antibody proteins) provided herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2 and comprise a pyroglutamate at position 1 of light chain and / or heavy chain instead of glutamine, thus resulting in an amino acid sequence of SEQ ID NO:13 for the heavy chain and / or an amino acid sequence of SEQ ID NO:14 for the light chain.

[0047] The anti-CD20 antibody proteins (e.g., anti-CD20 antibody proteins in a population of anti-CD20 antibody proteins) provided herein can be expressed from one or more nucleic acid sequences encoding a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2 and comprise a deletion of the C-terminal lysine at the heavy chain thus resulting in the amino acid sequence of SEQ IDAttorney Docket No.50581-0016WO1 NO:15.The anti-CD20 antibody proteins (e.g., anti-CD20 antibody proteins in a population of anti-CD20 antibody proteins) provided herein can comprise a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2 and comprise a deletion of the C-terminal lysine at the heavy chain thus resulting in the amino acid sequence of SEQ ID NO:15.

[0048] Thus, provided herein is a composition or population of anti-CD20 antibody proteins wherein at least 50%, 60%, 70%, 80%, 90%, 95%, or 98% comprises (i) a pyroglutamate at position 1 (instead of glutamine) of the heavy chain, (ii) a pyroglutamate at position 1 (instead of glutamine) of the light chain, and / or (iii) a deletion of the C-terminal lysine of the heavy chain. For example, provided herein is a composition or population of anti-CD20 antibody proteins wherein at least 50%, 60%, 70%, 80%, 90%, 95%, or 98% comprises (i) a pyroglutamate at position 1 (instead of glutamine) of the heavy chain, e.g., a heavy chain comprising the amino acid sequence of SEQ ID NO:13, (ii) a pyroglutamate at position 1 (instead of glutamine) of the light chain, e.g., a light chain comprising the amino acid sequence of SEQ ID NO:14, and / or (iii) a deletion of the C-terminal lysine of the heavy chain, e.g., a heavy chain comprising the amino acid sequence of SEQ ID NO:15.

[0049] An anti-CD20 antibody protein useful in the present compositions and methods can be expressed from one or more nucleic acid sequences encoding a light chain comprising the amino acid sequence of SEQ ID NO:16. An anti-CD20 antibody protein (e.g., an anti-CD20 antibody protein in a population of anti-CD20 antibody proteins) can comprise a light chain comprising the amino acid sequence of SEQ ID NO:16. As one example, the anti-CD20 antibodies can comprise a light chain comprising the amino acid sequence of SEQ ID NO:16, and a heavy chain comprising the amino acid sequence of SEQ ID NO:15. 7.4 Anti-CD20 Antibody Protein Compositions

[0050] The anti-CD20 antibody protein compositions provided herein can be described by various post-translational modifications and / or by their three-dimensional conformation. The respective levels of the various post-translational modifications can be quantified by means that are well known in the art. Without being bound by theory, these structural properties of the anti- CD20 antibody protein compositions provided herein can result in the biological and clinical properties of the protein compositions.Attorney Docket No.50581-0016WO1

[0051] The anti-CD20 antibody protein compositions produced in vitro have various post- translational modifications. It is understood that each individual anti-CD20 antibody protein may have its own specific pattern of post-translational modifications. To describe the properties of a population of multiple anti-CD20 antibody proteins, the overall presence of a specific post- translational modification can be quantified. Without being bound by theory, the levels of a specific post-translational modification in a population of anti-CD20 proteins can determine the biological and clinical properties of the composition (such as a dose of a pharmaceutical formulation). Without being bound by theory, the post-translational modifications are rendered by expression in a rat hybridoma cell (e.g., YB2 / 0 cell) in cell culture under the conditions described in WO 2023 / 235762, the entire contents of which are incorporated herein by reference.

[0052] In certain embodiments, a type of post-translational modification that can be used to describe the anti-CD20 antibody protein compositions provided herein is glycosylation. Various glycosylations are known and are described in detail in WO 2023 / 235764, which is incorporated herein by reference in its entirety. For example, the population of anti-CD20 antibody proteins described herein can have a glycosylation profile as described in WO 2023 / 235764, which is incorporated herein by reference in its entirety. In some embodiments, the glycosylation is N- glycosylation. N-glycans that can be present can be any one of the N-glycans shown in Figure 1. For example, the population of anti-CD20 antibody proteins described herein can have an N- glycan profile comprising about 10 to 20% galactosylated glycans and about 20 to 40% fucosylated glycans. Levels of N-glycosylation can be quantified using assays that are well known in the art.

[0053] In certain embodiments, a type of post-translational modification that can be used to describe the anti-CD20 antibody protein compositions provided herein is deamidation. Deamidation is a chemical reaction in which an amide functional group in the side chain of the amino acid asparagine or glutamine is removed or converted to another functional group. Typically, asparagine is converted to aspartic acid or isoaspartic acid. Levels of deamidation at a specific amino acid position in the anti-CD20 antibody protein compositions can be determined using assays that are well known in the art.

[0054] Assays for determining the amount of post-translational modifications in a population of antibody proteins (e.g., such as an anti-CD20 antibody population as described herein) are well known in the art. Assays can be used to determine the amount of one or more of asparagineAttorney Docket No.50581-0016WO1 deamidation, methionine oxidation, glycosylation, pyroglutamate formation, and lysine truncation. Assays are described in detail in WO 2023 / 235764, which is incorporated herein by reference in its entirety. Total protein

[0055] The amount of total protein in the compositions described herein can be measured, e.g., using spectrophotometry. For example, the amount of total protein can be measured by absorbance at 280 nm, e.g., by using methods described in WO 2023 / 235764, the entire contents of which are incorporated herein by reference.

[0056] The population of anti-CD20 antibody proteins provided herein can have an amount of total protein of about 25 mg / mL to 180 mg / mL (e.g., about 25 mg / mL to 170 mg / mL; about 25 mg / mL to 160 mg / mL; about 25 mg / mL to 150 mg / mL; about 50 mg / mL to 150 mg / mL; about 75 mg / mL to 150 mg / mL; about 100 mg / mL to 150 mg / mL; or about 125 mg / mL to 150 mg / mL (e.g., about 25 mg / mL; about 50 mg / mL; about 100 mg / mL; about 125 mg / mL; about 150 mg / mL; about 160 mg / mL; about 170 mg / mL; or about 180 mg / mL)). Preferably, the population can have an amount of total protein of about 150 mg / mL. Alternatively, the population can have an amount of total protein of about 25 mg / mL. 7.5 Biological Properties

[0057] The populations of anti-CD20 antibody proteins provided herein can possess biological properties that are described in detail in WO 2023 / 235764, which is incorporated herein by reference in its entirety. Assays for measuring these biological properties are also described in WO 2023 / 235764 (incorporated herein by reference in its entirety). 7.6 Methods of Treating and Preventing Medical Conditions

[0058] Also provided herein are methods for treating and / or preventing one or more medical conditions in a subject (e.g., a human subject, such as, a patient) in need thereof, by subcutaneously administering to the subject the anti-CD20 antibody proteins described herein. In some embodiments, the subject has not been previously treated with an anti-CD20 antibody, or has not been treated with an anti-CD20 antibody within the preceding 6 or 12 months.Attorney Docket No.50581-0016WO1

[0059] For example, the methods can comprise subcutaneously administering to the subject at least1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more doses of the subcutaneous anti-CD20 antibody protein compositions described herein. In some instances, the subcutaneous anti-CD20 antibody protein composition is administered subcutaneously to the subject at Day 1, and optionally at one or more of Day 1, Day 15, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, and every 12 weeks (or about 3 months) thereafter. In some instances, the subcutaneous anti-CD20 antibody protein composition is administered subcutaneously to the subject at Day 1, and optionally at one or more of Day 1, Day 15, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56, Week 64, Week 72, Week 80, Week 88, Week 96 and every 8 weeks (or about 2 months) thereafter. Subcutaneous Administration

[0060] The present methods can comprise subcutaneously administering to the subject at least one dose of a subcutaneous formuation of the anti-CD20 antibody protein composition described herein, i.e., an anti-CD20 antibody protein composition described here is administered to a subject by subcutaneous injection. In some embodiments, about 200 mg to about 500 mg (e.g., about 200 mg to about 250 mg, about 250 mg to about 300 mg, about 300 mg to about 350 mg, about 350 mg to about 400 mg, about 400 mg to about 450 mg, about 450 mg to about 500 mg, about 200 mg to about 300 mg, about 200 mg to about 400 mg, about 200 mg to about 500 mg, about 300 mg to about 500 mg, about 250 mg to about 350 mg, about 300 mg to about 400 mg, about 350 mg to about 450 mg, or about 400 mg to about 500 mg (such as, about 200 mg, about 225 mg, about 250 mg, about 265 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, about 425 mg, about 450 mg, about 475 mg, or about 500 mg)) of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, in a volume of about 1-3.5 mL, e.g., 1-3 mL, 1-2.5 mL, or 1-2 mL (e.g., in a volume of about 1 mL, 1.5 mL, 2 mL, 2.5 mL, 3 mL, or 3.5 mL (such as, in a volume of about 2 mL)). For example, about 250 mg to about 500 mg (e.g., about 265 mg to about 450 mg, about 275 mg to about 425 mg, or about 300 mg to about 400 mg (such as, about 250 mg, about 255 mg, about 260 mg, about 265 mg, about 270 mg, about 275 mg, about 280 mg, about 285 mg, about 290 mg, about 295 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, about 425 mg, about 450 mg, about 475 mg, or about 500 mg)) of the anti-CD20Attorney Docket No.50581-0016WO1 antibody protein composition can be administered to a subject by subcutaneous injection. In some instances, about 265 mg to about 450 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. In some instances, about 200 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. In some instances, about 250 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. In some instances, about 225 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. In some instances, about 250 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. In some instances, about 265 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. In some instances, about 300 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. In some instances, about 350 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. In some instances, about 400 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. In some instances, about 450 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. In some instances, about 500 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. Preferably, the subcutaneous composition is administered in a volume of about 1-2 mL, preferably in a single injection, optionally in two injections administered consecutively. The subcutaneous injection can be administered to the subject by a healthcare professional (e.g., a physician, a nurse practitioner, a nurse, a physician assistant, a nursing assistant, and / or a medical assistant); and / or the subcutaneous injection can be self-administered by the subject.

[0061] A pharmaceutical formulation comprising anti-CD20 antibody proteins at a concentration of about 150 mg / mL can be administered to a subject by subcutaneous injection. For example, for administering about 200 mg of the anti-CD20 antibody protein composition to a subject, about 1.33 mL of a pharmaceutical formulation comprising anti-CD20 antibody proteins at a concentration of about 150 mg / mL can be administered to the subject by subcutaneous injection. For administering about 225 mg of the anti-CD20 antibody protein composition to a subject, about 1.5 mL of a pharmaceutical formulation comprising anti-CD20 antibody proteins at a concentration of about 150 mg / mL can be administered to the subject by subcutaneousAttorney Docket No.50581-0016WO1 injection. For administering about 250 mg of the anti-CD20 antibody protein composition to a subject, about 1.66 mL of a pharmaceutical formulation comprising anti-CD20 antibody proteins at a concentration of about 150 mg / mL can be administered to the subject by subcutaneous injection. For administering about 265 mg of the anti-CD20 antibody protein composition to a subject, about 1.76 mL of a pharmaceutical formulation comprising anti-CD20 antibody proteins at a concentration of about 150 mg / mL can be administered to the subject by subcutaneous injection. For administering about 300 mg of the anti-CD20 antibody protein composition to a subject, about 2.0 mL of a pharmaceutical formulation comprising anti-CD20 antibody proteins at a concentration of about 150 mg / mL can be administered to the subject by subcutaneous injection. For administering about 350 mg of the anti-CD20 antibody protein composition to a subject, about 2.33 mL of a pharmaceutical formulation comprising anti-CD20 antibody proteins at a concentration of about 150 mg / mL can be administered to the subject by subcutaneous injection. For administering about 400 mg of the anti-CD20 antibody protein composition to a subject, about 2.66 mL of a pharmaceutical formulation comprising anti-CD20 antibody proteins at a concentration of about 150 mg / mL can be administered to the subject by subcutaneous injection. For administering about 450 mg of the anti-CD20 antibody protein composition to a subject, about 3 mL of a pharmaceutical formulation comprising anti-CD20 antibody proteins at a concentration of about 150 mg / mL can be administered to the subject by subcutaneous injection. For administering about 500 mg of the anti-CD20 antibody protein composition to a subject, about 3.33 mL of a pharmaceutical formulation comprising anti-CD20 antibody proteins at a concentration of about 150 mg / mL can be administered to the subject by subcutaneous injection.

[0062] The anti-CD20 antibody protein composition can be administered at one or more sites (or locations) in the body of a subject. Sites (or locations) for administration of subcutaneous injections in the body of a subject can include one or more of the following: the outer lateral aspect of the upper arm, the abdomen (e.g., from below the costal margin to the iliac crest and more than two inches from the umbilicus), the anterior upper thighs, the upper back, and the upper ventral gluteal area. In some embodiments, a single subcutaneous dose of an anti-CD20 antibody protein composition described here can be split over multiple administrations. For example, a single subcutaneous dose of an anti-CD20 antibody protein composition that is present in a large volume (e.g., more than 1.5 mL or 2 mL (e.g., 3 mL, 4 mL, 5 mL, 6 mL, 7 mL,Attorney Docket No.50581-0016WO1 8 mL, 9 mL, 10 mL, or more)) can be split over multiple administrations (e.g., can be administered by subcutaneous injection (e.g., of 1-2 mL) at multiple sites, such as, at 2, 3, 4, 5, or more sites) in the body of a subject. In some instances, about 200 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti-CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations). In some instances, about 225 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti-CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations). In some instances, about 250 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti-CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations). In some instances, about 265 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti-CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations). In some instances, about 275 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti- CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations). In some instances, about 300 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti-CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations). In some instances, about 350 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti-CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations). In some instances, about 400 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti-CD20 antibody protein composition is administered at one site in theAttorney Docket No.50581-0016WO1 body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations). In some instances, about 450 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti- CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations). In some instances, about 500 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti-CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations).

