Compositions and methods of use of antibodies targeting CD20 and CD3

Abstract

Disclosed herein, in on aspect, is a method of treating an immune or inflammatory disease, comprising administering to a subject in need thereof a therapeutically effective amount of an antibody or antigen-binding fragment thereof that binds to CD20 and CD3, thereby treating the immune or inflammatory disease.

Description

WSGR Docket No. 69143-712.601COMPOSITIONS AND METHODS OF USE OF ANTIBODIES TARGETING CD20 AND CD3CROSS REFERENCE

[0001] This application claims the benefit of the U.S. Provisional Application No. 63 / 735,573, filed December 18, 2024, and U. S. Provisional Application No. 63 / 901 ,096, filed October 17, 2025, each of which is incorporated herein by reference in its entirety.SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled 69143-712_601_SL.xml, created on December 9, 2025, which is 17,208 bytes in size. The information in the electronic format of the Sequence Listing is incorporated by reference in its entirety.INCORPORATION BY REFERENCE

[0003] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material.SUMMARY

[0004] Disclosed herein, in on aspect, is a method of treating an immune or inflammatory disease, comprising administering to a subject inneed thereof atherapeutically effective amount of an antibody or antigenbinding fragment thereof that binds to CD20 and CD3, thereby treating the immune or inflammatory disease.

[0005] Disclosed herein, in another aspect, is a method of eliminating, inhibiting, reducing, or depleting an immune cell in a subject, comprising administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof that binds to CD20 and CD3, thereby eliminating, inhibiting, reducing, or depleting the immune cell.

[0006] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a first polypeptide comprising a first heavy chain variable region (VH1) comprising complementarity determining region (CDR1) 1, CDR2, and CDR3, wherein the VH1-CDR1 comprises the amino acid sequence of SEQ ID NO: 1 , the VH1 -CDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the VH1 -CDR3 comprises the amino acid sequence of SEQ ID NO: 3; a second polypeptide comprising a second heavy chain variable region (VH2) comprising CDR1, CDR2, and CDR3, wherein the VH2-CDR1 comprises the amino acid sequence of SEQ ID NO: 4, the VH2-CDR2 comprises the amino acid sequence of SEQ ID NO: 5, and the VH2-CDR3 comprises the amino acid sequence of SEQ ID NO: 6; a third polypeptide comprising a first tight chain variable region (VL1) comprising CDR1, CDR2, and CDR3, wherein the VL1 -CDR1 comprises the amino acid sequence of SEQ ID NO: 7, the VL1-CDR2 comprises the amino acid sequence of SEQ ID NO: 8, and the VL1-CDR3 comprises the amino acid sequence of SEQ ID NO: 9; and a fourth polypeptide comprising a second tight chain variable region (VL2) comprising CDR1, CDR2, and CDR3, wherein the VL2-CDR1 comprises the amino acidWSGR Docket No. 69143-712.601 sequence of SEQ ID NO: 7, the VL2-CDR2 comprises the amino acid sequence of SEQ ID NO: 8, and the VL2- CDR3 comprises the amino acid sequence of SEQ ID NO: 9.

[0007] In some embodiments, the antibody or antigen-binding fragment thereof further comprises a fragment crystaHizable (Fc) region. In some embodiments, the antibody or antigen-binding fragment thereof further comprises a fragment antigen-binding (Fab) region. In some embodiments, the antibody or antigen-binding fragment thereof further comprises two Fab regions. In some embodiments, the first polypeptide associates with the third polypeptide to form a first Fab region and the second polypeptide associates with the fourth polypeptide to form a second Fab region. In some embodiments, the first polypeptide comprises a first heavy chain constant region 3 (CH3) comprising a first amino acid mutation with reference to a wildtype CH3 sequence, wherein: the first amino acid mutation results in a protrusion in the first polypeptide that is positioned in a cavity in the second polypeptide; or the first amino acid mutation results in a cavity in the first polypeptide that is positioned in a protrusion in the second polypeptide. In some embodiments, the first amino acid mutation comprises a substitution of amino acid residue 354 according to EU numbering with a bulky hydrophobic amino acid. In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), phenylalanine (F), or tryptophan (W). In some embodiment^ the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y) . In some embodiments, the first amino acid mutation further comprises a substitution of amino acid residue 366 according to EU numbering with a bulky hydrophobic amino acid. In some embodiments, the first amino acid mutation comprises the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y). In some embodiments, the first heavy chain CH3 comprises a lysine (K) at amino acid residue 360 according to EU numbering. In some embodiments, the second polypeptide comprises a second heavy chain CH3 comprising a second amino acid mutation with reference to a wildtype 013 sequence, wherein: the second amino acid mutation results in a protrusion in the second polypeptide that is positioned in a cavity in the first polypeptide; or the second amino acid mutation results in a cavity in the second polypeptide that is positioned in a protrusion in the first polypeptide. In some embodiments, the second amino acid mutation comprises a substitution of amino acid residue 347 according to EU numbering with an amino add of negative charge. In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E) or aspartic acid (D). In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E). In some embodiments, the second amino acid mutation further comprises a substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T). In some embodiments, the VH1 or VH2 comprises at least one amino acid mutation that alters an isoelectric point of the antibody or antigen-binding fragment thereof. In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO: 16 and an amino acid substitution of threonine (T) at amino acid residue 83 of SEQ ID NO: 16 according to the Kabat numbering scheme with arginine (R). In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 and an amino acid substitution of glutamine (Q) at each of amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17 according to the Kabat numbering schemeWSGR Docket No. 69143-712.601 with glutamic acid (E). In some embodiments, the first heavy chain CH3 comprises the first amino acid mutation and a lysine (K) at amino acid residue 360 according to EU numbering, wherein the first amino acid mutation comprises: the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y); and the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y); and the second heavy chain CH3 comprises the second amino acid mutation comprising: the substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E); and the substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T).

[0008] In some embodiments, the VH1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ IDNO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino add sequence with at least 95% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ IDNO: 12. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10; the VH2 comprises the amino acid sequence of SEQ ID NO: 11; the VL1 comprises the amino acid sequence of SEQ ID NO: 12; or the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10; the VH2 comprises the amino acid sequence of SEQ ID NO: 11; the VL1 comprises the amino acid sequence of SEQ ID NO: 12; and the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 13; the second polypeptide comprisesWSGR Docket No. 69143-712.601 an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO: 13; the second polypeptide comprises the amino acid sequence of SEQ ID NO: 14; the third polypeptide comprises the amino acid sequence of SEQ ID NO: 15; or the fourth polypeptide comprises the amino acid sequence of SEQ ID NO: 15. In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO: 13; the second polypeptide comprises the amino acid sequence of SEQ ID NO: 14; the third polypeptide comprises the amino acid sequence of SEQ ID NO: 15; and the fourth polypeptide comprises the amino acid sequence of SEQ ID NO: 15.

[0009] In some embodiments, the immune or inflammatory disease is mediated by a B cell, a plasmablast, or a plasma cell. In some embodiments, the immune or inflammatory disease is mediated by a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the immune or inflammatory disease is mediated by an autoantibody. In some embodiments, the immune or inflammatory disease comprises an autoimmune disease.

[0010] In some embodiments, the immune or inflammatory disease comprises allergy, antibody-mediated rejection, alloantibodies, a disease related to or mediated by an alloantibody, amyloidosis, anti -glomerular basement membrane (GBM) (Goodpasture Syndrome), anti-N-methyl-D-aspartate receptor (NMD A) encephalitis (anti-NMDA-R Encephalitis), anti -neutrophil cytoplasmic autoantibody-associated vasculitis (ANCA vasculitis), antiphospholipid antibody syndrome, antisynthetase Syndrome, atopic dermatitis, autoimmune hepatitis, autoimmune necrotizing myopathy, Behcet’s disease, Bullous Pemphigoid, Celiac disease; Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), connective tissue disease- associated interstitial lung disease (CTD-ILD), Crohn’s disease, dilated cardiomyopathy, Graves, Guillain Barre Syndrome, Hi dradenitis Suppurativa, idiopathic pulmonary fibrosis (IPF), IgA Nephropathy, Immunoglobulin G4 -related disease (IgG4-RD), immune vasculitis (IgA), immune thrombocytopenia (ITP), interstitial lung disease (ILD),WSGR Docket No. 69143-712.601Long COVID, Lupus Nephritis, Membranous Nephropathy, microscopic polyangiitis, multiple sclerosis (MS) - primary progressive multiple sclerosis (MS-PPMS), multiple sclerosis (MS) -relapsing-remitting multiple sclerosis (MS-RRMS), myasthenia gravis (MG), myositis-dermatomyositis, myositis-inclusion body, myositispolymyositis, myositis- immune-mediated necrotizing myositis, neuromyelitis optica spectrum disorder (NMOSD), Pemphigus Vulgaris, polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome, Postural Orthostatic Tachycardia Syndrome (POTS), Polyarteritis Nodosa, Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis, Psoriasis, Psoriatic Arthritis, Raynaud’s Syndrome, Reactive Arthritis , rheumatoid arthritis, scleroderma or systemic sclerosis, Sjogren’s Syndrome, Stiff Person Syndrome, Systemic lupus, Systemic lupus erythematosus (SLE), lupus, Type 1 diabetes, Thyroid eye disease, tumor progression, or ulcerative colitis. In some embodiments, the immune or inflammatory disease comprises allergic rhinitis or hay fever, allergic rhinoconjunctivitis, allergic asthma, food allergy, drug allergy, insect sting allergy, urticaria, anaphylaxis, allergic bronchopulmonary aspergillosis (ABPA), allergic fungal sinusitis, atopic dermatitis or eczema, eosinophilic esophagitis, or eosinophilic gastroenteritis. In some embodiments, the immune or inflammatory disease comprises peanut allergy, shellfish allergy, milk allergy, egg allergy, IgE type drug allergy, bee sting allergy, wasp sting allergy, fire ant venom allergy, chronic spontaneous urticaria, or chronic inducible urticaria. In some embodiments, the immune or inflammatory disease comprises penicillin anaphylaxis. In some embodiments, the immune or inflammatory disease is mediated by rheumatoid factor (RF) or anti-citrullinated protein antibodies (ACPA). In some embodiments, the immune or inflammatory disease comprises rheumatoid arthritis. In some embodiments, the immune or inflammatory disease comprises seropositive rheumatoid arthritis. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE). In some embodiments, the immune or inflammatory disease comprises seropositive systemic lupus erythematosus. In some embodiments, the immune or inflammatory disease comprises refractory seropositive systemic lupus erythematosus. In some embodiments, the immune cell comprises a B cell, a plasmablast, or a plasma cell. In some embodiments, the immune cell comprises a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the administering results in a reduction, elimination, inhibition, or depletion of an immune cell or autoantibody. In some embodiments, the administering results in a reduction, elimination, inhibition, or depletion of an immune cell or autoantibody in serum. In some embodiments, the administering results in a rapid and persistent reduction, elimination, inhibition, or depletion of an immune cell or autoantibody in serum. In some embodiments, the administering results in a rapid and persistent reduction, elimination, inhibition, or depletion of an immune cell or autoantibody in serum. In some embodiments, the eliminating, inhibiting, reducing, or depleting the immune cell comprises resulting in a reduction of the immune cell by about 20% to about 100%. In some embodiments, the eliminating, inhibiting, reducing, or depleting the immune cell comprises resulting in a reduction of an autoantibody by about 20% to about 100%. In some embodiments, the eliminating, inhibiting, reducing, or depleting the immune cell comprises resulting in a reduction of the immune cell by about 20% to about 100% in blood or bone marrow. In some embodiments, the administering results in an increase in the expression of an activation biomarker in T cells. In some embodiments, the activation biomarker comprises CD69. In some embodiments, the administering results in the increase in the expression of CD69 in CD4 T cells or CD8WSGR Docket No. 69143-712.601T cells. In some embodiments, the administering results in an increase of a cytokine. In some embodiments, the cytokine comprises interferon gamma (IFN-y). In some embodiments, the administering results in the reduction, elimination, inhibition, or depletion of the immune cell or autoantibody, the increase in the expression of the activation biomarker in T cells, and an increase of the cytokine. In some embodiments, the antibody or antigen - binding fragment thereof has an half-maximal effective concentration (EC50) for the reduction, elimination, inhibition, or depletion of the immune cell or autoantibody, the increase in the expression of the activation biomarker in T cells, or the increase of the cytokine, wherein the EC50 value of the subject is the same as or similar to the EC50 value of a healthy individual. In some embodiments, the ECso value of the subject with rheumatoid arthritis or systemic lupus erythematosus (SLE) is the same as or similar to the ECso value of the healthy individual. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of: tissue B cells, autoantibodies, immunoglobulins, and / or tissue immune deposits. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of: B cells in spleen; double-stranded DNA (dsDNA) in serum; total immunoglobulin G (IgG) in serum; and / or IgG deposits in kidney. In some embodiments, the administering results in a 90% reduction of dsDNA in serum. In some embodiments, the reduction, elimination, inhibition, or depletion starts within 7 days after the administering. In some embodiments, the reduction, elimination, inhibition, or depletion lasts for at least 14 days after the administering.