[0063] The anti-CD20 antibody protein composition described herein can be administered to a subject subcutaneously (e.g., by subcutaneous injection). The method can include the following: a first dose of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at day 1; a second dose of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at about 2 weeks after the first dose (e.g., at day 15); a third dose of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at about 12 weeks (e.g., about 3 months) after the first dose; and one or more subsequent doses of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at about 12 weeks (e.g., about 3 months) after the prior dose. The method can alternatively include the following: a first dose of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at day 1; a second dose of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at about 2 weeks after the first dose (e.g., at day 15); a third dose of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at about 8 weeks (e.g., about 2 months) after the first dose; and one or more subsequent doses of the anti- CD20 antibody protein composition administered to the subject by subcutaneous injection at about 8 weeks (e.g., about 2 months) after the prior dose. In some embodiments, the method comprises administering to the subject a total of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more doses of the anti-CD20 antibody protein composition. For example, a total of 6 doses of the anti-CD20 antibody protein composition can be administered to the subject by subcutaneous injection. In some instances, the anti-CD20 antibody protein composition is administered to the subject by subcutaneous injection at Day 1, Day 15, Week 12, Week 24, Week 36, Week 48, Week 60,Attorney Docket No.50581-0016WO1 Week 72, Week 84, and Week 96. In some instances, the anti-CD20 antibody protein composition is administered to the subject by subcutaneous injection at Day 1, Day 15, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, and every 12 weeks (or about 3 months) thereafter. In some instances, the subcutaneous anti-CD20 antibody protein composition is administered subcutaneously to the subject at Day 1, Day 15, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56, Week 64, Week 72, Week 80, Week 88, Week 96. In some instances, the subcutaneous anti-CD20 antibody protein composition is administered subcutaneously to the subject at Day 1, Day 15, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56, Week 64, Week 72, Week 80, Week 88, Week 96 and every 8 weeks (or about 2 months) thereafter. The first dose can comprise the population of anti-CD20 antibody proteins in an amount that is bioequivalent to about 150 mg of the population of anti- CD20 antibody proteins administered intravenously. The second dose can comprise the population of anti-CD20 antibody proteins in an amount that is bioequivalent to about 225 mg of the population of anti-CD20 antibody proteins administered intravenously. The third dose can comprise the population of anti-CD20 antibody proteins in an amount that is bioequivalent to about 225 mg of the population of anti-CD20 antibody proteins administered intravenously. The one or more subsequent doses can comprise the population of anti-CD20 antibody proteins in an amount that is bioequivalent to about 225 mg of the population of anti-CD20 antibody proteins administered intravenously. Alternatively, the second dose can comprise the population of anti- CD20 antibody proteins in an amount that is bioequivalent to about 150 mg of the population of anti-CD20 antibody proteins administered intravenously. The third dose can comprise the population of anti-CD20 antibody proteins in an amount that is bioequivalent to about 150 mg of the population of anti-CD20 antibody proteins administered intravenously. The one or more subsequent doses can comprise the population of anti-CD20 antibody proteins in an amount that is bioequivalent to about 150 mg of the population of anti-CD20 antibody proteins administered intravenously. The bioequivalent of the population of anti-CD20 antibody proteins (e.g., bioequivalent of the 150 mg and / or 225 mg of the population of anti-CD20 antibody proteins) administered intravenously can be determined based on the PK / PD and tolerability data, as described in Example 5 of the present disclosure. In some instances, one or more of the first dose, the second dose, the third dose, and the one or more subsequent doses can each comprise about 250 mg to about 500 mg (e.g., about 265 mg to about 450 mg; optionally, about 400 mg)Attorney Docket No.50581-0016WO1 of the population of anti-CD20 antibody proteins. For example, the first dose can comprise about 250 mg to about 500 mg (e.g., about 265 mg to about 450 mg; optionally, about 400 mg) of the population of anti-CD20 antibody proteins; the second dose can comprise about 250 mg to about 500 mg (e.g., about 265 mg to about 450 mg; optionally, about 400 mg) of the population of anti-CD20 antibody proteins; the third dose can comprise about 250 mg to about 500 mg (e.g., about 265 mg to about 450 mg; optionally, about 400 mg) of the population of anti-CD20 antibody proteins; and / or the one or more subsequent doses can each comprise about 250 mg to about 500 mg (e.g., about 265 mg to about 450 mg; optionally, about 400 mg) of the population of anti-CD20 antibody proteins. Preferably, the first dose can comprise about 400 mg of the population of anti-CD20 antibody proteins; the second dose can comprise about 400 mg of the population of anti-CD20 antibody proteins; the third dose can comprise about 400 mg of the population of anti-CD20 antibody proteins; and / or the one or more subsequent doses can each comprise about 400 mg of the population of anti-CD20 antibody proteins. Administration by Subcutaneous and Intravenous Combination

[0064] The anti-CD20 antibody protein composition described herein can also be administered to a subject by a combination of subcutaneous injection and intravenous infusion. Administration of the anti-CD20 antibody protein composition to a subject by a combination of subcutaneous injection and intravenous infusion can include the following: a first dose of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at day 1; a second dose of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 2 weeks after the first dose (e.g., at day 15); a third dose of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion infusion at about 6 months (e.g., about 24 weeks) after the first dose; and one or more subsequent doses of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 6 months (e.g., about 24 weeks) after the prior dose. In some embodiments, the method comprises administering to the subject a total of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more doses of the anti-CD20 antibody protein composition. For example, a total of 6 doses of the anti-CD20 antibody protein composition can be administered to the subject. In some instances, the anti- CD20 antibody protein composition is administered to the subject at Day 1, Day 15, Week 24, Week 48, Week 72, Week 96, and every 24 week (or 6 months) thereafter. In someAttorney Docket No.50581-0016WO1 embodiments, the method comprises a treatment period of about 24-96 weeks (e.g., about 24-48 weeks, about 48-72 weeks, or about 72-96 weeks (e.g., about 24 weeks, about 48 weeks, about 72 weeks, or about 96 weeks)), about 1-10 years (e.g., about 1-3 years, about 2-4 years, about 3- 5 years, about 4-6 years, about 5-7 years, about 6-8 years, about 7-9 years, or about 8-10 years (e.g., about 1 year, about 2 years, about 3 years, about 4 years, about 5 years, about 6 years, about 7 years, about 8 years, about 9 years, or about 10 years)), or more. In some embodiments, the method comprises a treatment period of at least 24 weeks, at least 48 weeks, at least 72 weeks, or at least 96 weeks. For example, the method can comprise a treatment period of at least 48 weeks or 96 weeks. In some embodiments, the method comprises a treatment period of at least 1 year, at least 2 years, at least 3 years, at least 4 years, at least 5 years, at least 6 years, at least 7 years, at least 8 years, at least 9 years, or at least 10 years.

[0065] The first dose can comprise about 25 mg to about 400 mg (e.g., about 25 mg to about 50 mg, about 50 mg to about 100 mg, about 100 mg to about 150 mg, about 150 mg to about 200 mg, about 200 mg to about 250 mg, about 250 mg to about 300 mg, about 300 mg to about 350 mg, about 350 mg to about 400 mg, about 50 mg to about 200 mg, about 50 mg to about 300 mg, about 50 mg to about 400 mg, about 100 mg to about 200 mg, about 100 mg to about 300 mg, about 100 mg to about 400 mg, about 150 mg to about 200 mg, about 150 mg to about 300 mg, about 150 mg to about 400 mg, about 200 mg to about 300 mg, about 200 mg to about 400 mg (such as, about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, or about 400 mg)) of the anti-CD20 antibody protein composition that is administered to a subject by subcutaneous injection. In some instances, about 50 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection as a first dose. In some instances, about 100 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. In some instances, about 150 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. In some instances, about 225 mg of the anti-CD20 antibody protein composition can be administered to a subject by subcutaneous injection. In some instances, about 300 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. In some instances, about 400 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection. The first dose can beAttorney Docket No.50581-0016WO1 administered subcutaneously to the subject by a healthcare professional (e.g., a physician, a nurse practitioner, a nurse, a physician assistant, a nursing assistant, and / or a medical assistant); and / or the first dose can be self-administered by the subject as a subcutaneous injection.

[0066] In some embodiments, a pharmaceutical formulation comprising anti-CD20 antibody proteins at a concentration of about 150 mg / ml is administered as a first dose to a subject by subcutaneous injection. For example, for administering a first dose comprising about 50 mg of the anti-CD20 antibody protein composition to a subject, about 0.33 ml of a pharmaceutical formulation comprising the anti-CD20 antibody proteins at a concentration of about 150 mg / ml can be administered to the subject by subcutaneous injection. For administering a first dose comprising about 100 mg of the anti-CD20 antibody protein composition to a subject, about 0.66 ml of a pharmaceutical formulation comprising the anti-CD20 antibody proteins at a concentration of about 150 mg / ml can be administered to the subject by subcutaneous injection. For administering a first dose comprising about 150 mg of the anti-CD20 antibody protein composition to a subject, about 1.0 ml of a pharmaceutical formulation comprising the anti- CD20 antibody proteins at a concentration of about 150 mg / ml can be administered to the subject by subcutaneous injection. For administering a first dose comprising about 225 mg of the anti- CD20 antibody protein composition to a subject, about 1.5 ml of a pharmaceutical formulation comprising the anti-CD20 antibody proteins at a concentration of about 150 mg / ml can be administered to the subject by subcutaneous injection. For administering a first dose comprising about 300 mg of the anti-CD20 antibody protein composition to a subject, about 2.0 ml of a pharmaceutical formulation comprising anti-CD20 antibody proteins at a concentration of about 150 mg / ml can be administered to the subject by subcutaneous injection. For administering a first dose comprising about 400 mg of the anti-CD20 antibody protein composition to a subject, about 2.66 ml of a pharmaceutical formulation comprising anti-CD20 antibody proteins at a concentration of about 150 mg / ml can be administered to the subject by subcutaneous injection.

[0067] A first dose comprising the anti-CD20 antibody protein composition can be administered subcutaneously at one or more sites (or locations) in the body of a subject. Sites (or locations) for administration of subcutaneous injections in the body of a subject can include one or more of the following: the outer lateral aspect of the upper arm, the abdomen (e.g., from below the costal margin to the iliac crest and more than two inches from the umbilicus), the anterior upper thighs, the upper back, and the upper ventral gluteal area. In some embodiments,Attorney Docket No.50581-0016WO1 a single first dose of an anti-CD20 antibody protein composition described here can be split over multiple subcutaneous administrations. For example, a single first dose of an anti-CD20 antibody protein composition that is present in a large volume (e.g., more than 2 ml (e.g., 3 ml, 4 ml, 5 ml, 6 ml, 7 ml, 8 ml, 9 ml, 10 ml, or more)) can be split over multiple subcutaneous administrations (e.g., can be administered by subcutaneous injection at multiple sites, such as, at 2, 3, 4, 5, or more sites) in the body of a subject. In some instances, a first dose comprising about 50 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti-CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations). In some instances, a first dose comprising about 100 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti-CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations). In some instances, a first dose comprising about 150 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti-CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations). In some instances, a first dose comprising about 225 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti-CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations). In some instances, a first dose comprising about 300 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti-CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations). In some instances, a first dose comprising about 400 mg of the anti-CD20 antibody protein composition is administered to a subject by subcutaneous injection, wherein the anti-CD20 antibody protein composition is administered at one site in the body of the subject or at multiple sites in the body of the subject (e.g., a subcutaneous dose is split over multiple administrations).Attorney Docket No.50581-0016WO1

[0068] In some embodiments, the second dose comprises about 400 mg to about 500 mg (e.g., about 450 mg) of the anti-CD20 antibody protein composition. In some embodiments, the third dose comprises about 400 mg to about 500 mg (e.g., about 450 mg) of the anti-CD20 antibody protein composition. In some embodiments, the one or more subsequent doses comprise about 400 mg to about 500 mg (e.g., about 450 mg) of the anti-CD20 antibody protein composition. For example, the anti-CD20 antibody protein composition described here can be administered to the subject by a dosing regimen, comprising: a) a first dose comprising about 25 mg to about 300 mg (e.g., about 50 mg, about 100 mg, about 150 mg, about 225 mg, or about 300 mg) of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at day 1; a second dose comprising about 400 mg to about 500 mg (e.g., about 450 mg) of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 2 weeks after the first dose (e.g., at day 15); a third dose comprising about 400 mg to about 500 mg (e.g., about 450 mg) of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion infusion at about 6 months (e.g., about 24 weeks) after the first dose; and one or more subsequent doses comprising about 400 mg to about 500 mg (e.g., about 450 mg) of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 6 months (e.g., about 24 weeks) after the prior dose. The first dose can be a priming dose or loading dose. A loading dose can be used for depleting B-cells in a subject. For example, a first dose, comprising about 25 mg to about 400 mg (e.g., about 50 mg, about 100 mg, about 150 mg, about 225 mg, about 300 mg, or about 400 mg) of the anti-CD20 antibody protein composition, can be used as a priming dose or loading dose for depleting B-cells in a subject prior to a first full dose that comprises about 400 mg to about 500 mg (e.g., about 450 mg) of the anti-CD20 antibody protein composition. Each of the second dose, third dose, and one or more subsequent doses can be a maintenance dose. In some embodiments, the first dose is given by subcutaneous injection over one administration (e.g., administered at one site in the body of the subject). In some embodiments, the first dose is split over multiple administrations by subcutaneous injection (e.g., administered by subcutaneous injection at multiple sites in the body of the subject; or administered multiple times by subcutaneous injections at the same site in the body of the subject). In some embodiments, the first dose is administered to the subject (e.g., by subcutaneous injection) by a healthcare professional. In some embodiments, the first dose isAttorney Docket No.50581-0016WO1 self-administered (e.g., by subcutaneous injection) by the subject. In some embodiments, each of the second dose, the third dose, and the one or more subsequent doses is administered to the subject by intravenous infusion over 1 hour.

[0069] In some embodiments, the anti-CD20 antibody protein composition described here is administered to the subject by a combination of subcutaneous injection and intravenous infusion, e.g., by a dosing regimen comprising: a) a first dose comprising about 50 mg of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at day 1; a second dose comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 2 weeks after the first dose (e.g., at day 15); a third dose comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion infusion at about 6 months (e.g., about 24 weeks) after the first dose; and one or more subsequent doses comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 6 months (e.g., about 24 weeks) after the prior dose. In some embodiments, the first dose is given by subcutaneous injection over one administration (e.g., administered at one site in the body of the subject). In some embodiments, the first dose is split over multiple administrations by subcutaneous injection (e.g., administered by subcutaneous injection at multiple sites in the body of the subject; or administered multiple times by subcutaneous injections at the same site in the body of the subject). In some embodiments, the first dose is administered to the subject (e.g., by subcutaneous injection) by a healthcare professional. In some embodiments, the first dose is self-administered (e.g., by subcutaneous injection) by the subject. In some embodiments, the second dose is administered by intravenous infusion over 1 hour; the third dose is administered by intravenous infusion over 1 hour; and the one or more subsequent doses is administered by intravenous infusion over 1 hour. In some embodiments, the method comprises administering to the subject a total of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more doses of the anti-CD20 antibody protein composition. For example, a total of 6 or more doses of the anti-CD20 antibody protein composition can be administered to the subject.

[0070] In some embodiments, the anti-CD20 antibody protein composition described here is administered to the subject by a combination of subcutaneous injection and intravenous infusion, e.g., by a dosing regimen comprising: a) a first dose comprising about 100 mg of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at day 1; aAttorney Docket No.50581-0016WO1 second dose comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 2 weeks after the first dose (e.g., at day 15); a third dose comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion infusion at about 6 months (e.g., about 24 weeks) after the first dose; and one or more subsequent doses comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 6 months (e.g., about 24 weeks) after the prior dose. In some embodiments, the first dose is given by subcutaneous injection over one administration (e.g., administered at one site in the body of the subject). In some embodiments, the first dose is split over multiple administrations by subcutaneous injection (e.g., administered by subcutaneous injection at multiple sites in the body of the subject; or administered multiple times by subcutaneous injections at the same site in the body of the subject). In some embodiments, the first dose is administered to the subject (e.g., by subcutaneous injection) by a healthcare professional. In some embodiments, the first dose is self-administered (e.g., by subcutaneous injection) by the subject. In some embodiments, the second dose is administered by intravenous infusion over 1 hour; the third dose is administered by intravenous infusion over 1 hour; and the one or more subsequent doses is administered by intravenous infusion over 1 hour. In some embodiments, the method comprises administering to the subject a total of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more doses of the anti-CD20 antibody protein composition. For example, a total of 6 or more doses of the anti-CD20 antibody protein composition can be administered to the subject.

[0071] In some embodiments, the anti-CD20 antibody protein composition described here is administered to the subject by a combination of subcutaneous injection and intravenous infusion, e.g., by a dosing regimen comprising: a) a first dose comprising about 150 mg of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at day 1; a second dose comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 2 weeks after the first dose (e.g., at day 15); a third dose comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion infusion at about 6 months (e.g., about 24 weeks) after the first dose; and one or more subsequent doses comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 6 months (e.g., about 24 weeks) after the prior dose. In some embodiments, the first doseAttorney Docket No.50581-0016WO1 is given by subcutaneous injection over one administration (e.g., administered at one site in the body of the subject). In some embodiments, the first dose is split over multiple administrations by subcutaneous injection (e.g., administered by subcutaneous injection at multiple sites in the body of the subject; or administered multiple times by subcutaneous injections at the same site in the body of the subject). In some embodiments, the first dose is administered to the subject (e.g., by subcutaneous injection) by a healthcare professional. In some embodiments, the first dose is self-administered (e.g., by subcutaneous injection) by the subject. In some embodiments, the second dose is administered by intravenous infusion over 1 hour; the third dose is administered by intravenous infusion over 1 hour; and the one or more subsequent doses is administered by intravenous infusion over 1 hour. In some embodiments, the method comprises administering to the subject a total of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more doses of the anti-CD20 antibody protein composition. For example, a total of 6 or more doses of the anti-CD20 antibody protein composition can be administered to the subject.

[0072] In some embodiments, the anti-CD20 antibody protein composition described here is administered to the subject by a combination of subcutaneous injection and intravenous infusion, e.g., by a dosing regimen comprising: a) a first dose comprising about 225 mg of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at day 1; a second dose comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 2 weeks after the first dose (e.g., at day 15); a third dose comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion infusion at about 6 months (e.g., about 24 weeks) after the first dose; and one or more subsequent doses comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 6 months (e.g., about 24 weeks) after the prior dose. In some embodiments, the first dose is given by subcutaneous injection over one administration (e.g., administered at one site in the body of the subject). In some embodiments, the first dose is split over multiple administrations by subcutaneous injection (e.g., administered by subcutaneous injection at multiple sites in the body of the subject; or administered multiple times by subcutaneous injections at the same site in the body of the subject). In some embodiments, the first dose is administered to the subject (e.g., by subcutaneous injection) by a healthcare professional. In some embodiments, the first dose is self-administered (e.g., by subcutaneous injection) by the subject. In some embodiments, theAttorney Docket No.50581-0016WO1 second dose is administered by intravenous infusion over 1 hour; the third dose is administered by intravenous infusion over 1 hour; and the one or more subsequent doses is administered by intravenous infusion over 1 hour. In some embodiments, the method comprises administering to the subject a total of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more doses of the anti-CD20 antibody protein composition. For example, a total of 6 or more doses of the anti-CD20 antibody protein composition can be administered to the subject.

[0073] In some embodiments, the anti-CD20 antibody protein composition described here is administered to the subject by a combination of subcutaneous injection and intravenous infusion, e.g., by a dosing regimen comprising: a) a first dose comprising about 300 mg of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at day 1; a second dose comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 2 weeks after the first dose (e.g., at day 15); a third dose comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion infusion at about 6 months (e.g., about 24 weeks) after the first dose; and one or more subsequent doses comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 6 months (e.g., about 24 weeks) after the prior dose. In some embodiments, the first dose is given by subcutaneous injection over one administration (e.g., administered at one site in the body of the subject). In some embodiments, the first dose is split over multiple administrations by subcutaneous injection (e.g., administered by subcutaneous injection at multiple sites in the body of the subject; or administered multiple times by subcutaneous injections at the same site in the body of the subject). In some embodiments, the first dose is administered to the subject (e.g., by subcutaneous injection) by a healthcare professional. In some embodiments, the first dose is self-administered (e.g., by subcutaneous injection) by the subject. In some embodiments, the second dose is administered by intravenous infusion over 1 hour; the third dose is administered by intravenous infusion over 1 hour; and the one or more subsequent doses is administered by intravenous infusion over 1 hour. In some embodiments, the method comprises administering to the subject a total of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more doses of the anti-CD20 antibody protein composition. For example, a total of 6 or more doses of the anti-CD20 antibody protein composition can be administered to the subject.Attorney Docket No.50581-0016WO1

[0074] In some embodiments, the anti-CD20 antibody protein composition described here is administered to the subject by a combination of subcutaneous injection and intravenous infusion, e.g., by a dosing regimen comprising: a) a first dose comprising about 400 mg of the anti-CD20 antibody protein composition administered to the subject by subcutaneous injection at day 1; a second dose comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 2 weeks after the first dose (e.g., at day 15); a third dose comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion infusion at about 6 months (e.g., about 24 weeks) after the first dose; and one or more subsequent doses comprising about 450 mg of the anti-CD20 antibody protein composition administered to the subject by intravenous infusion at about 6 months (e.g., about 24 weeks) after the prior dose. In some embodiments, the first dose is given by subcutaneous injection over one administration (e.g., administered at one site in the body of the subject). In some embodiments, the first dose is split over multiple administrations by subcutaneous injection (e.g., administered by subcutaneous injection at multiple sites in the body of the subject; or administered multiple times by subcutaneous injections at the same site in the body of the subject). In some embodiments, the first dose is administered to the subject (e.g., by subcutaneous injection) by a healthcare professional. In some embodiments, the first dose is self-administered (e.g., by subcutaneous injection) by the subject. In some embodiments, the second dose is administered by intravenous infusion over 1 hour; the third dose is administered by intravenous infusion over 1 hour; and the one or more subsequent doses is administered by intravenous infusion over 1 hour. In some embodiments, the method comprises administering to the subject a total of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more doses of the anti-CD20 antibody protein composition. For example, a total of 6 or more doses of the anti-CD20 antibody protein composition can be administered to the subject. Diseases Inflammatory and Autoimmune Diseases

[0075] In some embodiments, provided herein is a method of treating an autoimmune disease in a subject in need thereof, by administering to the subject an effective amount of an anti-CD20 antibody protein composition of the present disclosure.Attorney Docket No.50581-0016WO1

[0076] Autoimmune diseases cover diseases that occur when the body's immune system attacks its own normal tissues, organs or other in vivo components due to immune system abnormalities whose cause cannot be found. These autoimmune diseases are systemic diseases that can occur in almost all parts of the body, including the nervous system, the gastrointestinal system, the endocrine system, the skin, the skeletal system, and the vascular tissue. It is known that autoimmune diseases affect about 5-8% of the world population, but the reported prevalence of autoimmune diseases is lower than the actual level due to limitations in the understanding of autoimmune diseases and a method for diagnosing these diseases.

[0077] In some embodiments, the autoimmune disease is multiple sclerosis (MS). In some embodiments, the MS is a relapsing form of MS (RMS). For example, provided herein is a method of treating an RMS in a subject in need thereof, by administering to the subject an effective amount of an anti-CD20 antibody protein composition of the present disclosure. The MS can be a clinically isolated syndrome (“CIS”), relapsing-remitting (“RRMS”), active secondary progressive disease (“SPMS”), or primary progressive MS (PPMS). In some embodiments, the MS is a CIS. In some embodiments, the MS is RRMS. In some embodiments, the MS is SPMS. In some embodiments, the MS is PPMS. In some embodiments, the subject is diagnosed with MS in accordance with the 2017 Revised McDonald Criteria. In some embodiments, the subject has an Expanded Disability Status Scale (EDSS) score of from 0 to 5.5 prior to treatment with the anti-CD20 antibody protein composition described herein.

[0078] In some embodiments, the autoimmune disease is lupus, or Systemic lupus erythematosus (SLE). In some embodiments, the lupus is systemic lupus erythematosus (SLE). In some embodiments, the lupus is cutaneous lupus erythematosus or lupus of the skin (e.g., acute cutaneous lupus, chronic cutaneous lupus erythematosus or discoid lupus erythematosus (DLE), and / or subacute cutaneous lupus erythematosus). In some embodiments, the lupus is drug-induced lupus erythematosus (e.g., lupus induced by the use of one or more of Hydralazine (e.g., used to treat high blood pressure or hypertension), Procainamide (e.g., used to treat irregular heart rhythms), Isoniazid (e.g., used to treat tuberculosis), Minocycline (e.g., used to treat acne), and anti-TNF (e.g., used to treat rheumatoid arthritis, psoriatic arthritis and spondyloarthropathy)). In some some embodiments, the lupus is neonatal lupus.

[0079] In some embodiments, the autoimmune disease is rheumatoid arthritis (RA). For example, provided herein is a method of treating RA in a subject in need thereof, byAttorney Docket No.50581-0016WO1 administering to the subject an effective amount of an anti-CD20 antibody protein composition of the present disclosure. In some embodiments, the RA is rheumatoid factor positive RA or seropositive RA. In some embodiments, the RA is rheumatoid factor negative RA or seronegative RA.

[0080] In some embodiments, the autoimmune disease is myasthenia gravis (MG). For example, provided herein is a method of treating MG in a subject in need thereof, by administering to the subject an effective amount of an anti-CD20 antibody protein composition of the present disclosure. In some embodiments, the MG is oculobulbar MG. In some embodiments, the MG is bulbar MG. In some embodiments, the MG is generalized MG.

[0081] In some embodiments, the autoimmune disease is chronic idiopathic demyelinating polyneuropathy (CIDP). For example, provided herein is a method of treating CIDP in a subject in need thereof, by administering to the subject an effective amount of an anti-CD20 antibody protein composition of the present disclosure.

[0082] In some embodiments, provided herein is a method of treating and / or preventing one or more of the following autoimmune conditions (or autoimmune diseases) in a subject in need thereof, by administering to the subject an effective amount of an anti-CD20 antibody protein composition of the present disclosure: Chronic inflammatory demyelinating polyneuropathy (CIDP); Myositis; Lupus Nephritis; other forms of MS, e.g., PPMS or SPMS; Myasthenia Gravis (MG); Antiphospholipid Syndrome; Thrombotic Thrombocytopenic Purpura (TTP); Ulcerative Colitis; Minimal Change Nephrotic Syndrome (MCNS); Aplastic Anemia; Autoimmune Glomerulopathies; Rheumatoid Arthritis (RA); Interstitial Lung Disease; Subepidermal Autoimmune Blistering Disease; Pulmonary Infectious Diseases; Acquired Hemophilia; Refractory Mixed Cryoglobulinemia; Primary Immune Thrombocytopenia; Graft Versus Host Disease (GVHD); Autoimmune Blistering Disease; Anti-Myelin Associated Glycoprotein (MAG) Polyneuropathy; Granulomatosis with Pollyangiitis (GPA); Neuromyelitis Optica; Systemic Lupus Erythematosus; Pemphigus; Post-Transplant Lymphoproliferative Disorders; Autoimmune Hemolytic Anemia; Cerebral Vasculitis; Microscopic Polyangiitis (MPA); and Idiopathic Nephritic Syndrome.

[0083] In some embodiments, provided herein is a method of treating and / or preventing one or more of the following autoimmune conditions (or autoimmune diseases) in a subject in need thereof, by administering to the subject an effective amount of an anti-CD20 antibody proteinAttorney Docket No.50581-0016WO1 composition of the present disclosure: multiple sclerosis (MS), myasthenia gravis (MG), psoriasis, rheumatoid arthritis (RA), vasculitis, inflammatory bowel disease, dermatitis, osteoarthritis, inflammatory muscle disease, allergic rhinitis, vaginitis, interstitial cystitis, scleroderma, osteoporosis, eczema, allogenic or xenogenic transplantation (organ, bone marrow, stem cells and other cells and tissues), graft rejection, graft-versus-host disease, lupus erythematosus, inflammatory disease, type 1 diabetes, pulmonary fibrosis, dermatomyositis, Sjogren's syndrome, thyroiditis (e.g., Hasimoto's and autoimmune thyroiditis), autoimmune hemolytic anemia, cystic fibrosis, chronic relapsing hepatitis, primary biliary cirrhosis, allergic conjunctivitis, atopic dermatitis, chronic obstructive pulmonary disease, glomerulonephritis, neuroinflammatory diseases, and uveitis. Subject

[0084] In some embodiments, the subject is a human. In some embodiments, the human subject is an adult (i.e., 18 years or older).

[0085] In some embodiments, the subject is diagnosed with one or more autoimmune diseases (e.g., one or more of MS, lupus, RA, and MG) prior to treatment with the present methods. In some embodiments, the subject shows one or more symptoms of an autoimmune diseases (e.g., one or more of MS, lupus, RA, and MG) prior to treatment with the present methods. In some embodiments, the subject has experienced at least one relapse in the previous year prior to treatment or two relapses in the previous two years prior to treatment. In some embodiments, the subject has or had the presence of a T1 gadolinium (Gd)-enhancing lesion in the previous year prior to treatment with the anti-CD20 antibody protein composition as described herein. In some embodiments, the subject has an Expanded Disability Status Scale (EDSS) score of from 0 to 5.5 prior to treatment with the anti-CD20 antibody protein composition as described herein. In some embodiments, the subject is neurologically stable for > 30 days prior to Day 1 (i.e., prior to start of the treatment). In some embodiments, the subject has IgG > 4.0 g / L at screening (e.g., prior to start of treatment).