[0011] In some embodiments, the immune cell comprises a B cell, a plasmablast, or a plasma cell. In some embodiments, the immune cell comprises a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the method comprises administering to the subject a pharmaceutical composition comprising the antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises a buffer, a stabilizing agent, or a surfactant. In some embodiments, the buffer is in an amount of about 3 mg / ml to about 4 mg / ml. In some embodiments, the stabilizing agent is in an amount of about 25 mg / ml to about 35 mg / ml. In some embodiments, the surfactant is in an amount of about 0. 1 mg / ml to about 0.3 mg / ml. In some embodiments, the buffer comprises L-histidine or L-histidine monohydrochloride; the stabilizing agent comprises arginine hydrochloride or methionine; or the surfactant comprises a polysorbate. In some embodiments, the buffer comprises L-histidine and L-histidine monohydrochloride; the stabilizing agent comprises arginine hydrochloride and methionine; and the surfactant comprises a polysorbate. In some embodiments, the polysorbate comprises polysorbate 20 or polysorbate 80. In some embodiments, the buffer is in an amount of about 3.5 mg / ml to about 3.6 mg / ml; the stabilizing agent is in an amount of about 31 mg / ml; and the surfactant is in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition comprises: L-histidine in an amount of about 1.9 mg / ml to about 1.95 mg / ml and L-histidine monohydrochloride in an amount of about 1.6 mg / ml to about 1.65 mg / ml; arginine hydrochloride in an amount of about 29 mg / ml to about 30 mg / ml and methionine in an amount of about 1.5 mg / ml; and polysorbate 20 in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition comprises about 20 mg / ml of the antibody or antigen -binding fragment thereof.WSGR Docket No. 69143-712.601

[0012] In some embodiments, the administering comprises administering a first dose of the antibody or antigen-binding fragment thereof. In some embodiments, the method further comprises administering to the subject a target dose of the antibody or antigen-binding fragment thereof, wherein the target dose is administered after the first dose, wherein the target dose is the same as or higher than the first dose. In some embodiment^ the method further comprises administering to the subject a second dose of the antibody or antigen-binding fragment thereof, wherein the second dose is administered between the first dose and the target dose, wherein the second dose is the same as or higher than the first dose and the target dose is the same as or higher than the second dose. In some embodiments, the method further comprises administering to the subject a third dose of the antibody or antigen-binding fragment thereof, wherein the third dose is administered between the second dose and the target dose, wherein the third dose is the same as or higher than the second dose and the target dose is the same as or higher than the third dose. In some embodiments, the method further comprises administering to the subject a fourth dose of the antibody or antigen -binding fragment thereof, wherein the fourth dose is administered betweai the third dose and the target dose, wherein the fourth dose is the same as or higher than the third dose and the target dose is the same as or higher than the fourth dose. In some embodiments, the first, second, third, fourth, or target dose comprises about 1 mg to about 100 mg of the antibody or antigen-binding fragment thereof. In some embodiments, the first dose comprises about 1 mg to about 3 mg of the antibody or antigen-binding fragment thereof. In some embodiments, the second dose comprises about 3 mg to about 10 mg of the anti both' or antigenbinding fragment thereof. In some embodiments, the third, fourth, or target dose is about 3 mg to about 100 mg of the antibody or antigen-binding fragment thereof. In some embodiments, the first dose is about 1 mg. In some embodiments, the first dose is about 2 mg. In some embodiments, the first dose is about 3 mg. In some embodiments, the second dose is about 3 mg. In some embodiments, the second dose is about 4 mg. In some embodiments, the second dose is about 5 mg. In some embodiments, the second dose is about 6 mg. In some embodiments, the second dose is about 7 mg. In some embodiments, the second dose is about 8 mg. In some embodiments, the second dose is about 9 mg. In some embodiments, the second dose is about 10 mg. In some embodiments, the third, fourth, or target dose is about 3 mg. In some embodiments, the third, fourth, or target dose is about 4 mg. In some embodiments, the third, fourth, or target dose is about 5 mg. In some embodiment^ the third, fourth, or target dose is about 6 mg. In some embodiments, the third, fourth, or target dose is about 7 mg. In some embodiments, the third, fourth, or target dose is about 8 mg. In some embodiments, the third, fourth, or target dose is about 9 mg. In some embodiments, the third, fourth, or target dose is about 10 mg. In some embodiments, the third, fourth, or target dose is about 20 mg. In some embodiments, the third, fourth, or target dose is about 30 mg. In some embodiments, the third, fourth, or target dose is about 40 mg. In some embodiment^ the third, fourth, or target dose is about 50 mg. In some embodiments, the third, fourth, or target dose is about 60 mg. In some embodiments, the third, fourth, or target dose is about 70 mg. In some embodiments, the third, fourth, or target dose is about 80 mg. In some embodiments, the third, fourth, or target dose is about 90 mg. In some embodiments, the third, fourth, or target dose is about 100 mg. In some embodiments, the first dose and the target dose are about 1 mg and about 3 mg, respectively. In some embodiments, the first dose and the target dose are about 3 mg and about 10 mg, respectively. In some embodiments, the first dose, the second dose, and the targetWSGR Docket No. 69143-712.601 dose are about 3 mg, about 10 mg, and about 10 mg, respectively. In some embodiments, the first dose, the second dose, and the target dose are about 3 mg, about 10 mg, and about 30 mg, respectively. In some embodiments, the first dose, the second dose, and the target dose are about 3 mg, about 10 mg, and about 60 mg, respectively. In some embodiments, the first dose, the second dose, and the target dose are about 3 mg, about 10 mg, and about 100 mg, respectively. In some embodiments, two doses of the antibody or antigen-binding fragment thereof are administered at least 7 days apart. In some embodiments, the antibody or antigen-binding fragment thereof is administered on a weekly basis. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 10 days. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 2 weeks. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 3 weeks. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 4 weeks. In some embodiments, the antibody or antigen-binding fragment thereof is administered at most 5 times in 29 days. In some embodiments, the first dose is about 1 mg and the target dose is about 3 mg, wherein the first dose and the target dose are administered on day 1 and day 8, respectively. In some embodiments, the first dose is about 3 mg and the target dose is about 10 mg, wherein the first dose and the target dose are administered on day 1 and day 8, respectively. In some embodiments, the first dose is about 3 mg, the second dose is about 10 mg and the target dose is about 10 mg, wherein the first dose, the second dose and the target dose are administered on day 1, day 8, and day 15, respectively. In some embodiments, the first dose is about 3 mg, the second dose is about 10 mg and the target dose is about 30 mg, wherein the first dose, the second dose and the target dose are administered on day 1, day 8, and day 15, respectively. In some embodiments, the first dose is about 3 mg, the second dose is about 10 mg and the target dose is about 60 mg, wherein the first dose, the second dose and the target dose are administered on day 1, day 8, and day 15, respectively. In some embodiments, the first dose is about 3 mg, the second dose is about 10 mg and the target dose is about 100 mg, wherein the first dose, the second dose and the target dose are administered on day 1, day 8, and day 15, respectively. In some embodiments, the target dose is administered at least twice, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, or at least 10 times. In some embodiments, the target dose is administered once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once in more than 4 weeks. In some embodiments, a dose of the antibody or antigen-binding fragment thereof is administered on day 22 or day 29. In some embodiments, the target dose is administered on day 22 or day 29. In some embodiments, the method further comprises a treatment cycle comprising at least 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, or at least 6 weeks.