[0086] In certain embodiments of the method, the subject has not been treated with a non- steroid therapy for MS in the previous five years prior to treatment with the anti-CD20 antibody protein composition as described herein. In some embodiments, the subject is naïve to treatment for MS. In certain embodiments, the subject is negative for hepatitis B virus (HBV). In someAttorney Docket No.50581-0016WO1 embodiments, the subject is negative for hepatitis B virus surface antigen (HBsAg). In some embodiments, the subject is negative for anti-hepatitis B virus core antibodies. In certain embodiments, the subject has not been immunized with a vaccine for at least 2 weeks or at least 4 weeks prior to treatment with the anti-CD20 antibody protein composition as described herein.

[0087] In certain embodiments of the methods described herien, the subject is pre-medicated with an amount of a corticosteroid about 30 to about 60 minutes prior to administration of the anti-CD20 antibody protein composition as described herein. In some embodiments, the corticosteroid is methylprednisone or a corticosteroid bioequivalent thereto. In some embodiments, the amount of a corticosteroid is 100 mg methylprednisone. In some embodiments, the corticosteroid is dexamethasone or a corticosteroid bioequivalent thereto. In some embodiments, the amount of a corticosteroid is of from 10 to 20 mg dexamethasone. In some embodiments, the corticosteroid is administered intravenously. In some embodiments, the corticosteroid is administered orally. In certain embodiments, the subject is pre-medicated with an amount of an antipyretic about 30 to about 60 minutes prior to administration of the anti- CD20 antibody protein composition as described herein. In some embodiments, the antipyretic is acetaminophen or an antipyretic bioequivalent thereto. In some embodiments, the antipyretic is administered intravenously. In some embodiments, the antipyretic is administered orally. In some embodiments, the subject is pre-medicated with an amout of an antihistamine about 30 to about 60 minutes prior to administration of the anti-CD20 antibody protein composition as described herein. In some embodiments, the antihistamine is diphenhydramine HCl or an antihistamine bioequivalent thereof. In some embodiments, the amount of an antihistamine is from about 25 to 50 mg diphenhydramine HCl. In some embodiments, the antihistamine is a non-drowsy antihistamine. In some embodiments, the non-drowsy antihistamine is cetirizine. In some embodiments, the amount of non-drowsy antihistamine is about 10 mg cetirizine. In some embodiments, the non-drowsy antihistamine is loratadine. In some embodiments, the amount of non-drowsy antihistamine is about 10 mg loratadine. In some embodiments, the antihistamine is administered intravenously. In some embodiments, the antihistamine is administered orally. In some embodiments, the subject is pre-medicated with an amount of a corticosteroid (as described above) and an amount of an antihistamine (as described above) about 30 to about 60 minutes prior to administration of the anti-CD20 antibody protein composition as described herein.Attorney Docket No.50581-0016WO1

[0088] In some embodiments, the method alleviates or delays progression of one or more symptoms of an autoimmune disease in the subject. For example, the method can alleviate or delay progression of one or more symptoms of MS, lupus, and / or RA in the subject. In certain embodiments, the method reduces the annualized relapse rate (ARR) in the subject following administration of the anti-CD20 antibody protein composition as described herein. In some embodiments, ARR is the total number of relapse / s for a subject divided by the sum of treatment duration. In some embodiments, ARR is number of Independent Relapse Adjudication Panel (IRAP)-confirmed relapses for a subject per year. In some embodiments, reduction of ARR is assessed at about 96 weeks after the first infusion. In certain embodiments, the method reduces the total number of T1 gadolinium (Gd)-enhancing lesions in the subject following administration of the anti-CD20 antibody protein composition as described herein. In some embodiments, reduction of Gd-enhancing T1 lesions is assessed by MRI scan. In some embodiments, reduction of Gd-enhancing T1 lesions is assessed at about 96 weeks after the first infusion. In certain embodiments, the method reduces the number of new or enlarging T2 hyperintense lesions in the subject following administration of the anti-CD20 antibody protein composition as described herein. In some embodiments, reduction of the number of new or enlarging T2 hyperintense lesions is assessed by MRI scan. In some embodiments, reduction of the number of new or enlarging T2 hyperintense lesions is assessed at about 96 weeks after the first infusion. In certain embodiments, the method achieves confirmed disability progression in the subject following administration of the anti-CD20 antibody protein composition as described herein. In some embodiments, confirmation of disability progression comprises an increase of greater than or equal to 1.0 point from a baseline EDSS score of the subject attributable to MS, wherein said baseline EDSS score is 5.5 or less. In some embodiments, confirmation of disability progression comprises an increase of greater than or equal to 0.5 point from a baseline EDSS score of the subject attributable to MS, wherein said baseline EDSS score is greater than 5.5. 7.7 Pharmacokinetic Properties

[0089] In certain embodiments, the administration of the anti-CD20 antibody produces an area under the curve (AUC) of between about 2,160 g / mL and about 3,840 g / mL. In certain embodiments, the AUC is about 3,000 g / mL. In certain embodiments, the AUC is the steady state AUC.Attorney Docket No.50581-0016WO1

[0090] In certain embodiments, the administration of the anti-CD20 antibody produces an Cmax of between about 118,011 ng / mL and about 159,989 ng / mL. In certain embodiments, the Cmax is about 139,000 ng / mL. In certain embodiments, the Cmax is the steady state Cmax.

[0091] In certain embodiments, the administration of the anti-CD20 antibody produces a Cmin of about 0 ng / mL and about 375 ng / mL. In certain embodiments, the Cmin is about 139 ng / mL. In certain embodiments, the Cminis the steady state Cmin.

[0092] In certain embodiments, the administration of the anti-CD20 antibody produces a Cavgof between about 6,437 ng / mL and about 11,443 ng / mL. In certain embodiments, the Cavgis about 8,940 ng / mL. In certain embodiments, the Cavgis the steady state Cavg.

[0093] In certain embodiments, the anti-CD20 antibody is administered entirely subcutaneously. In certain embodiments, the anti-CD20 antibody is administered through a combination of subcutaneous and intravenous administrations. 7.8 Methods of Making

[0094] Also provided herein are methods of making the populations of anti-CD20 antibody proteins with specified ranges of post-translational modifications. A detailed description of such methods is provided in WO 2023 / 235762 and WO 2023 / 235764, the entire contents of which are incorporated herein by reference. Also, Example 3 provides exemplary methods of making the populations of anti-CD20 antibody proteins provided herein.

[0095] In certain embodiments, the methods of making the populations of anti-CD20 antibody proteins with specified ranges of post-translational modifications as described above comprises: i) culturing the rat hybridoma cells at a first culture pH of about 7.0 to about 7.55 for 0 to 3 days, ii) culturing the rat hybridoma cells at a second culture pH of about 6.5 to about 6.99 on day 3, iii) maintaining the culture pH at the second culture pH of about 6.5 to about 6.99 from culture day 3 until day 14 of the cell culture, and iv) controlling culture pCO2levels to less than about 200 mmHg throughout the culture period. In some embodiments, the second culture pH is about 6.60 to about 6.96 (e.g., the second culture pH is 6.8).

[0096] In some embodiments, the second culture pH results in higher integrated viable cell density (IVCD) and higher titer at harvest.

[0097] In some embodiments, the second culture pH results in lower percent fucosylation.Attorney Docket No.50581-0016WO1

[0098] In some embodiments, the rat hybridoma cells expressing the recombinant protein are cultured in a basal media that is chemically defined and animal-derived component free (ADCF) culture medium.

[0099] In some embodiments, the basal medium is supplemented with a feed medium.

[0100] The method can further comprise an initial temperature set point of about 37°C, wherein said initial temperature set point is set on culture day 0 to culture day 1.

[0101] In some embodiments, the method further comprises a second temperature set point of about 35°C, wherein said second temperature set point is set at the end of culture day 1 to culture day 3.

[0102] In some embodiments, the method further comprises comprising a third temperature set point of about 32°C to about 33°C, wherein said third temperature set point is set on culture day 3 and is maintained though harvest. The term “harvest” refers to the point of time in the mammalian cell culture process when cells containing the recombinant protein are separated and removed from the cell culture media and subject to additional processing, such as, e.g., centrifugation, filtration, or purification.

[0103] In some embodiments, harvest of the cells will occur on process day 12, 13, or 14 of the cell culture, or when cell viability drops below 20%, whichever comes first.

[0104] In some embodiments, the method further comprises harvesting the recombinant protein produced by the rat hybridoma cell.

[0105] In some embodiments, the method further comprises purifying the recombinant protein by affinity chromatography and / or ion exchange chromatography. In some embodiments, the affinity chromatography comprises protein A purification.

[0106] In some embodiments, the methods result in an increased yield of recombinant protein. For example, the recombinant protein is increased by at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 100%, at least about 110%, at least about 120%, at least about 130%, at least about 140%, or at least about 150%, relative to a recombinant protein produced by a culturing process that does not employ the culture conditions as recited above.Attorney Docket No.50581-0016WO1 Single Use Vial

[0107] The antibody proteins of the population can be present in a single dosage form. For example, the present disclosure provides single use vials comprising anti-CD20 antibody proteins (and / or a population thereof) in a single dosage form. In some embodiments, the single use vials comprise a pharmaceutical formulation that comprises anti-CD20 antibody proteins (and / or a population thereof) in a single dosage form. In some embodiments, the present disclosure provides single use vials that comprise pharmaceutical formulations comprising 25 mg / mL to 180 mg / mL (e.g., 25 mg / mL to 170 mg / mL; 25 mg / mL to 160 mg / mL; 25 mg / mL to 150 mg / mL; 50 mg / mL to 150 mg / mL; 75 mg / mL to 150 mg / mL; 100 mg / mL to 150 mg / mL; or 125 mg / mL to 150 mg / mL (e.g., about 25 mg / mL; about 50 mg / mL; about 100 mg / mL; about 125 mg / mL; or (preferably) about 150 mg / mL)) anti-CD20 antibody proteins (and / or a population thereof) in a single dosage form.

[0108] In some embodiments, the present disclosure provides single use vials that comprise 25 mg / mL, 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 55 mg / mL, 60 mg / mL, 65 mg / mL, 70 mg / mL, 75 mg / mL, 100 mg / mL, 125 mg / mL, 150 mg / mL, 160 mg / mL, 170 mg / mL, or 180 mg / mL anti-CD20 antibody proteins (or a population thereof) in a pharmaceutical formulation, optionally in a volume of at least about 0.5 mL to about 2 mL or 2.5 mL, optionally at least 0.5 mL up to 1 mL, 1.5 mL, 2 mL, 3 mL, 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, or 10 mL in a single use vial (e.g., a single use vial with a capacity of up to 1 mL, 2 mL, 3 mL, 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, or 10 mL). In some embodiments, the present disclosure provides 25 mg / mL anti-CD20 antibody proteins (or a population thereof) in a pharmaceutical formulation in a volume of 1 mL, 2 mL, 3 mL, 4 mL, 5 mL, or 6 mL in a single use vial. For example, a single use vial of the present disclosure can comprise a pharmaceutical formulation comprising about 25 mg / mL of the anti-CD20 antibody proteins (or a population thereof) in a total volume of 6 mL. In some embodiments, the present disclosure provides 150 mg / mL anti-CD20 antibody proteins (or a population thereof) in a pharmaceutical formulation in a volume of 0.5 mL, 1 mL, 2 mL, 3 mL, 4 mL, or 5 mL in a single use vial (e.g., a single use vial with a capacity of 5 mL or 10 mL). For example, a single use vial of the present disclosure can comprise a pharmaceutical formulation comprising about 150 mg / mL of the anti-CD20 antibody proteins (or a population thereof) for delivery to a subject in a total volume of 1 mL or 2 mL.Attorney Docket No.50581-0016WO1 Pre-Filled Syringe

[0109] The antibody proteins of the population can be present in a single dosage form. For example, the present disclosure provides pre-filled syringes comprising anti-CD20 antibody proteins (and / or a population thereof) in a single dosage form. In some embodiments, the pre- filled syringes comprise a pharmaceutical formulation that comprises anti-CD20 antibody proteins (and / or a population thereof) in a single dosage form. In some embodiments, the present disclosure provides pre-filled syringes that comprise pharmaceutical formulations comprising 25 mg / mL to 180 mg / mL (e.g., 25 mg / mL to 170 mg / mL; 25 mg / mL to 160 mg / mL; 25 mg / mL to 150 mg / mL; 50 mg / mL to 150 mg / mL; 75 mg / mL to 150 mg / mL; 100 mg / mL to 150 mg / mL; or 125 mg / mL to 150 mg / mL (e.g., about 25 mg / mL; about 50 mg / mL; about 100 mg / mL; about 125 mg / mL; or (preferably) about 150 mg / mL)) anti-CD20 antibody proteins (and / or a population thereof) in a single dosage form. In some embodiments, single dosage of anti-CD20 antibody proteins (and / or a population thereof) are present in pharmaceutical formulations in a volume of about 0.5 mL to about 2 mL (e.g., 0.5 ml to 1 mL, 1.5 mL, 2 mL, 2.1 mL, or 2.25 mL)) in pre-filled syringes. In some embodiments, pre-filled syringes described here have a capacity of about 1 mL to about 2 mL (e.g., 1 mL; 1.25 mL; 1.5 mL; 1.75 mL; 2 ml, 2.25 mL, or 2.5 mL). In some embodiments, a dose of 2 mL is delivered.

[0110] In some embodiments, the present disclosure provides 25 mg / mL, 50 mg / mL, 100 mg / mL, 125 mg / mL, or (preferably) 150 mg / mL anti-CD20 antibody proteins (or a population thereof) in a pharmaceutical formulation in a volume of 1 mL, 2 mL, 3 mL, 4 mL, or 5 mL in pre-filled syringe (e.g., a pre-filled syringe with a capacity of 1 mL, 2 mL, 3 mL, 4 mL, or 5 mL). In some embodiments, the present disclosure provides 150 mg / mL anti-CD20 antibody proteins (or a population thereof) in a pharmaceutical formulation in a volume of about 1 mL to about 2 mL (e.g., 1 mL; 1.25 mL; 1.5 mL; 1.75 mL; 2 mL; 2.1 mL, or 2.25 mL) in a pre-filled syringe (e.g., a pre-filled syringe with a capacity of 5 mL). For example, a pre-filled syringe of the present disclosure can comprise a pharmaceutical formulation comprising about 150 mg / mL of the anti-CD20 antibody proteins (or a population thereof) in a total volume of 1 mL, 1.5 mL, or 2 mL.Attorney Docket No.50581-0016WO1 Pharmaceutical Formulation

[0111] Also disclosed here are pharmaceutical formulations comprising the compositions (e.g., the anti-CD20 antibody (e.g., ublitximab) protein compositions) provided herein. The anti- CD20 antibody proteins (or a population thereof) can be present in the pharmaceutical formulation at a concentration of about 25 mg / mL to 180 mg / mL (e.g., about 25 mg / mL to 170 mg / mL; about 25 mg / mL to 160 mg / mL; about 25 mg / mL to 150 mg / mL; about 50 mg / mL to 150 mg / mL; about 75 mg / mL to 150 mg / mL; about 100 mg / mL to 150 mg / mL; or about 125 mg / mL to 150 mg / mL (e.g., about 25 mg / mL; about 50 mg / mL; about 100 mg / mL; about 125 mg / mL; about 150 mg / mL; about 160 mg / mL; about 170 mg / mL; or about 180 mg / mL)). For example, provided herein is a pharmaceutical formulation comprising anti-CD20 antibody proteins (or a population thereof) at a concentration of about 25 mg / mL. Also, provided herein is a pharmaceutical formulation comprising anti-CD20 antibody proteins (or a population thereof) at a concentration of about 150 mg / mL.

[0112] Provided herein are pharmaceutical formulations comprising anti-CD20 antibody proteins (or a population thereof), wherein the anti-CD20 antibody protein (e.g., in the population) comprises ublituximab. In some embodiments, the anti-CD20 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2. Also, provided herein is a pharmaceutical formulation comprising anti-CD20 antibody proteins (or a population thereof), wherein the anti- CD20 antibody proteins in the population comprise: a VH comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:3, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:5; and / or a VL comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:8, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:9, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:10.

[0113] The pharmaceutical formulation can comprise one or more of the following excipients: sodium chloride, trisodium citrate dehydrate (also referred to herein as sodium citrate), polysorbate 80, and hydrochloric acid. The pharmaceutical formulation can comprise about 8-10 mg / mL, e.g., about 9.0 mg / mL of sodium chloride. The pharmaceutical formulation can comprise about 7-8 mg / mL, e.g., about 7.4 mg / mL of trisodium citrate dehydrate. The pharmaceutical formulation can comprise about 0.5-0.8 mg / mL, e.g., about 0.7 mg / mL ofAttorney Docket No.50581-0016WO1 polysorbate 80. The pharmaceutical formulation can comprise about 0.3-0.5 mg / mL, e.g., about 0.4 mg / mL of hydrochloric acid. The pharmaceutical formulation can comprise about 20-30 mM, e.g., about 25 mM sodium citrate. The pharmaceutical formulation can comprise about about 125-160 mM, e.g., about 154 mM sodium chloride. The pharmaceutical formulation can comprise about 0.05%-0.1%, e.g., about 0.07% polysorbate 80. The pharmaceutical formulation can have a pH of about 6-7, e.g., about 6.5. For example, a pharmaceutical formulation described herein can comprise about 20-30 mM (e.g., about 25 mM) sodium citrate, about 125- 160 mM (e.g., about 154 mM) sodium chloride, about 0.05%-0.1% (e.g., about 0.07%) polysorbate 80, and have a pH of about 6-7 (e.g., pH of about 6.5). In some instances, the pharmaceutical formulation comprises anti-CD20 antibody proteins (or a population thereof) at a concentration of about 150 mg / mL. In some instances, the pharmaceutical formulation comprises anti-CD20 antibody proteins (or a population thereof) at a concentration of about 25 mg / mL.

[0114] In some embodiments, in the methods of the present disclosure, the pharmaceutical formulation is administered by subcutaneous injection to a subject in need thereof. In some embodiments, in the methods of the present disclosure, the pharmaceutical formulation is administered by intravenous infusion to a subject in need thereof. In some embodiments, in the methods of the present disclosure, a pharmaceutical formulation comprising anti-CD20 antibody proteins (or a population thereof) at a concentration of about 150 mg / mL is administered by subcutaneous injection to a subject in need thereof. In some embodiments, in the methods of the present disclosure, a pharmaceutical formulation comprising anti-CD20 antibody proteins (or a population thereof) at a concentration of about 25 mg / mL is administered by intravenous infusion to a subject in need thereof. In some embodiments, the pharmaceutical formulation suitable for either subcutaneous or intravenous administrion comprises one or more of the following excipients: sodium chloride, trisodium citrate dehydrate, polysorbate 80, and hydrochloric acid (e.g., one or more of about 9.0 mg / mL of sodium chloride, about 7.4 mg / mL of trisodium citrate dehydrate, about 0.7 mg / mL of polysorbate 80, and 0.4 mg / mL of hydrochloric acid). In some embodiments, the pharmaceutical formulation suitable for either subcutaneous or intravenous administrion comprises one or more of the following excipients: sodium chloride, sodium citrate, and polysorbate 80 (e.g., one or more of about 25 mM sodium citrate, about 154 mM sodium chloride, and 0.07% polysorbate 80) and have a pH of about 6.5.Attorney Docket No.50581-0016WO1 SEQUENCE TABLEAttorney Docket No.50581-0016WO1Attorney Docket No.50581-0016WO1Attorney Docket No.50581-0016WO1Attorney Docket No.50581-0016WO1Attorney Docket No.50581-0016WO1

[0115] The following examples are offered by way of illustration, and not by way of limitation. 8. EXAMPLES 8.1 Example 1—Glycosylation Profile

[0116] The glycosylation profile of a sample of anti-CD20 antibody proteins provided herein was determined by measuring fluorescently labeled N-glycans (fluorescent label is 2- aminobenzamide) that were enzymatically cleaved from the anti-CD20 antibody proteins using PNGase F. The labeled glycans are resolved using a hydrophilic interaction column equipped. The glycans flow through a fluorescence detector after separation. Peak identification from the test sample chromatograms is identified based on retention time and relative to peaks in the glycan standard which have been confirmed by mass spectrometry. The relative percentage of each N-glycan is calculated based on the N-glycan peak area divided by the total peak area of all N-glycans. The glycosylation profile is shown in Figure 2. 8.2 Example 2—Intact mass method

[0117] The glycosylation profile of anti-CD20 antibody proteins provided herein was assessed by intact mass analysis (LC-MS) under non-reducing conditions. The sample of anti- CD20 antibody proteins provided herein is first exchanged into MS appropriate buffers during the chromatography step using SEC and a mobile phase containing TFA, acetonitrile, and water. The sample is then introduced into an ESI-QTOF for intact mass analysis. The mass spectra are deconvoluted and the peaks are assigned based on mass. The relative abundance of each anti- CD20 antibody proteins provided herein containing N-glycan was calculated by taking the abundance of an N-glycan and dividing by the total abundance of all identified peaks. Results are provided in the table below and in Figure 3.Attorney Docket No.50581-0016WO1 Table 1. Intact Molecular Weights for Sample of anti-CD20 antibody proteins by LC-MSAttorney Docket No.50581-0016WO1Abbreviation: ND = not detected. 8.3 Example 3—Commercial-Scale Manufacturing Process of Making TG-1101 in YB2 / 0 Rat Hybridoma Cells

[0118] In this Example, the manufacturing process for TG-1101 expressed inrat hybridoma cells at 15,000 L is described.

[0119] The host cell line used for generation of the TG-1101 producing cell line was the rat cell line YB2 / 0. The production cell line, R603-12D11, was developed after transfecting the expression vector HK463-25 (containing the immunoglobulin heavy and light chain cDNA sequences of TG-1101) into the YB2 / 0 host cell line. Figure 4 depicts the expression vector map of HK463-25 to produce TG-1101, in a 15,000 L bioreactor. An overview of the manufacturing process for TG-1101 is illustrated in the flow diagram of Figure 5.

[0120] In summary, the production of each batch of TG-1101 began with the thaw of a working cell back (WCB) vial. The culture was expanded through a series of shake flasks and seed bioreactors to meet the inoculum requirements of the 15,000 L production bioreactor, which was operated in fed-batch mode. The bioreactor was harvested and clarified by centrifugation followed by depth filtration. The clarified harvest was purified by three chromatography steps including Protein A, cation exchange, and anion exchange, designed to purify the TG-1101 and to reduce process impurities such as host cell protein and residual DNA. The purification process contained steps to ensure viral safety including viral inactivation (solvent / detergent) and a viralAttorney Docket No.50581-0016WO1 filtration step. Final ultrafiltration / diafiltration (UFDF) and formulation steps were used to concentrate and buffer exchange TG-1101 into the formulation buffer and to the desired product concentration. The ready to fill drug substance was formulated to obtain TG-1101 at a concentration of 25.0 mg / mL in 25 mM sodium citrate, 154 mM sodium chloride, 0.07% polysorbate 80, pH 6.5. After filling, the TG-1101 drug substance was frozen at -60°C and then stored frozen at -35°C.

[0121] Descriptions of the manufacturing process are provided, e.g., in U.S. Patent No. 11,884,740, U.S. Patent No. 11,807,689, U.S. Patent No.11,814,439, and U.S. Patent Appln. No. 18 / 167,631, the entire contents of each of which are incorporated by reference herein. 8.4 Example 4— Pharmacokinetic / pharmacodynamic evaluation of a single intravenous or subcutaneous dose of ublituximab in patients with multiple sclerosis

[0122] This Example describes a 120-week, Phase 1 multi-center study designed to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), safety, and tolerability of ublituximab in patients newly starting ublituximab treatment. The subcutaneous administration of ublituximab is currently being evaluated in a Phase 1 study. It is a 2-part study which is evaluating the bioavailability and tolerability of ublituximab administered subcutaneously in patients with relapsing forms of multiple sclerosis (RMS).

[0123] In Part 1, the PK / PD, safety and tolerability of a single subcutaneous (SC) dose of ublituximab on Day 1 is evaluated followed by intravenous (IV) dosing of 450 mg IV on Day 15, Week 24 and every 24 weeks thereafter in line with the approved BRIUMVI IV dose regimen. The SC dose administered on Day 1 was dose escalated in cohorts ranging from 50 mg SC to 300 mg SC.

[0124] In Part 2, the PK / PD, tolerability, safety, and efficacy of a fully subcutaneous regimen of ublituximab is evaluated, with subcutaneous doses administered every 8 or 12 weeks after the initial doses on Day 1 and Day 15. Rationale for the Study

[0125] Ublituximab is a type I chimeric IgG1 monoclonal antibody that selectively binds to the trans-membrane CD20 antigen found on CD20 expressing B-lymphocytes. Ublituximab is glycoengineered, producing a low fucose content in its fragment crystallizable (Fc) region. TheAttorney Docket No.50581-0016WO1 exclusion of specific fucose molecules in the Fc region enhances its affinity for all variants ofFc RIIIa receptors, activates natural killer (NK)-cell function and results in enhanced antibody-dependent cellular cytotoxicity (ADCC) relative to other approved anti-CD20 antibodies. In in vitro studies, ublituximab demonstrated 25 to 30 times increased ADCC relative to other anti- CD20 therapies. See, Alvarez, E. et al. Reduced Disease Progression With Ublituximab vs Teriflunomide in the Phase 3 ULTIMATE I and II Studies in Relapsing Multiple Sclerosis. In: CMSC (2022).

[0126] Two identical, randomized, active-controlled studies (ULTIMATE I and ULTIMATE II) demonstrated significant efficacy outcomes of ublituximab versus teriflunomide in relapsing multiple sclerosis (RMS). See, Steinman, L. et al., N Engl J Med.387(8):704-714 (2022). Particularly, ublituximab treatment was associated with a 54% relative reduction in annualized relapse rate (ARR) compared to teriflunomide, and approximately 96% and 91% relative reductions in T1 gadolinium (Gd)-enhancing lesions and new or enlarging T2 lesions (all significant), respectively.

[0127] Based on these studies, the FDA-approved administration schedule of ublituximab is as follows: 150 mg initial dose on Day 1 (4-hour intravenous (IV) infusion) followed by a 450 mg dose on Day 15 (1 hour IV infusion), and 450 mg (1 hour IV infusion) every 24 weeks thereafter.

[0128] To increase treatment options available to patients and physicians, a subcutaneous (SC) formulation of ublituximab has been developed. The pharmacokinetic (PK) and pharmacodynamic (PD) of a single initial dose of SC ublituximab and a single initial dose of IV ublituximab is being assessed in multiple sclerosis (MS) patients previously untreated with ublituximab. Study Objectives PART 1: Initial Dose SC Replacement PK / PD

[0129] Primary Objectives: To assess the PK and relative bioavailability of IV and SC ublituximab To assess the PD of IV and SC ublituximab

[0130] Secondary Objectives: To assess the safety and tolerability of IV and SC ublituximabAttorney Docket No.50581-0016WO1 PART 2: Full Subcutaneous Regimen PK / PD

[0131] Primary Objective To assess the pharmacokinetics of ublituximab when administered subcutaneously every 12 weeks

[0132] Secondary Objectives To assess the pharmacodynamics of ublituximab when administered subcutaneously every 12 weeks To assess the safety and tolerability of ublituximab when administered subcutaneously every 12 weeks To assess the clinical efficacy of ublituximab when administered subcutaneously every 12 weeks Endpoints PART 1: Initial Dose SC Replacement PK / PD

[0133] Primary Endpoints: 1. Area under the curve (AUC)(0-D14) following Dose 1 SC or IV 2. Percentage of patients with CD19+ B cell counts 10 cells / μL at Day 15 pre-dose

[0134] Secondary Endpoints: 1. Other PK parameters following Dose 1 and Dose 2 2. Percentage of participants with CD19+ B cell counts 10 cells / μL at Week 24 3. Incidence of all grades and Grade 3 adverse events (AEs) during the 120-week study duration 4. Percentage of participants with all grades and Grade 3 injection / infusion related reactions (IRR; local or systemic) following SC or IV administration at Day 1 and IV administration on Day 15 PART 2: Full Subcutaneous Regimen PK / PD

[0135] Primary Endpoint 1. AUC(0-W24)

[0136] Secondary EndpointsAttorney Docket No.50581-0016WO1 1. Other PK parameters throughout the study 2. Percentage of participants with CD19+ B cell counts 10 cells / μL at prespecified timepoints during the 108-week study duration 3. Incidence of all grades and Grade 3 adverse events (AEs) during the 108-week study duration 4. Percentage of participants with all grades and Grade 3 injection related reactions (local injection site reactions or systemic injection reactions)

[0137] Additional Secondary Endpoints for Participants with RMS 1. The proportion of participants with no change or reduction in number of T1 Gd- enhancing lesions from baseline to Week 48 2. The proportion of participants free of T1 Gd-enhancing lesions at Week 48 Study Design PART 1: Initial Dose SC Replacement PK / PD

[0138] This is a 120-week, Phase 1 multi-center study designed to evaluate the PK, PD, safety, and tolerability of ublituximab in patients newly starting ublituximab treatment. The study evaluates different cohorts of participants receiving an initial dose of either IV or SC ublituximab followed by subsequent doses of IV ublituximab in line with the dosing regimen outlined in Table 2 below. The dose of SC ublituximab is escalated (see Table 2) and then refined to assess tolerability, PK and PD. Table 2. Part 1 Initial Dose EscalationAttorney Docket No.50581-0016WO1Note: Total number of participants enrolled in each cohort and the advancement of cohorts will be based on tolerability and / or PK / PD considerations. SC1 through SC5 will be enrolled sequentially. IV cohort may enroll intermittently at times when SC cohorts are not open for enrollment. Not all cohorts may be opened for enrollment based on PK / PD and safety considerations and cohorts may be expanded as needed.