[0013] In some embodiments, the therapeutically effective amount of the antibody or antigen -binding fragment thereof is calculated based on a biomarker. In some embodiments, the biomarker comprises a B cell, a plasmablast, a plasma cell, rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), an autoantibody, or an immunoglobulin (Ig). In some embodiments, the biomarker comprises a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the biomarker comprises a free kappa light chain or a free lambda light chain. In some embodiments, the immunoglobulin comprises IgG, IgA, or IgM. In some embodiments, the therapeutically effective amount is calculated based on an amount of the biomarker. In some embodiments, the therapeutically effective amount is calculated based on an amount of the biomarker in blood or bone marrow. InWSGR Docket No. 69143-712.601 some embodiments, the therapeutically effective amount is calculated based on a reduction in the amount of the biomarker in the blood or bone marrow after the administering. In some embodiments, the therapeutically effective amount results in a reduction of about 20% to about 100% of the biomarker after the administering. In some embodiments, the antibody or antigen-binding fragment thereof is administered intramuscularly, intravenously, or subcutaneously. In some embodiments, the antibody or antigen-binding fragment thereof is administered intravenously or subcutaneously. In some embodiments, the subject is treated with a therapy for an adverse effect before, during, or after the administering. In some embodiments, the therapy comprises a corticosteroid, an antihistamine, or an antipyretic. In some embodiments, the therapy comprises dexamethasone; methylprednisolone, diphenhydramine or an equivalent thereof, or acetaminophen or paracetamol or an equivalent thereof. In some embodiments, the therapy comprises about 20 mg of dexamethasone, about 80 mg of methylprednisolone, about 50 mg of diphenhydramine or an equivalent thereof, or about 650 mg to about 1 g of acetaminophen or paracetamol or an equivalent thereof. In some embodiments, the subject is treated with the corticosteroid through intravenous administration at least 1 hour prior to the administering of the antibody or antigen-binding fragment thereof; the antihistamine through intravenous or intramuscular administration at least 30 min prior to the administering of the antibody or antigen-binding fragment thereof; the antihistamine through oral administration at least 1 h prior to the administering of the antibody or antigen-binding fragment thereof; or the antipyretic through oral administration at least 30 min prior to the administering of the antibody or antigenbinding fragment thereof. In some embodiments, the administering results in elimination or reduction of a B cell through antibody-dependent cellular cytotoxicity (ADCC). In some embodiments, the administering results in elimination of a B cell expressing CD20 through antibody-dependent cellular cytotoxicity (ADCC). In some embodiments, the administering results in a reduction of about 20% to about 100% of a B cell. In some embodiments, the administering results in a reduction of about 20% to about 100% of an autoantibody. In some embodiments, the administering results in a reduction of about 20% to about 100% of a B cell in blood or bone marrow. In some embodiments, the administering results in a reduction of at least 20% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of at least 30% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of at least 40% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of at least 50% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of at least 60% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of at least 70% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of at least 80% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of at least 90% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of about 100% of a B cell or an autoantibody. In some embodiments, the method further comprises revaccinating the subject. In some embodiments, the administering does not result in a significant effect on a T cell.

[0014] In some embodiments, the subject is treated with a therapy for neutropenia, anaemia, leukopenia, COVID-19 infection, hypokalemia, cytokine release syndrome, infection, thrombocytopenia, or an infusion- related reaction, before, during, or after the administering. In some embodiments, the subject is diagnosed withWSGR Docket No. 69143-712.601 adult-onset rheumatoid arthritis based on the 2010 American College of Rheumatology (ACR) or European League Against Rheumatism (EULAR) classification criteriaat least 3 months prior to the administering. In some embodiments, the subject is refractory to a prior treatment before the administering, wherein the prior treatment comprises a biologic disease- modifying antirheumatic drug (bDMARD) or atargeted synthetic disease-modifying antirheumatic drug (tsDMARD), wherein the subject exhibits inadequate treatment response, lack of clinical benefit, or poor tolerability after at least 12 weeks of the prior treatment. In some embodiments, the prior treatment comprises 2 bDMARDs in different mechanism classes, or 1 bDMARD and 1 tsDMARD. In some embodiments, the prior treatment comprises a tumor necrosis factor (TNF) inhibitor. In some embodiments, the subject exhibits no intolerance to a prior B cell depletion therapy. In some embodiments, the subject exhibits moderate to severe active rheumatoid arthritis. In some embodiments, the subject has at least 6 / 68 tender joints and at least 6 / 66 swollen joints. In some embodiments, the subject tests positive for rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA). In some embodiments, the subject, prior to or during the administering, is treated with methotrexate (MTX), hydroxychloroquine, leflunomide, oral sulfasalazine, azathioprine, my cophenol ate, oral prednisone, anon-steroidal anti-inflammatory drug, folic acid, or folinic acid. In some embodiments, the subject is not treated with a parenteral corticosteroid prior to the administering. In some embodiments, the subject has: detectable peripheral B cells in an amount of at least 25 cells / ml; absolute neutrophil count of at least 2.0 x 109 / L; platelet count of at least 100 / 109 / L; hemoglobinlevel ofat least lO.Og / dL; a lymphocyte count of more than 500 cells / pL; a total leukocyte count of at least 3.0 x 109 / L; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of at least 2 times of the upper limit of normal (ULN); and total bilirubin and alkaline phosphatase levels less than 1.5 time of the ULN, wherein the subject has serum direct bilirubin less than 1.5 mg / dL when the subject has Gilbert’s syndrome. In some embodiments, the subject does not have a class IV rheumatoid arthritis according to American College of Rheumatology (ACR) revised response criteria; the subj ect does not have a history of a rheumatologic autoimmune disease other than rheumatoid arthritis; the subj ect does not have secondary Sjogren’s syndrome; the subject does not have a significant systemic involvement secondary to rheumatoid arthritis; the subject does not have Felty’s syndrome; the subject does not have juvenile idiopathic arthritis or idiopathic arthritis diagnosed before the age of 16 years; the subject does not have psoriatic arthritis; the subject does not have axial spondylarthritis or any other disease associated with inflammatory arthritis; the subject does not have aprior rheumatoid arthritis treatment comprising: an anti -CD 19 therapy or an anti-CD20 therapy, optionally comprising blinatumomab, obinutuzumab, rituximab, ocrelizumab, or ofatumumab, less than 6 months prior to the administering; a cell depleting therapy, optionally comprising an anti-CD4 therapy, anti-CD5 therapy, or an anti-CD3 therapy, less than 6 months prior to the administering; a JAK inhibitor, a Bruton tyrosine kinase (BTK) inhibitor, or a tyrosine kinase 2 (TYK2) inhibitor, optionally comprising baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, fenebrutinib, deucravacitinib, brepocitinib, ropsacitinib, within 4 weeks prior to the administering; an immunomodulatory bDMARD, optionally comprising adalimumab, golimumab, ustekinumab, secukinumab, tocilizumab, abatacept, etanercept, anakinra, infliximab, certolizumab pegol, IL-6, IL-23, or IL-17, less than 12 weeks or 5 half-lives, prior to the administering; an experimental CAR-T or TCE therapy less than 12 months prior to the administering; a calcineurin inhibitor lessWSGR Docket No. 69143-712.601 than 8 weeks prior to the administering; or a cyclophosphamide less than 24 weeks prior to the administering; the subject is not intolerant to a B cell depleting therapy; the subject does not have progressive multifocal leukoencephalopathy; and the subject does not have stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. In some embodiments, the antibody or antigen-binding fragment thereof binds to a first target and a second target. In some embodiments, the first target comprises CD20 and the second target comprises CD3.

[0015] Disclosed herein, in another aspect, is a method of treating an immune or inflammatory disease, comprising: administering to a subject in need thereof a first dose of an antibody or antigen-binding fragment thereof that binds to CD20 and CD3; and measuring a biomarker in the subject.

[0016] In some embodiments, the immune or inflammatory disease comprises allergy, antibody-mediated rejection, alloantibodies, a disease related to or mediated by an alloantibody, amyloidosis, anti -glomerular basement membrane (GBM) (Goodpasture Syndrome), anti-N-methyl-D-aspartate receptor (NMD A) encephalitis (anti-NMDA-R Encephalitis), anti -neutrophil cytoplasmic autoantibody-associated vasculitis (ANCA vasculitis), antiphospholipid antibody syndrome, antisynthetase Syndrome, atopic dermatitis, autoimmune hepatitis, autoimmune necrotizing myopathy, Behcet’s disease, Bullous Pemphigoid, Celiac disease; Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), connective tissue disease- associated interstitial lung disease (CTD-ILD), Crohn’s disease, dilated cardiomyopathy, Graves, Guillain Barre Syndrome; Hidradenitis Suppurativa, idiopathic pulmonary fibrosis (IPF), IgA Nephropathy, Immunoglobulin G4-related disease (IgG4-RD), immune vasculitis (IgA), immune thrombocytopenia (ITP), interstitial lung disease (ILD), Long COVID, Lupus Nephritis, Membranous Nephropathy, microscopic polyangiitis, multiple sclerosis (MS) - primary progressive multiple sclerosis (MS-PPMS), multiple sclerosis (MS) -relapsing-remitting multiple sclerosis (MS-RRMS), myasthenia gravis (MG), myositis-dermatomyositis, myositis-inclusion body, myositispolymyositis, myositis- immune-mediated necrotizing myositis, neuromyelitis optica spectrum disorder (NMOSD), Pemphigus Vulgaris, polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome, Postural Orthostatic Tachycardia Syndrome (POTS), Polyarteritis Nodosa, Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis, Psoriasis, Psoriatic Arthritis, Raynaud’s Syndrome, Reactive Arthritis , rheumatoid arthritis, scleroderma or systemic sclerosis, Sjogren’s Syndrome, Stiff Person Syndrome, Systemic lupus, Systemic lupus erythematosus (SLE), lupus, Type 1 diabetes, Thyroid eye disease, tumor progression, or ulcerative colitis. In some embodiments, the immune or inflammatory disease comprises allergic rhinitis or hay fever, allergic rhinoconjunctivitis, allergic asthma, food allergy, drug allergy, insect sting allergy, urticaria, anaphylaxis, allergic bronchopulmonary aspergillosis (ABPA), allergic fungal sinusitis, atopic dermatitis or eczema, eosinophilic esophagitis, or eosinophilic gastroenteritis. In some embodiments, the immune or inflammatory disease comprises peanut allergy, shellfish allergy, milk allergy, egg allergy, IgE type drug allergy, bee sting allergy, wasp sting allergy, fire ant venom allergy, chronic spontaneous urticaria, or chronic inducible urticaria. In some embodiments, the immune or inflammatory disease comprises penicillin anaphylaxis.

[0017] In some embodiments, the biomarker comprises a B cell, a plasmablast, a plasma cell, rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), an autoantibody, or an immunoglobulin (Ig). In some embodiments, the biomarker comprises a mature B cell, a memory B cell, or an activated B cell. In someWSGR Docket No. 69143-712.601 embodiments, the biomarker comprises a free kappa light chain or a free lambda light chain. In some embodiments, the immunoglobulin comprises IgG, IgA, or IgM. In some embodiments, the immune or inflammatory diseaseis mediated by a B cell, a plasmablast, a plasma cell, an autoantibody, or an immunoglobulin (Ig). In some embodiments, the immune or inflammatory disease is mediated by B-cell activating factor (BAFF). In some embodiments, the immune or inflammatory disease is mediated by a free kappa light chain or a free lambda light chain. In some embodiments, the Ig comprises IgG, IgA, or IgM. In some embodiments, the measuring comprises measuring an amount of the biomarker in blood or bone marrow after the administering the first dose. In some embodiments, the method further comprises, after the measuring, comparing the amount of the biomarker to a base level. In some embodiments, the method further comprises, after the comparing, calculating a reduction in an amount of the biomarker. In some embodiments, the reduction in the amount of the biomarker that is equal to or higher than a reference level indicates that the first dose is a therapeutically effective for treating the immune or inflammatory disease. In some embodiments, the reduction in the amount of the biomarker that is lower than the reference level indicates that the first dose is not therapeutically effective for treating the immune or inflammatory disease. In some embodiments, the reference level is about 20% to about 100%. In some embodiments, the reference level is at least about 20%. In some embodiments, the reference level is at least about 30%. In some embodiments, the reference level is at least about 40%. In some embodiment^ the reference level is at least about 50%. In some embodiments, the reference level is at least about 60%. In some embodiments, the reference level is at least about 70%. In some embodiments, the reference level is at least about 80%. In some embodiments, the reference level is at least about 90%. In some embodiments, the reference level is at least about 95%. In some embodiments, the reference level is at least about 99%. In some embodiment^ the reference level is about 100%.