[0139] Participants are assigned to a cohort during the screening period, starting at the 50 mg SC dose and escalating through the first five SC cohorts as shown in the table above. PK, PD and safety data (i.e., incidence, severity, and type of local and systemic IRRs) are continuously reviewed from all cohorts. Enrollment into cohorts is initiated based on the Sponsor’s and / or treating physician’s assessment of tolerability, PK and PD data. Following dosing of the first participant in SC1 through SC5, a 48-hour observation period to review safety and tolerability data is utilized before dosing subsequent participants in the same cohort. Study duration is expected to be 120 weeks and will include PK, PD and safety assessments throughout.

[0140] The Principal Investigator (PI) and / or Treating Neurologist (TN) will be responsible for participant eligibility evaluation, supervision of study drug administration, assessment, and treatment of adverse events (AEs), and monitoring of safety assessments, including laboratory results.

[0141] Subsequently, PK / PD modeling will be performed to determine a SC dose of ublituximab that demonstrates PK bioequivalence to the 150 mg ublituximab IV dose. If the model-informed bioequivalent SC dose was not previously evaluated in cohorts SC1 – SC5, PK will be confirmed by enrolling 6-12 participants into an intermediate cohort (Model Informed [MI] dose), selected from among the doses in the table below. Upon confirmation of bioequivalence, expansion of the MI dose cohort may continue with a reduced PK sampling schedule, enrolling up to 50 additional RMS participants at the selected bioequivalent dose.Attorney Docket No.50581-0016WO1 Table 3. Part 1 Dose Confirmation and ExpansionNOTE: If the model informed bioequivalent dose is determined to be one of the doses evaluated in SC1-SC5, the PK Confirmation cohort will not be enrolled. Instead, participants may be enrolled at the model informed dose level directly into the Expansion (reduced PK) cohort.

[0142] Participants may be screened up to 28 days prior to the first dosing date (Day 1). Study duration is expected to be 120 weeks. PART 2: Full Subcutaneous Regimen PK / PD

[0143] This is a 108-week, Phase 1 single-arm multi-center study designed to evaluate the PK, PD, safety, tolerability, and efficacy of a fully subcutaneous dosing regimen of ublituximab in participants with RMS who are newly starting ublituximab treatment.

[0144] Part 2 leverages PK / PD and tolerability data generated in Part 1 to evaluate a fully SC dose regimen of ublituximab that is expected result in similar exposure across 24 weeks to the approved IV regimen. Assuming dose linearity and no accumulation, two 225 mg IV doses administered 12 weeks apart are expected to match the exposure of a single 450 mg IV dose across 24 weeks. Therefore, an SC dosing regimen expected to be bioequivalent to 225 mg IV, administered every 12 weeks following the initial doses on Day 1 and Day 15, was evaluated in Part 2.

[0145] On Day 1, participants received the SC dose of ublituximab which has been identified in Part 1 to be bioequivalent to 150 mg IV.

[0146] On Day 15, Week 12 and every 12 weeks thereafter up to Week 96, SC doses were approximately 1.5 times the dose administered on Day 1 resulted in exposures comparable to 225 mg administered intravenously. Assuming the bioavailability of subcutaneous ublituximabAttorney Docket No.50581-0016WO1 administration is between 50-85%, the model-informed bioequivalent dose administered every 12 weeks subcutaneously was between 265 and 450 mg. The exact dose was confirmed upon modeling of the PK data obtained in Part 1, and was communicated to sites upon opening of Part 2.

[0147] The dosing schedule for Part 2 followed the regimen outlined in the table below. Approximately 6-12 participants were enrolled initially to confirm the PK of the proposed subcutaneous dosing regimen. Additional participants may be enrolled in an expansion cohort with reduced PK sampling to further evaluate safety and efficacy. Table 4. Part 2 Study Design

[0148] Participants may be screened up to 28 days prior to the first dosing date (Day 1). Study duration is expected to be 108 weeks. Study Duration

[0149] The study is expected to take approximately 4 years to complete. This includes an estimated 18 months of enrollment and 120 weeks of study duration for Part 1 and 108 weeks for Part 2. The study will end at the Last Patient Last Visit (LPLV) although the primary analysis for Part 1 and Part 2 will take place after evaluable subjects complete the Week 24 visit. MS Inclusion Criteria

[0150] MS Participants must meet all of the following inclusion criteria to be eligible for participation in this study: 1. 18-65 years old 2. Diagnosis of RMS (2017 Revised McDonald criteria)Attorney Docket No.50581-0016WO1 3. Expanded Disability Status Scale (EDSS) score 5.5 at screening 4. Neurologically stable for > 30 days prior to Day 1 5. IgG > 4.0 g / L at screening 6. Female participants of childbearing potential must consent to use an effective method of contraception from consent and for 6 months after the last dose of ublituximab. MS Exclusion Criteria

[0151] MS participants who meet any of the following exclusion criteria are not eligible to be enrolled to this study: 1. Primary-progressive MS (PPMS) or inactive Secondary Progressive MS (SPMS) 2. Active chronic (or stable but treated with immune therapy) disease of the immune system other than MS (e.g., rheumatoid arthritis, scleroderma, Sjögren's syndrome, Crohn’s disease, ulcerative colitis, etc.) or immunodeficiency syndrome (hereditary immune deficiency, drug-induced immune deficiency, etc.) 3. Participants with CD19+ B-cell count below 40 cells / μL at screening 4. Participants who previously received anti-CD20 therapy and discontinued treatment due to safety reasons or lack of efficacy 5. Participants who previously received any approved therapy to treat MS within 5 half- lives of the medication prior to Day 1; or who have ever received ublituximab, alemtuzumab, cladribine, cyclophosphamide, mitoxantrone, or daclizumab. 6. Treatment with any investigational agent within 5 half-lives of the investigational drug prior to Day 1, or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency) 7. History of life-threatening injection / infusion related reaction (IRR), hypersensitivity, or anaphylactic reaction with anti-CD20 therapy, components of ublituximab solution or pre-treatment medications 8. Current evidence or known history of clinically significant infection, including: chronic, recurrent, or ongoing active viral, bacterial, or fungal infectious disease requiring long term systemic treatment such as, but not limited to chronic urinary tract infection, chronic pulmonary infection with bronchiectasis, tuberculosis, or active hepatitis C virus (HCV)Attorney Docket No.50581-0016WO1 9. History of serious opportunistic or atypical infections, including human immunodeficiency virus (HIV) 10. History of active hepatitis B virus (HBV) as evidenced by a detectable hepatitis B surface antigen (HBsAg) or positive hepatitis B core antibody (HBcAb), or chronic hepatitis C infection. Participants with positive hepatitis C virus antibody (HCV Ab) are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA) 11. History or evidence (clinical, radiological, or biomarker) of suspected or confirmed progressive multifocal leukoencephalopathy (PML) 12. Receipt of any live or live-attenuated vaccines (including vaccines for varicella-zoster virus or measles) within 4 weeks prior to first study drug administration 13. Participants exposed to corticosteroids (not including steroids used for premedication) received within 30 days prior to Day 1, including topical and inhaled steroids. 14. Participants requiring treatment with intravenous immunoglobulin (IVIG) for decreased immunoglobulins within the 12 months prior to Day 1 15. Any severe or uncontrolled medical condition that could affect the participant’s ability to participate 16. Females who are pregnant or nursing 17. History of cancer except: a. If considered likely to be cured (with supporting documentation from the treating oncologist if possible) b. Is not being actively treated with anti-cancer therapy or radiotherapy and, in the opinion of the Investigator, is not likely to require treatment in the ensuing 3 years c. Considered to have low probability of recurrence (with supporting documentation from the treating oncologist if possible) d. Adequately treated and / or resolved basal or in situ squamous carcinomas of the skin are permitted 18. Unwillingness or inability to comply with study and / or follow-up procedures outlined in the protocol. Laboratory Evaluations

[0152] For PK analyses on peripheral blood samples, blood samples will be collected and sent to the central laboratory to measure the concentration of ublituximab at specified timepoints after dose administration. Blood samples should be drawn from all participants at the study timepoints described in Table 5 below.Attorney Docket No.50581-0016WO1 Table 5. Timepoints for PK collections

[0153] For PD analyses on peripheral blood samples, blood samples for CD19+ B cell counts will be drawn at screening, Days 3 (SC cohort only), 7, 15 (pre-dose), and 22, and pre-dose on Weeks 24, 48, 72, and 96 as well as at Week 120 / end of study (EOS). Blood collection for immunogenicity anti-drug antibody (ADA) analyses will be performed pre-dose at Days 1 and 15, and pre-dose on Weeks 24, 48, 72, and 96 as well as at Week 120 / EOS. Study Drug Ublituximab Packaging and Labeling

[0154] Ublituximab will be provided to the study site in two formulations: 25 mg / mL (150 mg / 6 mL in single-use vial) solution for infusion for IV administration 150 mg / mL (300 mg / 2 mL in single-use vial) solution for injection for SC administrationAttorney Docket No.50581-0016WO1 Ublituximab IV Administration

[0155] Ublituximab IV should be administered intravenously through a dedicated line. No other treatment may be co-administered with ublituximab. Ublituximab should only be diluted in 250 mL 0.9% NaCl before use. No data are available for other solutions such as 5% dextrose and 5% mannitol. Ublituximab IV should not be administered as an IV push or bolus. Storage Instructions for the Prepared IV Solution

[0156] The prepared infusion solution should be used immediately. If the diluted solution is not administered immediately, it can be stored refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours. It cannot be frozen. If the diluted solution is stored refrigerated, it has to be equilibrated to room temperature prior to administration (approximately 2 hours). The diluted solution can be stored for an additional 8 hours at room temperature up to 25°C (77°F), which includes the equilibration time and infusion time. Dilutions

[0157] Dilution calculations are shown in Table 6 below. Table 6. Ublituximab vials containing 25 mg / mL (150 mg / 6 mL in 10 mL single-use vial)Infusion Rates

[0158] Ublituximab IV should be administered only by slow infusion via intravenous route as a single administration as described in Table 7 and Table 8 below: Table 7. First Ublituximab Infusion (Day 1, Cohort IV only)Attorney Docket No.50581-0016WO1 Table 8. Subsequent Ublituximab Infusions (Day 15 and Weeks 24, 48, 72 and 96; all Cohorts)Ublituximab SC Administration

[0159] Ublituximab SC (150 mg / mL) must be administered as a subcutaneous injection by the PI, TN, or a designee. Site of Administration: Lower abdomen at least 2 inches from navel. Ublituximab should be injected into the subcutaneous tissue of the lower abdomen. Do not administer in an area where there is bruising, redness, tenderness, hardness, or near a mole, scar or stretch marks. Injection site location must be recorded in the eCRF. Ublituximab should not be self-administered. Prepared SC syringe is to be used immediately. Preparation

[0160] Ublituximab SC should be prepared and administered by subcutaneous injection as a single administration as described in Table 9 below. The vial should be allowed to reach room temperature prior to administration. Withdraw the required volume from the vial using the specified size sterile syringe. Immediately prior to the SC injection, change the needle to the size specified for the SC injection. Administer the SC injection at an approximate 45 degree angle slowly and evenly, without force. Do not massage or rub the injection site after administration. Table 9. Ublituximab vials containing 150 mg / mL (300 mg / 2 mL in 2 mL single-use vial) for SC injectionAttorney Docket No.50581-0016WO1*Any length sterile needle may be used to withdraw ublituximab from the vial. Statistical Considerations

[0161] The primary purpose of this study is to evaluate tolerability of SC dosing at different levels and an exploratory characterization the PK and PD of ublituximab after a single dose given either via IV or SC administration. Given the low inter-individual variability in ublituximab PK at the approved IV regimen (AUC coefficient of variance = 28%; CmaxCV% = 15%), sample sizes of 6-12 participants are expected to provide a reasonable characterization of ublituximab PK following single SC doses and to enable an exploratory comparison to IV PK at the approved dose planned in this study. The proposed sample size is also generally consistent with similar studies intended to explore PK comparability of different dose routes for monoclonal antibodies. Participants who drop out prior to the dose on Day 15 may be replaced at Sponsor discretion.

[0162] The Safety Population will include all participants who received at least one dose of ublituximab.

[0163] An accounting of the study participants will be tabulated. Participants that do not complete the study will be listed along with the reason for their discontinuation and reasons for discontinuation will be summarized.

[0164] Baseline demographic and clinical characteristics will be summarized as percentages for categorical variables and as mean, standard deviation (SD), median, minimum, and maximum for continuous measures.

[0165] Extent of Exposure: The dose (mg) of study drug administered, the total number of doses of study drug, and the duration of treatment will be summarized with descriptive statistics.Attorney Docket No.50581-0016WO1 Pharmacokinetic Analyses

[0166] All participants who receive at least one dose of ublituximab and have at least one measurable ublituximab concentration with associated dosing time and dosing information, without major deviations, will be included in the PK analysis population.

[0167] Pharmacokinetic measures including but not limited to AUC0-14d, Cmax, Tmax, Clast, AUClast, Tlast, and Ctrough,Day 15,and SC bioavailability will be estimated as data permit via non- compartmental analyses. Geometric mean ratios of the primary study endpoint AUC0-14dafter dosing on Day 1 in SC treatment cohorts vs Cohort IV will be calculated along with the associated 90% confidence intervals (CI). Similar calculations may be conducted for Cmaxafter dosing on Day 1.

[0168] Additionally, PK data from this study may be incorporated into a population PK model for further analysis to aid the design of future trials. The results from these analyses will be reported separately. Pharmacodynamic Analyses

[0169] Pharmacodynamic measures will be analyzed on all participants with one or more post baseline sample(s).

[0170] For the following proportion endpoint, the number and percent of participants of interest will be calculated along with exact (Clopper-Pearson) two-sided 95% CI. Proportion of participants with B-cells 10 cells / μL at Day 3, Day 7, Day 15, Day 22, Week 24, Week 48, Week 72, Week 96, and Week 120 / EOS.

[0171] For the following continuous endpoint, descriptive statistics (n, mean, SD, median, Q1, Q3, minimum, and maximum) will be provided for baseline, Day 3, Day 7, Day 15, Day 22, Week 24, Week 48, Week 72, Week 96, and Week 120 / EOS as well as the changes from baseline: CD19+ B-cell counts Safety Analyses

[0172] Safety will be analyzed on the Safety population, by cohort. Safety analyses will be primarily based on the incidence, seriousness, and severity of AEs (including local and systemicAttorney Docket No.50581-0016WO1 IRRs) and supplemented by clinically meaningful laboratory results, physical examination, and vital signs, as available.

[0173] Detailed information collected for each AE will be included in a listing: adverse event term, start / stop dates of the AE, seriousness, severity, relationship to study drug, action taken, and outcome. In addition, the number and percentage of participants experiencing at least one treatment-emergent AE will be tabulated by body system, preferred term, and CTCAE grade. Treatment-emergent AEs, drug-related AEs, adverse events of special interest, SAEs, AEs with a fatal outcome, and AEs leading to discontinuation / dose modification will be further summarized. Immunogenicity Analyses

[0174] All participants who received at least one ublituximab dose and had at least one post- baseline ADA sample, without major deviations will be included in the immunogenicity analysis population. Anti-ublituximab antibody measures (% TE-ADA positive participants, titer values, % nAb positive) will be described at each measured time point and by cohort. The impact of anti-ublituximab antibody development on the PK, PD and safety of ublituximab may be explored. Additional analyses of PK and PD data excluding participants positive for anti- ublituximab antibodies may be conducted as appropriate. 8.5 Example 5— Evaluation of bioavailability and tolerability of ublituximab administered subcutaneously in patients with multiple sclerosis

[0175] The subcutaneous administration of ublituximab is currently being evaluated in a Phase 1 study. A synopsis of the study is provided in Example 4. A summary of the results available to date are provided in this Example. Disposition and Demographics

[0176] In Part 1, 56 participants have been enrolled (Table 10) and 13 participants have been enrolled in Part 2 (Table 11). Demographics of the participants are described in Table 12. Among the participants treated to date, 66 participants have RMS.Attorney Docket No.50581-0016WO1 Table 10. TG1101-RMS-SC101 Part 1 Enrollment SummaryData cutoff: 21 February 2025 Table 11. TG1101-RMS-SC101 Part 2 Enrollment SummaryTable 12. TG1101-RMS-SC101 Part 1 and Part 2 DemographicsSafety

[0177] In Part 1, the safety of subcutaneous ublituximab injections were evaluated in Cohorts SC1 – SC5, with a single subcutaneous injection administered on Day 1. On Day 15 and onwards, all participants in Part 1 received IV infusions of ublituximab per the approved label regimen. Among these cohorts, injection related reactions (systemic) were observed in 1 participant treated at 150 mg and 2 participants treated at 300 mg SC, and injection site reactionAttorney Docket No.50581-0016WO1 (local) was reported in 1 participant treated at 300 mg. These local and systemic injection related events were all Grade 1 or 2 in severity and resolved. Overall, SC injections were well tolerated in these cohorts.

[0178] In Part 2, multiple injections of subcutaneous ublituximab were evaluated in a fully subcutaneous regimen with 300 mg administered on Day 1, and 400 mg administered on Day 15, Week 12 and every 12 weeks thereafter. Among the 13 participants treated in Part 2, four (4) reported systemic injection related reactions, all of which were Grade 1 and 2 in severity and resolved. No local injection site reactions were reported.

[0179] Overall, in both Part 1 and Part 2, there have been no AEs leading to drug discontinuation, no AEs leading to death, and no pregnancies have reported. All AEs reported to date have been Grade 1, 2 or 3 in severity, with no Grade 4 or 5 events observed. One serious adverse event (SAE) of a Grade 3 perianal abscess with intercostal fistula was reported in a participant in cohort SC5. This event was not considered related to ublituximab treatment, resolved and no action was taken with study drug.

[0180] Table 20 lists all the Treatment Emergent Adverse Events (TEAEs) reported on study with an incidence 2 participants. The most commonly occurring TEAEs were injection related reactions (21%) and infusion related reactions (11%). Injection related reactions were considered to be any systemic adverse events generally occurring within 24 hours of a subcutaneous injection that the investigator determined was attributable to the injection. Infusion related reactions were considered to be any systemic adverse events generally occurring within 24 hours of an infusion that the investigator determined was attributed to the infusion. Injection site reactions were any events occurring locally after a subcutaneous injection and only one event of injection site pain, Grade 1, was observed in 1 participant treated at 300 mg (not presented in Table 13). Table 13. All TEAEs in Study TG1101-RMS-SC101 with an incidence 2 participantsAttorney Docket No.50581-0016WO1Data cutoff: 21 Feb 2025 *Of note, per protocol, pre-medications for 3 participants in the Part 1 SC expansion cohort were reduced on Day 1 to assess a modified premedication regimen. All 3 participants experienced an injection related reaction on the Day 1 injection. All remaining participants on study were treated with the full premedication regimen of corticosteroids, antihistamine and antipyretic on Day 1. Pharmacodynamics

[0181] At all SC doses evaluated to date, the intended pharmacodynamic effect of CD19+ B- cell depletion was observed after a single dose by Day 3 and depletion of cells was maintained through Day 15 when the next ublituximab dose was administered (Table 14). Table 14. Median CD19+ B-cell counts (cells / μL) of participants treated in Part 1 and Part 2Attorney Docket No.50581-0016WO1Data cutoff: 21 Feb 2025. NC = not collected Pharmacokinetics

[0182] After a single subcutaneous dose of ublituximab, approximate dose-dependent increases in exposure between 50 mg to 300 mg SC were observed in cohorts SC1 – SC5 (Figure 6 and Figure 7). The Cmax was significantly lower with SC administration when compared to IV administration. Absorption of the subcutaneous dose could only be evaluated up to Day 15 in Part 1 prior to the administration of the IV dose of 450 mg. Based on GoF plots and visual predictive checks, the existing population PK model for the RMS population is well suited to describe the Phase 1 data. The estimated bioavailability given the study design limitations of Part 1 is currently 49%. To date, no clinically significant covariates have been identified for IV or SC administration. 8.6 Example 6— Pharmaceutical development of ublituximab solution for injection Formulation Development

[0183] A drug product formulation was developed for ublituximab at 25 mg / mL to ensure protein structural integrity and stability. The buffered formulation contains sodium chloride to adjust the product to isotonic conditions. Polysorbate 80 is added as a surfactant to minimize protein aggregation. The ublituximab solution for injection formulation at 150 mg / mL ublituximab (25 mM sodium citrate, 154 mM sodium chloride, and 0.07% polysorbate 80, pH 6.5) uses that same formulation.Attorney Docket No.50581-0016WO1

[0184] The development results confirmed the suitability of buffer and excipient formulation of 25 mM sodium citrate dihydrate, 154 mM sodium chloride, and 0.07% polysorbate 80 at pH 6.5 for the 25 mg / mL formulation.

[0185] The objective of the 150 mg / mL formulation was to provide a higher product concentration more suitable for subcutaneous administration. Development studies were conducted on the 150 mg / mL formulation to confirm stability of the product after freeze / thaw to support a frozen drug substance storage condition. Thermal stability studies were also conducted to support the 150 mg / mL formulation. These development studies included assessment of ublituximab high concentration quality at higher product concentrations (120, 150 and 180 mg / mL target concentrations) after multiple freeze / thaw cycles, agitation assessment, and in an accelerated stability study performed at higher storage temperatures. Results from these studies provide confirmation that the 150 mg / mL formulation is suitable for use at the drug substance and drug product intended storage conditions. Feasibility of a 150 mg / mL Clinical Formulation

[0186] Initial formulation development was performed to assess the feasibility of higher concentrated ublituximab. TG1101 was concentrated using Amicon Ultra-4 centrifugal filters system with a cutoff membrane of 30 kDa. Samples were centrifuged at 4°C (2800 x g) and concentration checked using SoloVPE until the 5 target concentrations were reached (125, 150,175, 200 and 225 mg / mL). Samples were then filtered using 0.22 m syringe-filters and PS80was spiked-in to final concentration 0.07%. Table 15 summarizes the source starting material and achieved concentrations through the formulation preparation phases. Table 15. Formulation Feasibility- Source Material and Concentration at each StepAttorney Docket No.50581-0016WO1

[0187] All formulations were slightly opalescent and visible particle / precipitate-free. The samples were then subjected to a viscosity assessment. Viscosity was measured using Rheosense microVISC with 0-100 cp and 10-1000 cp chambers and the N7.5 and N44 standards. The viscosity in the formulation increases exponentially with TG1101 concentration as illustrated in Figure 8 and Table 16. For concentrations above 170 mg / mL, the viscosity of the formulation was above 20 cp, the ascribed upper limit for the formulation assessment. Additionally, size exclusion chromatography was performed to establish an understanding of the concentration effects on the dimer species. Indeed, an increase in dimer species from the starting material was observed. Based on this data the following concentration range was further explored 120 – 180 mg / mL. Table 16. Formulation Concentration and ViscosityDevelopment of the 150 mg / mL Clinical Formulation

[0188] A higher concentration formulation was developed to optimize the clinical configuration for subcutaneous administration. The higher concentration would allow for a single vial to be used during clinical administration to the patient which is recommended in the June 2015 Guidance for Industry document “Allowable Excess Volume and Labeled Vial Fill Size in Injectable Drug and Biological Products.” Development studies were conducted to determine if the product concentration could be increased. Also, a study was performed to confirm stability of the product after freeze / thaw to support a frozen drug substance storage condition. The studies were performed using the same excipients and excipient concentrations used previously for the 25 mg / mL clinical formulation. The development studies included assessment of ublituximab product quality at 150 mg / mL, after multiple freeze / thaw cycles, afterAttorney Docket No.50581-0016WO1 72 h agitation, and in an accelerated stability study performed at higher storage temperatures. Results are discussed below. Freeze / Thaw Studies

[0189] In this study, formulations prepared as described in the stability setup section were subjected to five freeze-thaw cycles. A cycle consisted of freezing the formulation at -80°C overnight and thawing on the benchtop at RT for at least 3 hours. Appearance, soluble aggregate concentration by A280, charged variants by icIEF, purity using reducing and non-reducing CE and insoluble aggregates by MFI.

[0190] Physical appearance was noted for samples from vials that underwent five freeze / thaw cycles. The freeze / thaw study showed no change in the appearance of all samples as they all have a similar light amber color and opalescence to the t=0 samples.

[0191] The samples were analyzed using the MFI to quantitate and identify particles. Briefly, the MFI was purged with 0.19 mL followed by a 0.30 mL run. The particle count data is shown in Table 17. The particles observed have the typical morphology of protein aggregate and precipitate.

[0192] Results are shown for the selected 150 mg / mL formulation concentration in Table 17. The results show no significant changes are observed in the product quality attributes tested, except for subvisible particles. The results for subvisible particles show an increase with cycle number, however all results remain within acceptable levels for release test acceptance criteria through the three freeze / thaw cycles tested. The results from the other concentrations up to 180 mg / mL were similar (data not shown), with no impactful differences observed in quality attributes relative to the initial test sample. The freeze / thaw data results provided acceptable support for the selected 150 mg / mL formulation and long-term storage of ublituximab high concentration at -35°C.Attorney Docket No.50581-0016WO1 Table 17. Pilot Freeze / Thaw Study for Ublituximab Solution for Injection Concentrated to 150 mg / mLAbbreviations: HC = heavy chain; LC = light chain; IgG = immunoglobin G; iCIEF = imaged capillary isoelectric focusing; pI = isoelectric point; SEC = size-exclusion chromatography Agitation

[0193] Prepared formulations were placed on an orbital shaker at 500 rpm at room temperature for 72 hours. Appearance and soluble aggregates were monitored at 24, 48 and 72 hours. Each formulation underwent further analytics at the 72-hour timepoint: concentration by A280, charged variants by icIEF, purity using reducing and non-reducing CE and size exclusion chromatography, and insoluble aggregates by MFI. Results are shown in Table 18.Attorney Docket No.50581-0016WO1 Table 18. Pilot Agitation Study for Ublituximab Solution for Injection Concentrated to 150 mg / mLAccelerated Stability Study

[0194] The 150 mg / mL ublituximab solution for injection formulation was evaluated in a short-term stability study. The formulation was assessed after storage at accelerated (25°C) and stressed (40°C) conditions for up to 2 months. The results are shown in Table 19 for 25°C and Table 20 for 40°C.

[0195] The results for the 150 mg / mL concentration stored at 25°C show a 0.6% decrease in the reduced purity of ublituximab solution for injection. A small 0.4% increase in dimer was noted in the SEC assay. Subvisible particles increased significantly over 2 mo.

[0196] Trends were more pronounced at the 40°C storage condition as each assay showed changes over the 2-month testing.Attorney Docket No.50581-0016WO1 Table 19. Stability Study Results for 150 mg / mL Ublituximab at 25°CTable 20. Stability Study Results for 150 mg / mL Ublituximab at 40°CAttorney Docket No.50581-0016WO1aNot suitable for MFI analysis due to increased opalescence Conclusion for the Clinical Formulation (150 mg / mL)

[0197] The freeze / thaw and agitation study results support the product concentration for the drug substance and drug product formulation at 150 mg / mL. Acceptable results were observed after multiple freeze / thaw cycles and support a frozen drug substance storage condition. Accelerated and stressed stability studies were conducted, and the results confirmed that the 150 mg / mL condition is suitable for use. These results support the recommended storage of the drug substance at -35°C and the drug product at 2-8°C. Physicochemical and Biological Properties

[0198] Ublituximab solution for injection contains ublituximab high concentration at 150 mg / mL at a pH of 6.5. The selected pH condition and formulation excipients were designed to ensure the stability, quality, and purity of the antibody. The specification and test methods were selected to ensure the identity, quality, purity, biological activity, and safety of the production and consider the physiochemical and biological properties of the product. Physical properties based on the formulation are provided in Table 21. Table 21. Physical properties of 150 mg / mL Ublituximab Solution for InjectionAttorney Docket No.50581-0016WO18.7 Example 7— Description and Composition of the Drug Product Description and Composition of Ublituximab Solution for Injection

[0199] Ublituximab solution for injection is a sterile solution containing 150 mg / mL of ublituximab. The product is a single use vial designed only for subcutaneous injection.