[0018] In some embodiments, the method further comprising administers to the subject a second dose of the antibody or antigen-binding fragment thereof when the first dose is not therapeutically effective for treating the immune or inflammatory disease, wherein the second dose is higher than the first dose. In some embodiment^ the second dose is calculated based on an amount of the biomarker. In some embodiments, the second dose is calculated based on an amount of the biomarker in serum. In some embodiments, the second dose is calculated based on a reduction or an increase in the amount of the biomarker in the serum after the administering. In some embodiments, the measuring comprises measuring an amount of the biomarker in serum after the administering the first dose. In some embodiments, the method further comprises, after the measuring, comparing the amount of the biomarker to a base level. In some embodiments, the method further comprises, after the comparing, calculating a reduction or an increase in an amount of the biomarker. In some embodiments, the reduction or increase in the amount of the biomarker that is equal to or higher than a reference level indicates that the first dose is a therapeutically effective for treating the disease. In some embodiments, the immune or inflammatory disease is mediated by a B cell, a plasmablast, or a plasma cell. In some embodiments, the immune or inflammatory disease is mediated by a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the immune or inflammatory disease is mediated by an autoantibody. In some embodiments, the immune or inflammatory disease comprises an autoimmune disease. In some embodiments, the immune orWSGR Docket No. 69143-712.601 inflammatory disease is mediated by rheumatoid factor (RF) or anti-citrullinated protein antibodies (ACPA). In some embodiments, the immune or inflammatory disease comprises rheumatoid arthritis. In some embodiments, the immune or inflammatory disease comprises seropositive rheumatoid arthritis.

[0019] In some embodiments, the antibody or antigen-binding fragment thereof comprises: a first polypeptide comprising a first heavy chain variable region (VH1) comprising complementarity determining region (CDR1) 1, CDR2, and CDR3, wherein the VH1-CDR1 comprises the amino acid sequence of SEQ ID NO: 1, the VH1-CDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the VH1-CDR3 comprises the amino acid sequence of SEQ ID NO: 3; a second polypeptide comprising a second heavy chain variable region (VH2) comprising CDR1, CDR2, and CDR3, wherein the VH2-CDR1 comprises the amino acid sequence of SEQ ID NO: 4, the VH2-CDR2 comprises the amino acid sequence of SEQ ID NO: 5, and the VH2-CDR3 comprises the amino acid sequence of SEQ ID NO: 6; a third polypeptide comprising a first light chain variable region (VL1) comprising CDR1, CDR2, and CDR3, wherein the VL1 -CDR1 comprises the amino acid sequence of SEQ ID NO: 7, the VL1-CDR2 comprises the amino acid sequence of SEQ ID NO: 8, and the VL1-CDR3 comprises the amino acid sequence of SEQ ID NO: 9; and a fourth polypeptide comprising a second light chain variable region (VL2) comprising CDR1, CDR2, and CDR3, wherein the VL2-CDR1 comprises the amino acid sequence of SEQ ID NO: 7, the VL2-CDR2 comprises the amino acid sequence of SEQ ID NO: 8, and the VL2- CDR3 comprises the amino acid sequence of SEQ ID NO: 9. In some embodiments, the antibody or antigenbinding fragment thereof further comprises a fragment crystahizable (Fc) region. In some embodiments, the antibody or antigen-binding fragment thereof further comprises a fragment antigen-binding (Fab) region. In some embodiments, the antibody or antigen-binding fragment thereof further comprises two Fab regions. In some embodiments, the first polypeptide associates with the third polypeptide to form a first Fab region and the second polypeptide associates with the fourth polypeptide to form a second Fab region. In some embodiments, the first polypeptide comprises a first heavy chain constant region 3 (CH3) comprising a first amino acid mutation with reference to a wildtype CH3 sequence, wherein the first amino acid mutation results in a protrusion in the first polypeptide that is positioned in a cavity in the second polypeptide; or the first amino acid mutation results in a cavity in the first polypeptide that is positioned in a protrusion in the second polypeptide. In some embodiments, the first amino acid mutation comprises a substitution of amino acid residue 354 according to EU numbering with a bulky hydrophobic amino acid. In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), phenylalanine (F), or tryptophan (W). In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y). In some embodiments, the first amino add mutation further comprises a substitution of amino acid residue 366 according to EU numbering with a bully hydrophobic amino acid. In some embodiments, the first amino acid mutation comprises the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y). In some embodiments, the first polypeptide comprises the first heavy chain CH3 comprising a lysine (K) at amino acid residue 360 according to EU numbering. In some embodiments, the second polypeptide comprises a second heavy chain CH3 comprising a second amino acid mutation with reference to a wildtype CH3 sequence, wherein the second aminoWSGR Docket No. 69143-712.601 acid mutation results in a protrusion in the second polypeptide that is positioned in a cavity in the first polypeptide; or the second amino acid mutation results in a cavity in the second polypeptide that is positioned in a protrusion in the first polypeptide. In some embodiments, the second amino acid mutation comprises a substitution of amino acid residue 347 according to EU numbering with an amino acid of negative charge. In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E) or aspartic acid (D). In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E). In some embodiments, the second amino acid mutation further comprises a substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T). In some embodiments, the VH1 or VH2 comprises at least one amino acid mutation that alters an isoelectric point of the antibody or antigen -binding fragment thereof. In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO: 16 and an amino acid substitution of threonine (T) at amino acid residue 83 of SEQ ID NO: 16 according to the Kabat numbering scheme with arginine (R). In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 and an amino acid substitution of glutamine (Q) at each of amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17 according to the Kabat numbering scheme with glutamic acid (E). In some embodiment^ the first heavy chain CH3 comprises the first amino acid mutation and a lysine (K) at amino acid residue 360 according to EU numbering, wherein the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y); and the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y) ; and the second heavy chain CH3 comprises the second amino acid mutation comprising: the substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E); and the substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T).

[0020] In some embodiments, the VH1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ IDNO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino add sequence with at least 95% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 95%WSGR Docket No. 69143-712.601 sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQIDNO: 12. In some embodiments, the VH1 comprises the amino acid sequence ofSEQ ID NO: 10; the VH2 comprises the amino acid sequence of SEQ ID NO: 11; the VL1 comprises the amino acid sequence of SEQ ID NO: 12; or the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10; the VH2 comprises the amino acid sequence of SEQ ID NO: 11; the VL1 comprises the amino acid sequence of SEQ ID NO: 12; and the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO: 13; the second polypeptide comprises the amino acid sequence of SEQ ID NO: 14; the third polypeptide comprises the amino acid sequence of SEQ ID NO: 15; or the fourth polypeptide comprises the amino acid sequence of SEQ ID NO: 15. In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO: 13; the second polypeptide comprises the amino acid sequence of SEQ ID NO: 14; the third polypeptide comprises the amino acid sequence of SEQ ID NO: 15; and the fourth polypeptide comprises the amino acid sequence of SEQ ID NO: 15. In some embodiments, theWSGR Docket No. 69143-712.601 antibody or antigen-binding fragment thereof binds to a first target and a second target. In some embodiment^ the first target comprises CD20 and the second target comprises CD3. In some embodiments, the method further comprises administering a nucleic acid molecule encoding the antibody or antigen-binding fragment thereof In some embodiments, the method further comprises administering a vector comprising the nucleic acid molecule. In some embodiments, the method further comprises administering a cell expressing the antibody or antigenbinding fragment thereof. In some embodiments, the cell comprises the nucleic acid molecule encoding the antibody or antigen-binding fragment thereof. In some embodiments, the cell comprises the vector comprising the nucleic acid sequence. In some embodiments, the nucleic acid molecule comprises DNA or RNA. In some embodiments, the nucleic acid molecule comprises mRNA. In some embodiments, the method further comprises administering a lipid particle comprising the nucleic acid molecule. In some embodiments, the method further comprises administering a lipid nanoparticle comprising the nucleic acid molecule. In some embodiments, the method further comprises administering a lipid nanoparticle comprising mRNA encoding the antibody or antigenbinding fragment thereof.

[0021] Disclosed herein is a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that binds to CD20 and CD3; a buffer in an amount of about 3 mg / ml to about 4 mg / ml; a stabilizing agent in an amount of about 25 mg / ml to about 35 mg / ml; and a surfactant in an amount of about 0.1 mg / ml to about 0.3 mg / ml.

[0022] In some embodiments, the antibody or antigen-binding fragment thereof comprises afirst polypeptide comprising a first heavy chain variable region (VH1) comprising complementarity determining region (CDR1) 1 , CDR2, and CDR3, wherein the VH1 -CDR1 comprises the amino acid sequence of SEQ ID NO: 1 , the VH1 - CDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the VH1 -CDR3 comprises the amino acid sequence of SEQ ID NO: 3; a second polypeptide comprising a second heavy chain variable region (VH2) comprising CDR1, CDR2, and CDR3, wherein the VH2-CDR1 comprises the amino acid sequence of SEQ ID NO: 4, the VH2-CDR2 comprises the amino acid sequence of SEQ ID NO: 5, and the VH2-CDR3 comprises the amino acid sequence of SEQ ID NO: 6; a third polypeptide comprising a first light chain variable region (VL1) comprising CDR1, CDR2, and CDR3, wherein the VL1-CDR1 comprises the amino acid sequence of SEQ ID NO: 7, the VL1-CDR2 comprises the amino acid sequence of SEQ ID NO: 8, and the VL1 -CDR3 comprises the amino acid sequence of SEQ ID NO: 9; and a fourth polypeptide comprising a second light chain variable region (VL2) comprising CDR1, CDR2, and CDR3, wherein the VL2-CDR1 comprises the amino acid sequence of SEQ ID NO: 7, the VL2-CDR2 comprises the amino acid sequence of SEQ ID NO: 8, and the VL2-CDR3 comprises the amino acid sequence of SEQ ID NO: 9. In some embodiments, the antibody or antigen-binding fragment thereof further comprises a fragment crystaHizable (Fc) region. In some embodiments, the antibody or antigenbinding fragment thereof further comprises a fragment antigen-binding (Fab) region. In some embodiments, the antibody or antigen-binding fragment thereof further comprises two Fab regions. In some embodiments, the first polypeptide associates with the third polypeptide to form a first Fab region and the second polypeptide associates with the fourth polypeptide to form a second Fab region. In some embodiments, the first polypeptide comprises a first heavy chain constant region 3 (CH3) comprising a first amino acid mutation with reference to a wildtypeWSGR Docket No. 69143-712.601CH3 sequence, wherein the first amino acid mutation results in a protrusion in the first polypeptide that is positioned in a cavity in the second polypeptide; or the first amino acid mutation results in a cavity in the first polypeptide that is positioned in a protrusion in the second polypeptide. In some embodiments, the first amino acid mutation comprises a substitution of amino acid residue 354 according to EU numbering with a bully hydrophobic amino acid. In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), phenylalanine (F), or tryptophan (W). In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y). In some embodiments, the first amino acid mutation further comprises a substitution of amino acid residue 366 according to EU numbering with a bulky hydrophobic amino acid. In some embodiments, the first amino acid mutation comprises the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y) . In some embodiments, the first polypeptide comprises the first heavy chain CH3 comprising a lysine (K) at amino acid residue 360 according to EU numbering. In some embodiments, the second polypeptide comprises a second heavy chain CH3 comprising a second amino acid mutation with reference to a wildtype CH3 sequence, wherein the second amino acid mutation results in a protrusion in the second polypeptide that is positioned in a cavity in the first polypeptide; or the second amino acid mutation results in a cavity in the second polypeptide that is positioned in a protrusion in the first polypeptide. In some embodiments, the second amino acid mutation comprises a substitution of amino acid residue 347 according to EU numbering with an amino acid of negative charge. In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E) or aspartic acid (D). In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E). In some embodiments, the second amino acid mutation further comprises a substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T). In some embodiments, the VH1 or VH2 comprises at least one amino acid mutation that alters an isoelectric point of the antibody or antigen-binding fragment thereof. In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO: 16 and an amino acid substitution of threonine (T) at amino acid residue 83 of SEQ ID NO: 16 according to the Kabat numbering scheme with arginine (R). In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 and an amino acid substitution of glutamine (Q) at each of amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17 according to the Kabat numbering scheme with glutamic acid (E). In some embodiment^ the first heavy chain CH3 comprises the first amino acid mutation and a lysine (K) at amino acid residue 360 according to EU numbering, wherein the first amino acid mutation comprises: the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y); and the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y) ; and the second heavy chain CH3 comprises the second amino acid mutation comprising: the substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E); and the substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T).WSGR Docket No. 69143-712.601

[0023] In some embodiments, the VH1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12. In some embodiment^ the VH1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino add sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10; the VH2 comprises the amino acid sequence of SEQ ID NO: 11 ; the VL1 comprises the amino acid sequence of SEQ ID NO: 12; or the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10; the VH2 comprises the amino acid sequence of SEQ ID NO: 11; the VL1 comprises the amino acid sequence of SEQ ID NO: 12; and the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 90%WSGR Docket No. 69143-712.601 sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO: 13; the second polypeptide comprises the amino acid sequence of SEQ ID NO: 14; the third polypeptide comprises the amino acid sequence of SEQ ID NO: 15; or the fourth polypeptide comprises the amino acid sequence of SEQ ID NO: 15. In some embodiments, the first polypeptide comprises the amino acid sequence ofSEQID NO: 13; thesecond polypeptide comprises the amino acid sequence of SEQ ID NO: 14; the third polypeptide comprises the amino acid sequence of SEQ ID NO: 15; and the fourth polypeptide comprises the amino acid sequence of SEQ IDNO: 15.

[0024] In some embodiments, the buffer comprises L-histidine or L-histidine monohydrochloride; the stabilizing agent comprises arginine hydrochloride or methionine; or the surfactant comprises a polysorbate. In some embodiments, the buffer comprises L-histidine and L-histidine monohydrochloride; the stabilizing agent comprises arginine hydrochloride and methionine; and the surfactant comprises a polysorbate. In some embodiments, the polysorbate comprises polysorbate 20 or polysorbate 80. In some embodiments, the pharmaceutical composition comprises the buffer in an amount of about 3.5 mg / ml to about 3.6 mg / ml; the stabilizing agent in an amount of about 31 mg / ml; and the surfactant in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition comprises L-histidine in an amount of about 1.9 mg / ml to about 1.95 mg / ml and L-histidine monohydrochloride in an amount of about 1.6 mg / ml to about 1.65 mg / ml; arginine hydrochloride in an amount of about 29 mg / ml to about 30 mg / ml and methionine in an amount of about 1.5 mg / ml; and polysorbate 20 in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition comprises L-histidine in an amount of about 1.92 mg / ml and L-histidine monohydrochloride in an amount of about 1.61 mg / ml; arginine hydrochloride in an amount of about 29.5 mg / ml and methionine in an amount of about 1.5 mg / ml; and polysorbate 20 in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition comprises about 20 mg / ml of the antibody or antigen-binding fragment thereof In some embodiments, the antibody or antigen-binding fragment thereof binds to a first target and a second target. In some embodiments, the first target comprises CD20 and the second target comprises CD3.BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The novel features of the disclosure are set forth with particularity in the appended claims. The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.WSGR Docket No. 69143-712.601A beter understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings (also “Figure” and “FIG.” herein), of which:

[0026] Fig. 1 illustrates an exemplary embodiment of the design and dosing scheme of the clinical study of the antibody PC-1 targeting CD20 and CD3.

[0027] Fig. 2 illustrates boxplot of PC-1 ECso Values for Target B cell depletion, CD69 activation on CD4 T or CD8 T cells, and IFN-y release in HV, RA, and SLE Donors

[0028] Fig. 3 illustrates evaluation of PC- 1 -mediated human splenic CD19+ B-cell depletion in SLE PBMC humanized NOG Mice (Day 21)

[0029] Fig. 4 illustrates flow cytometry of peripheral blood CD19+ B cells in seropositive RA patients treated with PC-1 by dose cohort in study PC- 1-101

[0030] Fig. 5 illustrates flow cytometry of peripheral blood CD 19+ B cells in refractory, seropositive SLE patients treated with PC-1 by dose cohort in study PC- 1-102.DETAILED DESCRIPTION

[0031] In the context of the present application, the following terms have the meanings ascribed to them unless specified otherwise:

[0032] As used throughout the specification and claims, the terms “a”, “an” and “the” are generally used in the sense that they mean “at least one”, “at least a first”, “one or more” or “a plurality” of the referenced components or steps, except in instances wherein an upper limit is thereafter specifically stated. For example, a “cleavage sequence”, as used herein, means “at least a first cleavage sequence” but includes a plurality of cleavage sequences. The operable limits and parameters of combinations, as with the amounts of any single agent, will be known to those of ordinary skill in the art in light of the present application.

[0033] Unless otherwise indicated or defined, the terms “comprise”, “comprises”, and “comprising” and other variants thereof such as “including” and “containing” should be understood to mean including the indicated elements or steps or element groups or step groups, without excluding any other elements or steps or element groups or step groups.

[0034] The terms “polypeptide”, “peptide”, and “protein” are used interchangeably herein to generally refs’ to polymers of amino acids of any length. The polymer may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified, for example, by disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component.

[0035] As used herein, the term “antibody” refers to an immunoglobulin molecule that has the ability to bind specifically to a particular antigen. As used herein, the term “antibody” should be understood in its broadest sense and includes monoclonal or polyclonal antibodies, full-length antibodies, antibody fragments, a portion of an antibody, an antigen-binding fragment, an antigen-binding portion, an antigen-binding domain, , an antigenbindingregion, monospecific antibodies, multispecific antibodies containing at least two antigen-binding region^ and bispecific antibodies containing two antigen-binding regions. The term “antibody” may include differentWSGR Docket No. 69143-712.601 antibody forms, such as fragment antigen-binding (Fab) region, single chain variable fragment (scFv), or single domain antibodies (VHH) or any other antibody form. For example, an antibody may include one or more of heavy chain variable region (VH), light chain variable region (VL), heavy chain constant domain 1 (CHI ), ahinge region, heavy chain constant domain 2 (CH2), heavy chain constant domain 3 (CH3), and fragment crystallizable (Fc) region. Antibodies may contain additional modifications, such as non-naturally occurring amino acids, mutations in the Fc region, and mutations in glycosylation sites. Antibodies also include post-translationally modified antibodies, fusion proteins containing the antigenic determinants of antibodies, and immunoglobulin molecules containing any other modifications to the antigen recognition sites, as long as these antibodies exhibit desired biological activities.

[0036] The “Light Chain Variable Region” (VL) or “Heavy Chain Variable Region” (VH) may include “framework” regions separated by three “Complementarity -Determining Regions” or “CDRs.” CDRs comprise amino acid residues in the antibody that are primarily responsible for antigen binding. Both the VL and VH domains contain the following framework regions (FR) and CDR regions from the amino terminus to the carboxyl terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, andFR4. The amino acid arrangement of each ofthe VL domain and the VH domain is consistent with any conventional definition of CDR. Conventional definitions include the Kabat definition (Kabat, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, MD, 1987 and 1991)), the Chothia definition (Chothia and Lesk, J. Mol. Biol. 196:901-917, 1987; Chothia et al., Nature 342:878-883, 1989); and a composite of the Chothia Kabat CDR, wherein CDR-H1 is a composite of the Chothia CDR and the Kabat CDR; AbM definition used by Oxford Molecular's antibody modeling software; and the CONTACT definition of Martin et al. (e.g., world wide web bioinfo.org.uk / abs) and IMGT definition (e.g., https: / / www.imgt.org / IMGTindex / CDR.php). Kabat provides a widely used numbering convention (Kabat numbering system), wherein the corresponding residues between different heavy chains or between different light chains are assigned the same numberings. The present disclosure may use CDRs defined according to any one of these numbering systems, but preferred embodiments use Kabat-defined CDRs.

[0037] The term “bispecific antibody” may be understood to mean an antibody having two different antigenbinding regions. This can be understood as binding to two different targets, but also includes binding to two different epitopes of one target. The term “bispecific antibody” as used herein should be understood in its broadest sense, including full-length bispecific antibodies and antigen-binding portions or fragments thereof. Bispecific antibodies may contain additional modifications such as non-naturally occurring amino acids, mutations in the Fc region, and mutations in glycosylation sites. Bispecific antibodies also include post-translationally modified antibodies, fusion proteins containing antigenic determinants of antibodies, and immunoglobulin molecules containing any other modifications to the antigen recognition sites, as long as these antibodies exhibit desired biological activities.