[0200] Each vial of drug product contains 150 mg in a 1 mL solution in a single-use vial. The composition is provided in Table 22. Table 22. Composition of Ublituximab, Solution for InjectionaFormula weight is based on dihydrate formbContains 2.4 mg hydrochloric acid 6MAttorney Docket No.50581-0016WO1

[0201] Ublituximab solution for injection is filled in Type I, colorless glass vials with siliconized chlorobutyl rubber stoppers that contain a barrier film and sealed with aluminum caps with a plastic button. Description and Composition of Ublituximab Injection for IV Administration

[0202] Ublituximab injection for IV administration is a sterile solution containing 25 mg / mL of ublituximab. The product is a single use vial designed only for intravenous use after dilution in 0.9% sodium chloride.

[0203] Each vial of drug product contains 150 mg / 6 mL solution in a single-use vial. The composition is provided in Table 23. Table 23. Composition of Ublituximab, Injection for IV Administration1Formula weight is based on dihydrate form2Contains 2.4 mg hydrochloric acid 6M

[0204] Ublituximab drug product for IV administrationis filled in Type I, colorless glass vials with siliconized chlorobutyl rubber stoppers that contain a barrier film and sealed with aluminum caps with a plastic button.Attorney Docket No.50581-0016WO1

[0205] Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

Attorney Docket No.50581-0016WO1 WHAT IS CLAIMED IS:

1. A method of treating an autoimmune disease in a human subject, the method comprising, a) subcutaneously administering to the human subject on day 1, a first dose comprising about 50 mg, about 100 mg, about 150 mg, about 225 mg, about 300 mg, or about 400 mg of a population of anti-CD20 antibody proteins, b) intravenously administering to the human subject at about 2 weeks after the first dose, a second dose comprising about 450 mg of the population of anti-CD20 antibody proteins, c) intravenously administering to the human subject at about 6 months after the first dose, a third dose comprising about 450 mg of the population of anti-CD20 antibody proteins, and d) intravenously administering to the human subject at about 6 months after the prior dose, one or more subsequent doses comprising about 450 mg of the population of anti-CD20 antibody proteins; wherein the anti-CD20 antibody proteins in the population comprise: a) a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2; or b) a heavy chain variable region (VH) comprising a VH complementarity determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO:3, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:5; and a light chain variable region (VL) comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:8, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:9, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:10; and wherein the population of anti-CD20 antibody proteins has an N-glycan profile comprising 10 to 20% galactosylated glycans and about 20 to 40% fucosylated glycans.

2. A method of treating an autoimmune disease in a human subject, the method comprising: a) subcutaneously administering to the human subject on day 1, a first dose comprising a population of anti-CD20 antibody proteins in an amount bioequivalent to about 150 mg of the population of anti-CD20 antibody proteins administered intravenously,Attorney Docket No.50581-0016WO1 b) subcutaneously administering to the human subject at about 2 weeks after the first dose, a second dose comprising the population of anti-CD20 antibody proteins in an amount bioequivalent to about 225 mg of the population of anti-CD20 antibody proteins administered intravenously, c) subcutaneously administering to the human subject at about 12 weeks after the first dose, a third dose comprising the population of anti-CD20 antibody proteins in an amount bioequivalent to about 225 mg of the population of anti-CD20 antibody proteins administered intravenously, and d) subcutaneously administering to the human subject at about 12 weeks after the prior dose, one or more subsequent doses comprising the population of anti-CD20 antibody proteins in an amount bioequivalent to about 225 mg of the population of anti-CD20 antibody proteins administered intravenously; wherein the anti-CD20 antibody proteins in the population comprise: a) a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2; or b) a heavy chain variable region (VH) comprising a VH complementarity determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO:3, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:5; and a light chain variable region (VL) comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:8, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:9, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:10; and wherein the population of anti-CD20 antibody proteins has an N-glycan profile comprising 10 to 20% galactosylated glycans and about 20 to 40% fucosylated glycans.

3. A method of treating an autoimmune disease in a human subject, the method comprising: a) subcutaneously administering to the human subject on day 1, a first dose comprising a population of anti-CD20 antibody proteins in an amount bioequivalent to about 150 mg of the population of anti-CD20 antibody proteins administered intravenously, b) subcutaneously administering to the human subject at about 2 weeks after the first dose, a second dose comprising the population of anti-CD20 antibody proteins in an amountAttorney Docket No.50581-0016WO1 bioequivalent to about 150 mg of the population of anti-CD20 antibody proteins administered intravenously, c) subcutaneously administering to the human subject at about 8 weeks after the first dose, a third dose comprising the population of anti-CD20 antibody proteins in an amount bioequivalent to about 150 mg of the population of anti-CD20 antibody proteins administered intravenously, and d) subcutaneously administering to the human subject at about 8 weeks after the prior dose, one or more subsequent doses comprising the population of anti-CD20 antibody proteins in an amount bioequivalent to about 150 mg of the population of anti-CD20 antibody proteins administered intravenously; wherein the anti-CD20 antibody proteins in the population comprise: a) a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2; or b) a heavy chain variable region (VH) comprising a VH complementarity determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO:3, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:5; and a light chain variable region (VL) comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:8, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:9, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:10; and wherein the population of anti-CD20 antibody proteins has an N-glycan profile comprising 10 to 20% galactosylated glycans and about 20 to 40% fucosylated glycans.

4. The method of any one of claims 1-3, wherein the autoimmune disease is multiple sclerosis (MS).

5. The method of claim 4, wherein the MS is a relapsing form of MS (RMS), optionally wherein the RMS is selected from clinically isolated syndrome (CIS), relapsing- remitting MS (RRMS) and active secondary progressive MS SPMS).

6. The method of claim 4 or 5, wherein the subject has an Expanded Disability Status Scale (EDSS) score of from 0 to 5.5 prior to treatment.Attorney Docket No.50581-0016WO1 7. The method of claim 5 or 6, wherein the subject is diagnosed with RMS in accordance to 2017 Revised McDonald Criteria.

8. The method of any one of claims 1-3, wherein the autoimmune disease is rheumatoid arthritis (RA).

9. The method of any one of claims 1-3, wherein the autoimmune disease is lupus.

10. The method of any one of claims 1-3, wherein the autoimmune disease is myasthenia gravis (MG) or chronic inflammatory demyelinating polyneuropathy (CIDP).

11. The method of any one of claims 1 and 4-10, wherein the first dose comprises about 50 mg of the population of anti-CD20 antibody proteins.

12. The method of any one of claims 1 and 4-10, wherein the first dose comprises about 100 mg of the population of anti-CD20 antibody proteins.

13. The method of any one of claims 1 and 4-10, wherein the first dose comprises about 150 mg of the anti-CD20 antibody proteins.

14. The method of any one of claims 1 and 4-10, wherein the first dose comprises about 225 mg of the anti-CD20 antibody proteins.

15. The method of any one of claims 1 and 4-10, wherein the first dose comprises about 300 mg of the anti-CD20 antibody proteins.

16. The method of any one of claims 1 and 4-10, wherein the first dose comprises about 400 mg of the anti-CD20 antibody proteins.Attorney Docket No.50581-0016WO1 17. The method of any one of claims 1 and 4-16, wherein the first dose is administered from a single use vial or a pre-filled syringe that comprises a pharmaceutical formulation comprising about 150 mg / ml of the anti-CD20 antibody proteins.

18. The method of any one of claims 1 and 4-17, wherein the first dose is split over multiple administrations.

19. The method of claim 18, wherein the multiple administrations occur at multiple sites on the human subject’s body.

20. The method of any one of claims 1 and 4-19, wherein the first dose is administered to the subject by a healthcare professional or is self-administered by the subject.

21. The method of any one of claims 1 and 4-20, wherein each of the second dose, the third dose, and the one or more subsequent doses is administered from a single use vial that comprises a pharmaceutical formulation comprising about 50 mg / ml to 150 mg / ml of the anti- CD20 antibody proteins.

22. The method of any one of claims 1 and 4-21, wherein each of the second dose, the third dose, and the one or more subsequent doses is administered by intravenous infusion over 1 hour.

23. The method of claim 2 or 3, wherein the first dose comprises about 265 mg – 450 mg of the population of anti-CD20 antibody proteins, optionally wherein the first dose comprises about 400 mg of the population of anti-CD20 antibody proteins.

24. The method of claim 2 or 3, wherein each of the second dose, the third dose, and the one or more subsequent doses comprises about 265 mg - 450 mg of the population of anti- CD20 antibody proteins, optionally wherein each of the second dose, the third dose, and the one or more subsequent doses comprises about 400 mg of the population of anti-CD20 antibody proteins.Attorney Docket No.50581-0016WO1 25. The method of any one of claims 1-24, wherein the subject has been pre- medicated with a dosage of a corticosteroid 30-60 minutes prior to administration of the population of anti-CD20 antibody proteins.

26. The method of claim 25, wherein the dosage of the corticosteroid is about 100 mg methylprednisone or 10-20 mg dexamethasone.

27. The method of any one of claims 1-26, wherein the subject has been pre- medicated with a dosage of an antihistamine 30-60 minutes prior to administration of the population of anti-CD20 antibody proteins.

28. The method of claim 27, wherein the dosage of the antihistamine is about 25 to 50 mg diphenhydramine HCl.

29. The method of any one of claims 1-28, wherein the subject has been pre- medicated with an antipyretic 30-60 minutes prior to administration of the composition comprising a population of anti-CD20 antibody proteins.

30. The method of claim 29, wherein the antipyretic is acetaminophen or an antipyretic bioequivalent thereto.

31. The method of any one of claims 1-30, wherein a pharmaceutical formulation comprising about 50 mg / mL to 150 mg / mL of the population of anti-CD20 antibody proteins is administered to the subject.

32. The method of claim 31, wherein the pharmaceutical formulation comprises about 150 mg / mL of the population of anti-CD20 antibody proteins.

33. The method of claim 31 or 32, wherein the pharmaceutical formulation further comprises one or more of the following: sodium chloride, sodium citrate, polysorbate 80, and hydrochloric acid.Attorney Docket No.50581-0016WO1 34. The method of claim 33, wherein the pharmaceutical formulation comprises 9.0 mg / mL of sodium chloride.

35. The method of claim 33 or 34, wherein the pharmaceutical formulation comprises 7.4 mg / mL of sodium citrate.

36. The method of any one of claims 33-35, wherein the pharmaceutical formulation comprises 0.7 mg / mL of polysorbate 80.

37. The method of any one of claims 33-36, wherein the pharmaceutical formulation comprises 0.4 mg / mL of hydrochloric acid.

38. The method of any one of claims 33-37, wherein the pharmaceutical formulation comprises 25 mM sodium citrate.

39. The method of any one of claims 33-38, wherein the pharmaceutical formulation comprises 154 mM sodium chloride.

40. The method of any one of claims 33-39, wherein the pharmaceutical formulation comprises 0.07% polysorbate 80.

41. The method of any one of claims 33-40, wherein the pharmaceutical formulation has a pH of 6.

5.

42. A single use vial or pre-filled syringe comprising a pharmaceutical formulation comprising about 50 mg / mL to 150 mg / mL of a population of anti-CD20 antibody proteins, wherein the anti-CD20 antibody protein in the population comprises: a) a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2; or b) a heavy chain variable region (VH) comprising a VH complementarity determining regionAttorney Docket No.50581-0016WO1 (CDR)1 comprising the amino acid sequence of SEQ ID NO:3, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:5; and a light chain variable region (VL) comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:8, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:9, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:10; and wherein the population of anti-CD20 antibody proteins has an N-glycan profile comprising 10 to 20% galactosylated glycans and about 20 to 40% fucosylated glycans.

43. The single use vial or pre-filled syringe of claim 42, wherein the single use vial or pre-filled syringe comprises about 150 mg / mL of the population of anti-CD20 antibody proteins.

44. The single use vial or pre-filled syringe of claim 40 or 41, wherein the single use vial or pre-filled syringe comprises the population of anti-CD20 antibody proteins for delivery to a subject in a volume of about 1 mL to about 3.5 mL, preferably about 1 mL to about 2 mL.

45. The single use vial or pre-filled syringe of any one of claims 42-44, wherein the single use vial or pre-filled syringe comprises the population of anti-CD20 antibody proteins in a volume of about 2 mL.

46. The single use vial or pre-filled syringe of any one of claims 42-45, wherein the pharmaceutical formulation further comprises one or more of the following: sodium chloride, sodium citrate, polysorbate 80, and hydrochloric acid.

47. The single use vial or pre-filled syringe of claim 46, wherein the pharmaceutical formulation comprises 9.0 mg / mL of sodium chloride.

48. The single use vial or pre-filled syringe of claim 46 or 47, wherein the pharmaceutical formulation comprises 7.4 mg / mL of sodium citrate.

49. The single use vial or pre-filled syringe of any one of claims 46-48, wherein the pharmaceutical formulation comprises 0.7 mg / mL of polysorbate 80.Attorney Docket No.50581-0016WO1 50. The single use vial or pre-filled syringe of any one of claims 46-49, wherein the pharmaceutical formulation comprises 0.4 mg / mL of hydrochloric acid.

51. The single use vial or pre-filled syringe of any one of claims 46-50, wherein the pharmaceutical formulation comprises 25 mM sodium citrate.

52. The single use vial or pre-filled syringe of any one of claims 46-51, wherein the pharmaceutical formulation comprises 154 mM sodium chloride.

53. The single use vial or pre-filled syringe of any one of claims 46-52, wherein the pharmaceutical formulation comprises 0.07% polysorbate 80.

54. The single use vial or pre-filled syringe of any one of claims 46-53, wherein the pharmaceutical formulation has a pH of 6.

5.

55. The single use vial or pre-filled syringe of any one of claims 42-54, wherein the anti-CD20 antibody proteins of the population are present in a single dosage form.

56. The single use vial or pre-filled syringe of any one of claims 42-55, for use in a method of any of claims 1-30.

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