[0038] As used herein, the term “antigen-binding fragment,” “a portion” “an antigen-binding domain,” “an antigen- binding portion,” or “an antigen-binding region,” of an antibody refers to one or more fragments of an antibody that retain the ability to specifically bind to the antigen. It has been shown that the antigen-binding function of an antibody can be implemented by a fragment of a full-length antibody. Examples of antigen-bindingWSGR Docket No. 69143-712.601 fragments covered by the term “antigen-binding domain” of an antibody include: (i) Fab fragments, which are monovalent fragments consisting of VL, VH, CL and CHI domains; (ii) F(ab’)2 fragments, which are bivalent fragments comprising two Fab fragments linked by a disulfide bond in the hinge region; (iii) Fab' fragment^ which are essentially Fab having a partial hinge region; (iv) Fd fragments, which consist of VH and CHI domains; (v) Fd' fragments, which have VH and CHI domains and one or more cysteine residues at the C-terminus of the CHI domain; (vi) Fv fragments, which consist of VL and VH domains of a single arm of the antibody; (vii) dAb fragments, which consist of a VH domain; (viii) isolated complementarity -determining regions (CDR); and (ix) nanobodies, heavy chain variable regions comprising a single variable domain and two constant domains. In addition, although the two VL and VH domains of the Fv fragment are encoded by different genes, recombinant methods may be used to connect them via a synthetic linker to enable them to be made into a single protein chain in which the VL and VH regions are paired up to form a monovalent molecule (referred to as single-chain Fv (scFv)). Such single-chain antibodies are also intended to be encompassed within the term “antigen-binding fragment” of an antibody. In addition, the term also includes “straight chain antibodies” comprising a pair of tandem Fd fragments (VH-CH1-VH-CH1), which together with a complementary light chain polypeptide form an antigen- binding region, as well as modified forms of any of the foregoing fragments which retain antigen - binding activities.

[0039] Based on the amino acid sequences of the constant regions of the heavy chains of antibodies, immunoglobulin molecules can be classified into five types (isotypes): IgA, IgD, IgE, IgG, and IgM, and can be further classified into different subtypes, e.g., IgGl, IgG2, IgG3, IgG4, IgAl, and IgA2. Based on the amino add sequences of the light chains, the light chains of antibodies can be categorized into lambda (X) chains and kappa (K) chains.

[0040] These antigen-binding fragments can be obtained by using conventional techniques known to those skilled in the art, and the fragments are screened for efficacy in the same manner as intact antibodies.

[0041] As used herein, the term “binding” or “specifically binding” refers to a non-random binding reaction between two molecules such as an antibody and its target antigen. The binding specificity of an antibody can be determined based on affinity and / or avidity. Affinity represents an equilibrium constant of antigen-antibody dissociation (KD) and is a measure of the strength of binding between an antigenic determinant and an antigen binding site of an antibody: the smaller the value of KD, the stronger the strength of binding between the antigenic determinant and the antibody. Alternatively, affinity can also be represented as an affinity constant (KA), which is 1 / KD.

[0042] As used herein, the term “sequence identity” refers to the extent to which two sequences (amino acids) have the same residue at the same position after alignment. For example, “an amino acid sequence is X% identical with SEQ ID NO: Y” means that the amino acid sequence has an identity of X% with SEQ ID NO: Y and is described as X% of the residues in the amino acid sequence being identical with residues in the sequence disclosed in SEQ ID NO: Y. Typically, a computer program is used to perform such calculations. Exemplary programs for comparing and aligning sequence pairs include ALIGN, FASTA, gapped BLAST, BLASTP, BLASTN, or GCG. As used herein, the term “percent (%) amino acid sequence identity” with respect to aWSGR Docket No. 69143-712.601 sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the specific sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as EMBOSS MATCHER, EMBOSS WATER, EMBOSS STRETCHER, EMBOSS NEEDLE, EMBOSS LALIGN, BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignmait over the full length of the sequences being compared. In situations where ALIGN-2 is employed for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X / Y. whereXisthe number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in that program’ s alignment of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A. Unless specifically stated otherwise, all % amino acid sequence identity values used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program.

[0043] As used herein, the term “vector” is intended to refer to a nucleic acid molecule capable of transporting another nucleic acid to which it is attached.

[0044] As used herein, the term “host cell” refers to a cell into which an expression vector has beai introduced.

[0045] As used herein in the context of the structure of a polypeptide, “N-terminus” (or “amino terminus”) and “C-terminus” (or “carboxyl terminus”) generally refer to the extreme amino and carboxyl ends of the polypeptide, respectively.

[0046] As used herein, the terms “treat,” “treatment,” “treating,” or the like refer to administering a medicament or performing a procedure for the purpose of obtaining effects. These effects may be prophylactic in terms of completely or partially preventing a disease or a symptom thereof, and / or may be therapeutic in terms of achieving a partial or complete cure of a disease and / or a symptom of the disease. As used herein, “treating” can include treating a disease or disorder (e. g. , an inflammatory disease) in a mammal, particularly a human, and include: (a) preventing occurrence of the disease or symptoms of the disease in a subject who may be susceptible to the disease (e.g., including a disease that may be associated with or caused by the primary disease) but has not yet been diagnosed with the disease; (b) suppressing the disease, i. e. , stopping its progression; and (c) mitigating the disease, i.e., causing the disease to subside. Treatment may refer to an indicator of any success in the treatment or amelioration or prevention of cancer, including any objective or subjective parameters such as a reduction in symptoms; mitigation; elimination of disease symptoms or making the disease or disorder more tolerable to theWSGR Docket No. 69143-712.601 patient; slowing the rate of deterioration or decline; or making the final node of deterioration less debilitating The treatment or amelioration of symptoms is based on one or more objective or subjective parameters; including the results of a physician's examination. Accordingly, the term “treatment” includes administration of the antibody or composition or conjugate disclosed herein to prevent or delay, mitigate, or arrest or inhibit the progression of a symptom or condition associated with a disease (e. g. , an inflammatory disease). The term “therapeutic effecf ’ refers to the reduction, elimination, or prevention of a disease, disease symptoms, or disease side effects in a subject.

[0047] The term “therapeutically effective amount,” as used herein, generally means the amount of a polypeptide variant or a polypeptide composition that, when administered to a patient for treating a disease or other undesirable medical condition, is sufficient to have a beneficial effect with respect to that disease or condition. The therapeutically effective amount will vary depending on the polypeptide variant or the polypeptide composition, the disease or condition and its severity, and the age, weight, etc. of the patient to be treated. Determining the therapeutically effective amount of a given polypeptide variant or a given polypeptide composition is generally within the ordinary skill of the art and requires no more than routine experimentation.

[0048] As used herein, the terms “about” and “approximately” are used interchangeably. Any numerals used herein with or without about / approximately are meant to cover any normal fluctuations appreciated by one of ordinary skill in the relevant art. F or example, the term “about” may refer to a range of values ± 10%, ±5%, ±2%, or ±1% of a specified value. By way of an example, For example, the phrase “about 50%” may include from 45% to 55%, from 48% to 52%, or from 49% to 51%.

[0049] As used herein, “heteromultimer” or “heteromultimeric protein” is a molecule comprising at least a first polypeptide and a second polypeptide, wherein the second polypeptide differs in amino acid sequence from the first polypeptide by at least one amino acid residue. In some embodiments, the heteromultimer has binding specificity for at least two different ligands or binding sites. The heteromultimer can comprise a “heterodimef ’ formed by the first and second polypeptide or can form higher order tertiary structures where polypeptides in addition to the first and second polypeptide are present.

[0050] The above definitions supersede any conflicting definition in any reference that is incorporated by reference herein. The fact that certain terms are defined, however, should not be considered as indicative that any term that is undefined is indefinite. Rather, all terms used are believed to describe the disclosure in terms such that one of ordinary skill can appreciate the scope and practice the present application.Antibody

[0051] B cells play an important role in the pathogenesis of inflammatory diseases, immune diseases and autoimmune diseases, including rheumatoid arthritis (RA), by the presence of autoantibodies in most patients which precede symptomatic onset and are associated with a more severe disease course. Additionally, B cells and plasma cells are present in inflamed synovial membrane which can form lymphoid aggregates. CD20 is expressed on activated and memory B cells, the compartment responsible for certain autoimmune disease pathology. There is a need for additional therapeutic approaches targeting B cells are needed.WSGR Docket No. 69143-712.601

[0052] T cell engagers (TCEs) are a class of drugs that work by redirecting T cells to recognize and kill B cells expressing a target of interest, including CD20. Disclosed herein is an anti both' that binds to CD20 and CD3 bispecific. The antibody has low affinity for CD3 and high affinity for CD20 to enable efficient T cell mediated killing while minimizing risk of cytokine release syndrome (CRS) associated with TCEs with high CD3 affinity.

[0053] Disclosed herein, in one aspect, is antibody or antigen-binding fragment thereof that binds to CD20 and CD3. In some embodiments, the antibody or antigen-binding fragment thereof is multispecific. In some embodiments, the antibody or antigen-binding fragment thereof comprises a bispecific antibody. In some embodiments, the antibody or antigen-binding fragment thereof comprises a heteromultimeric bispecific antibody. In some embodiments, the antibody or antigen-binding fragment thereof comprises a fragmait crystallizable region (Fc) domain. In some embodiments, the antibody or antigen-binding fragment thereof comprises an imbalanced bispecific antibody. In some embodiments, the antibody or antigen-binding fragmait thereof comprises a fragment antigen-binding (Fab) region. In some embodiments, the antibody or antigenbinding fragment thereof comprises two Fab regions, a first Fab and a second Fab.

[0054] In some embodiments, the antibody or antigen-binding fragment thereof disclosed herein binds to a first target and a second target. In some embodiments, the first target comprises CD20. In some embodiment^ the second target comprises CD3. In some embodiments, the first target comprises CD20 and the second target comprises CD3. In some embodiments, the first target comprises CD20. In some embodiments, the second target comprises CD3. In some embodiments, the first target comprises CD20 and the second target comprises CD3.

[0055] In some embodiments, the antibody or antigen-binding fragment thereof simultaneously binds to two different types of antigens. In some embodiments, the antibody or antigen-binding fragment thereof simultaneously binds to CD20 and CD3. In some embodiments, the antibody or antigen-binding fragment thereof has two arms. In some embodiments, each of the two arms comprises a heavy chain variable region and a light chain variable region. In some embodiments, the heavy chain variable region and the light chain variable region of the same arm bind to two different antigens. In some embodiments, the antibody or antigen-binding fragmait thereof comprises an immunoglobulin G (IgG). In some embodiments, the antibody or anti gen -binding fragmait thereof targets CD20 on a B cell and CD3 on T cell. In some embodiments, the antibody or antigen-binding fragment thereof has low binding affinity to CD3.

[0056] Disclosed herein, in one aspect, is antibody or antigen -binding fragment thereof that binds to CD20 and CD3. In some embodiments, the antibody or antigen-binding fragment thereof comprises a first polypeptide comprising a first heavy chain variable region (VH1) comprising complementarity determining region (CDR1) 1, CDR2, and CDR3. In some embodiments, the VH1-CDR1 comprises the amino acid sequence of SEQ ID NO: 1. In some embodiments, the VH1-CDR2 comprises the amino acid sequence of SEQ ID NO: 2. In some embodiments, the VH1-CDR3 comprises the amino acid sequence of SEQ ID NO: 3.

[0057] In some embodiments, the antibody or antigen-binding fragment thereof comprises a second polypeptide comprising a second heavy chain variable region (VH2) comprising CDR1, CDR2, and CDR3. In some embodiments, the VH2-CDR1 comprises the amino acid sequence of SEQ IDNO: 4. In some embodiment^ the VH2-CDR2 comprises the amino acid sequence of SEQ ID NO: 5. In some embodiments, the VH2-CDR3WSGR Docket No. 69143-712.601 comprises the amino acid sequence of SEQ ID NO: 6. In some embodiments, the antibody or antigen-binding fragment thereof comprises a third polypeptide comprising a first light chain variable region (VL1) comprising CDR1, CDR2, and CDR3. In some embodiments, the VL1-CDR1 comprises the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VL1-CDR2 comprises the amino acid sequence of SEQ ID NO: 8. In some embodiments, the VL1-CDR3 comprises the amino acid sequence of SEQ ID NO: 9. In some embodiments, the antibody or antigen-binding fragment thereof comprises a fourth polypeptide comprising a second light chain variable region (VL2) comprising CDR1, CDR2, and CDR3. In some embodiments, the VL2-CDR1 comprises the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VL2-CDR2 comprises the amino acid sequence of SEQ ID NO: 8. In some embodiments, the VL2-CDR3 comprises the amino acid sequence of SEQ ID NO: 9.

[0058] In some embodiments, an isoelectric point is the pH at which a polypeptide has no net charge. In some embodiments, when the pH is higher than the isoelectric point, a polypeptide has a net negative charge. In some embodiments, when the pH is lower than the isoelectric point, a polypeptide has a net positive charge. In some embodiments, the VH1 comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 16 and an amino acid mutation with reference to SEQ ID NO: 16. In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO: 16 with an amino acid mutation with reference to SEQ ID NO: 16. In some embodiments, the VH1 comprises an amino acid mutation with reference to SEQ ID NO: 16 that changes an isoelectric point of SEQ ID NO: 16. In some embodiments, the amino acid mutation of VH1 comprises an amino acid substitution of threonine (T) with arginine (R). In some embodiments, the amino acid mutation of VH1 comprises an amino acid substitution of threonine (T) at amino acid residue 83 of SEQ ID NO: 16 according to the Kabat numbering scheme with arginine (R), or T83R mutation. In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO: 16 and an amino acid substitution of threonine (T) at amino acid residue 83 of SEQ ID NO: 16 according to the Kabat numbering scheme with arginine (R). In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO: 16 with the T83R mutation.

[0059] In some embodiments, the VH2 comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 17 and an amino acid mutation with reference to SEQ ID NO: 17. In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 and an amino acid mutation with reference to SEQ ID NO: 17. In some embodiments, the VH2 comprises an amino acid mutation that changes an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least two amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least three amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least four amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least five amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises five amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises an amino acid substitution of glutamine (Q) with glutamic acid, or glutamate (E). In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises anWSGR Docket No. 69143-712.601 amino acid substitution of glutamine (Q) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme with glutamate (E). In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least one amino acid substitution of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least two amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least three amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation ofVH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least four amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises five amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 with the Q to R mutations at each of amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17. In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 and an amino acid substitution of glutamine (Q) at each of amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17 according to the Kabat numbering scheme with glutamic acid (E).

[0060] In some embodiments, the antibody or antigen-binding fragment thereof further comprises a fragment crystaUizable (Fc) region. In some embodiments, the antibody or antigen-binding fragment thereof further comprises a fragment antigen-binding (Fab) region. In some embodiments, the antibody or antigen-binding fragment thereof further comprises two Fab regions. In some embodiments, the first polypeptide associates with the third polypeptide to form a first Fab region and the second polypeptide associates with the fourth polypeptide to form a second Fab region. In some embodiments, the first Fab region binds to CD20 and CD3. In some embodiments, the second Fab region binds to CD20 and CD3. In some embodiments, the first Fab region binds to CD20 and CD3 and the second Fab region binds to CD20 and CD3.

[0061] In some embodiments, the first polypeptide comprises a first heavy chain constant region 3 (CH3) comprising a first amino acid mutation with reference to a wildtype CH3 sequence. In some embodiments, the first amino acid mutation results in a protrusion in the first polypeptide that is positioned in a cavity in the second polypeptide. In some embodiments, the first amino acid mutation results in a cavity in the first polypeptide that is positioned in a protrusion in the second polypeptide. In some embodiments, the first amino acid mutation comprises a substitution of amino acid residue 354 according to EU numbering with a bulky hydrophobic amino acid. In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), phenylalanine (F), or tryptophan (W). In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354WSGR Docket No. 69143-712.601 according to EU numbering with tyrosine (Y), or S354Y mutation. In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with phenylalanine (F), or S354F mutation. In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tryptophan (W), or S354W mutation. In some embodiments, the first amino acid mutation further comprises a substitution of amino acid residue 366 according to EU numbering with a bulky hydrophobic amino acid. In some embodiments, the first amino acid mutation comprises the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y), or T366Y mutation. In some embodiments, the first heavy chain CH3 comprises a lysine (K) at amino acid residue 360 according to EU numbering. In some embodiments, the second polypeptide comprises a second heavy chain CH3 comprising a second amino acid mutation with reference to a wildtype CH3 sequence. In some embodiments, the second amino acid mutation results in a protrusion in the second polypeptide that is positioned in a cavity in the first polypeptide. In some embodiments, the second amino acid mutation results in a cavity in the second polypeptide that is positioned in a protrusion in the first polypeptide. In some embodiments, the second amino acid mutation comprises a substitution of amino acid residue 347 according to EU numbering with an amino acid of negative charge. In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E) or aspartic acid (D). In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E), or Q347E mutation. In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with aspartic acid (D), or Q347D mutation. In some embodiments, the second amino acid mutation further comprises a substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T), or Y407T mutation. In some embodiments, the VH1 of the first polypeptide or VH2 of the second polypeptide comprises at least one amino acid mutation that alters an isoelectric point of the antibody or antigen-binding fragment thereof. In some embodiments, (a) the first heavy chain CH3 comprises the first amino acid mutation and a lysine (K) at amino acid residue 360 according to EU numbering and the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), or S354Y mutation and the substitution of threonine (T) at amino acid residue 366 according toEUnumberingwithtyrosine(Y), orT366Y mutation and (b) the second heavy chain CH3 comprises the second amino acid mutation comprising the substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E), or Q347E mutation and the substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T), or Y407T mutation.

[0062] In some embodiments, the engineered ionic bond and hydrophobic interaction described herein may be combined with knob-into-hole (KIH) mutations to promote heterodimer formation. In some embodiments, a heteromultimeric proteins described herein comprises the first CH3 domain and the second CH3 domain each comprising a knob-into-hole (KIH) residue. In some embodiments, the knob-into-hole residues comprises T366Y and Y407T. In some embodiments, the first CH3 domain comprises T366Y and S354Y, and the second CH3WSGR Docket No. 69143-712.601 domain comprises Y407T and Q347E. In some embodiments, the first CH3 domain comprises Y407T and S354Y, and the second CH3 domain comprises T366Y and Q347E.

[0063] In some embodiments, the antibody disclosed herein comprises the first polypeptide and / or the second polypeptide each comprising a heavy chain constant domain 2 (CH2). In sonic embodiments, the heteromultimeric antibody comprises an IgG Fc region. In some embodiments, the IgG Fc region comprises an IgGl, IgG2, IgG3, or IgG4 Fc region. In some embodiments, the first polypeptide is an antibody heavy chain, and / or the second polypeptide is an antibody heavy chain. In some embodiments, the heteromultimeric antibody comprises one or more antibody light chains.

[0064] In some embodiments, the antibody disclosed herein comprises: (a) a first heavy chain comprising from the N-terminus to the C-terminus: a first heavy chain variable domain (VH1), a first heavy chain constant domain 1 (CHI), a first heavy chain constant domain 2 (CH2), and the first CH3 domain; (b) a first light chain comprising from the N-terminus to the C-terminus: a first light chain variable domain (VL1), and a first light chain constant domain (CL); (c) a second heavy chain comprising from the N-terminus to the C-terminus: a second heavy chain variable domain (VH2); a second CHI; a second CH2, and the second CH3 domain; and (d) a second light chain comprising from the N-terminus to the C-terminus: a second light chain variable domain (VL2), and a second CL; wherein VH1 and VL1 associate to form a first antigen binding site that specifically binds to a first target, and VH2 and VL2 associate to form a second antigen binding site that specifically binds to a second target. In some embodiments, VL1 and VL2 have the same amino acid sequence. In some embodiment^ VL1 and VL2 have different amino acid sequences. In some embodiments, the first target and the second target are the same epitopes. In some embodiments, the first target and the second target are different epitopes of the same antigen. In some embodiments, the first target and the second target are different antigens. In some embodiments, the first antigen binding site specifically binds CD20 and the second antigen binding site specifically binds CD3, or the first antigen binding site specifically hinds CD3 and the second antigen binding site specifically binds CD20.

[0065] In some embodiments, the VH1 comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 10, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VH1 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 10. In some embodiment^ the VH1 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with atWSGR Docket No. 69143-712.601 least 99% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10.

[0066] In some embodiments, the VH2 comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 11, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VH2 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 11. In some embodiment^ the VH2 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO:11. In some embodiments, the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises the amino acid sequence of SEQ ID NO: 11.

[0067] In some embodiments, the VL1 comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 12, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VL1 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 12. In some embodiment^ the VL1 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO:12. In some embodiments, the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises the amino acid sequence of SEQ ID NO: 12.

[0068] In some embodiments, the VL2 comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 12, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VL2 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 12. In some embodiment^ the VL2 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 12. In someWSGR Docket No. 69143-712.601 embodiments, the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino add sequence with at least 90% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 95% sequence identity to SEQ IDNO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 95% sequence identity to SEQ IDNO: 12; and the VL2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1WSGR Docket No. 69143-712.601 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino add sequence with at least 99% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10; the VH2 comprises the amino acid sequence of SEQ ID NO: 11 ; the VL1 comprises the amino acid sequence of SEQ ID NO: 12; or the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10; the VH2 comprises the amino acid sequence of SEQ ID NO: 11; the VL1 comprises the amino acid sequence of SEQ ID NO: 12; and the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the first polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 13, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the second polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 14, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the third polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 15, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the fourth polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 15, e.g. , about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence withat least 80% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an aminoWSGR Docket No. 69143-712.601 acid sequence with at least 85% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence withat least 90% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO: 13; the second polypeptide comprises the amino acid sequence of SEQ ID NO: 14; the third polypeptide comprises the amino acid sequence of SEQ ID NO: 15; or the fourth polypeptide comprises the amino acid sequence of SEQ ID NO: 15. In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO: 13; the second polypeptide comprises the aminoWSGR Docket No. 69143-712.601 acid sequence of SEQ ID NO: 14; the third polypeptide comprises the amino acid sequence of SEQ ID NO: 15; and the fourth polypeptide comprises the amino acid sequence of SEQ ID NO: 15.

[0069] In some embodiments, the antibody or antigen-binding fragment thereof disclosed herein can inhibit, reduce, eliminate, kill, or depleting B cells. In some embodiments, the antibody or antigen-binding fragment thereof disclosed herein can enhance T cell function, for example, by increasing effector T cell proliferation and / or increasing gamma interferon production by the effector T cell (e.g., as compared to proliferation and / or cytokine production prior to treatment with the antibodies or antigen binding fragments). In some embodiments, the antibody or antigen-binding fragment thereof disclosed herein can enhance CD4+ effector T cell function, for example, by increasing CD4+ effector T cell proliferation and / or increasing gamma interferon production by the CD4+ effector T cell (e.g., as compared to proliferation and / or cytokine production prior to treatment with the antibodies or antigen binding fragments).

[0070] Table 1 lists exemplary antibody amino acid sequences.Table 1. Exemplary Antibody Amino Acid SequencesWSGR Docket No. 69143-712.601Pharmaceutical Compositions

[0071] Disclosed herein, in one aspect, is a pharmaceutical composition comprising the antibody or antigen antibody or antigen-binding fragment thereof that binds to CD20 and CD3.

[0072] For administration to a subject, the antibody or antigen antibody or antigen- binding fragment thereof that binds to CD20 and CD3 as disclosed herein, may be provided in a pharmaceutical composition together with one or more pharmaceutically acceptable carriers or excipients. The term “pharmaceutically acceptable carrier” includes, but is not limited to, any carrier that does not interfere with the effectiveness of the biological activity of the ingredients and that is not toxic to the patient to whom it is administered. Examples of suitable pharmaceutical carriers are well known in the art and include phosphate buffered saline solutions, water, emulsions, such as oil / water emulsions, various types of wetting agents, sterile solutions etc. Such carriers can be formulated by conventional methods and can be administered to the subj ect at a suitable dose. Preferably, the compositions are sterile. These compositions may also contain adjuvants such as preservative, emulsifying agentsWSGR Docket No. 69143-712.601 and dispersing agents. Prevention of the action of microorganisms may be ensured by the inclusion of various antibacterial and antifungal agents.

[0073] The pharmaceutical composition may be in any suitable form, (depending upon the desired method of administration). It may be provided in unit dosage form, may be provided in a sealed container and may be provided as part of a kit. Such akit may include instructions for use. It may include a plurality of said unit dosage forms.

[0074] The pharmaceutical composition may be adapted for administration by any appropriate route, including aparenteral (e. g. , subcutaneous, intramuscular, infusion, oral, or intravenous) route. Such compositions may be prepared by any method known in the art of pharmacy, for example by mixing the active ingredient with the carrier(s) or excipient(s) under sterile conditions. In some embodiments, a pharmaceutical composition disclosed herein is administered intravenously to a subject in need thereof.

[0075] Disclosed herein, in one aspect, is a pharmaceutical composition comprising an antibody or antigenbinding fragment thereof that binds to CD20 and CD3. In some embodiments, the pharmaceutical composition further comprises a buffer in an amount of about 3 mg / ml to about 4 mg / ml, e.g., about 3mg / ml, 3. Img / ml, 3.2mg / ml, 3.3mg / ml, 3.4mg / ml, 3.5mg / ml, 3.6mg / ml, 3.7mg / ml, 3.8mg / ml, 3.9mg / ml, or about 4mg / ml, or any concentration therebetween. In some embodiments, the pharmaceutical composition further comprises a stabilizing agent in an amount of about 25 mg / ml to about 35 mg / ml, e.g., 25mg / ml,26mg / ml, 27mg / ml, 28mg / ml, 29mg / ml, 30mg / ml, 31mg / ml, 32mg / ml, 33mg / ml, 34mg / ml, or about 35mg / ml, or any concentration therebetween. In some embodiments, the pharmaceutical composition further comprises a surfactant in an amount of about 0.1 mg / ml to about 0.3 mg / ml, e.g., about 0. Img / ml, O. l lmg / ml, 0. 12mg / ml, 0. 13mg / ml, 0.14mg / ml, 0.15mg / ml, 0. 16mg / ml, 0. 17mg / ml, 0.18mg / ml, 0. 19mg / ml, 0.2mg / ml, 0.21mg / ml, 0.22mg / ml, 0.23mg / ml, 0.24mg / ml, 0.25mg / ml, 0.26mg / ml, 0.27mg / ml, 0.28mg / ml, 0.29mg / ml, or about 0.3mg / ml, or any concentration therebetween.

[0076] Disclosed herein, in one aspect, is a pharmaceutical composition comprising: an antibody or antigenbinding fragment thereof that binds to CD20 and CD3; a buffer in an amount of about 3 mg / ml to about 4 mg / ml; a stabilizing agent in an amount of about 25 mg / ml to about 35 mg / ml; and a surfactant in an amount of about 0.1 mg / ml to about 0.3 mg / ml, In some embodiments, the buffer comprises L-histidine or L-histidine monohydrochloride. In some embodiments, the buffer comprises L-histidine. In some embodiments, the buffer comprises L-histidine monohydrochloride. In some embodiments, the stabilizing agent comprises arginine hydrochloride or methionine. In some embodiments, the stabilizing agent comprises arginine hydrochloride. In some embodiments, the stabilizing agent comprises methionine. In some embodiments, the surfactant comprises a polysorbate. In some embodiments, the buffer comprises L-histidine or L-histidine monohydrochloride; the stabilizing agent comprises arginine hydrochloride or methionine; or the surfactant comprises a polysorbate. In some embodiments, the buffer comprises L-histidine and L-histidine monohydrochloride; the stabilizing agent comprises arginine hydrochloride or methionine; and the surfactant comprises a polysorbate. In some embodiments, the buffer comprises L-histidine or L-histidine monohydrochloride; the stabilizing agent comprises arginine hydrochloride and methionine; and the surfactant comprises a polysorbate. In some embodiments, theWSGR Docket No. 69143-712.601 buffer comprises L-histidine and L-histidine monohydrochloride; the stabilizing agent comprises arginine hydrochloride and methionine; and the surfactant comprises a polysorbate. In some embodiments, the polysorbate comprises polysorbate 20, polysorbate 40, polysorbate 60, or polysorbate 80. In some embodiments, the polysorbate comprises polysorbate 20 or polysorbate 80. In some embodiments, the polysorbate comprises polysorbate 20. In some embodiments, the polysorbate comprises polysorbate 40. In some embodiments, the polysorbate comprises polysorbate 60. In some embodiments, the polysorbate comprises polysorbate 80. In some embodiments, the pharmaceutical composition comprises the buffer in an amount of about 3.5 mg / ml to about 3.6 mg / ml, e.g., about 3.5mg / ml, 3.51mg / ml, 3.52mg / ml, 3.53mg / ml, 3.54mg / ml, 3.55mg / ml, 3.56mg / ml, 3.57mg / ml, 3.58mg / ml, 3.59mg / ml, or about 3.6mg / ml, or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises the stabilizing agent in an amount of about 31 mg / ml. In some embodiments, the pharmaceutical composition comprises the surfactant in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition comprises: the buffer in an amount of about 3.5 mg / ml to about 3.6 mg / ml; the stabilizing agent in an amount of about 31 mg / ml; and the surfactant in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition comprises L-histidine in an amount of about 1.9 mg / ml to about 1.95 mg / ml, e.g., 1.90 mg / ml, 1.91 mg / ml, 1.92 mg / ml, 1.93 mg / ml, 1.94 mg / ml, or about 1.95 mg / ml, or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises L-histidine in an amount of about 1.92 mg / ml. In some embodiments, the pharmaceutical composition comprises L-histidine monohydrochloride in an amount of about 1.6 mg / ml to about 1.65 mg / ml, e.g., about 1.6mg / ml, 1.61mg / ml, 1.62mg / ml, 1.63mg / ml, 1.64mg / ml, or about 1.65mg / ml, or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises L-histidine monohydrochloride in an amount of about 1.61mg / ml. In some embodiments, the pharmaceutical composition comprises methionine in an amount of about 1.5 mg / ml. In some embodiments, the pharmaceutical composition comprises arginine hydrochloride in an amount of about 29 mg / ml to about 30 mg / ml, e.g., about 29mg / ml, 29. Img / ml, 29.2mg / ml, 29.3mg / ml, 29.4mg / ml, 29.5mg / ml, 29.6mg / ml, 29.7mg / ml, 29.8mg / ml, 29.9mg / ml, or about 30mg / ml, or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises arginine hydrochloride in an amount of about 29.5mg / ml. In some embodiments, the pharmaceutical composition comprises polysorbate 20 in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition comprises: L-histidine in an amount of about 1.9 mg / ml to about 1.95 mg / ml; L-histidine monohydrochloride is in an amount of about 1.6 mg / ml to about 1.65 mg / ml; arginine hydrochloride in an amount of about 29 mg / ml to about 30 mg / ml; methionine in an amount of about 1.5 mg / ml; and polysorbate 20 in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition comprises: L-histidine in an amount of about 1.92 mg / ml; L-histidine monohydrochloride is in an amount of about 1.61 mg / ml; arginine hydrochloride in an amount of about 29.5mg / ml; methionine in an amount of about 1.5 mg / ml; and polysorbate 20 in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition further comprises about 20 mg / ml of the antibody or antigen-binding fragment thereof.

[0077] In some embodiments, the antibody or antigen-binding fragment thereof disclosed herein binds to a first target and a second target. In some embodiments, the first target comprises CD20. In some embodiment^WSGR Docket No. 69143-712.601 the second target comprises CD3. In some embodiments, the first target comprises CD20 and the second target comprises CD3. In some embodiments, the first target comprises CD20. In some embodiments, the second target comprises CD3. In some embodiments, the first target comprises CD20 and the second target comprises CD3.

[0078] In some embodiments, the antibody or antigen-binding fragment thereof simultaneously binds to two different types of antigens. In some embodiments, the antibody or antigen-binding fragment thereof simultaneously binds to CD20 and CD3. In some embodiments, the antibody or antigen-binding fragment thereof has two arms. In some embodiments, each of the two arms comprises a heavy chain variable region and a light chain variable region. In some embodiments, the heavy chain variable region and the light chain variable region of the same arm bind to two different antigens. In some embodiments, the antibody or antigen-binding fragment thereof comprises an immunoglobulin G (IgG). In some embodiments, the antibody or antigen -binding fragment thereof targets CD20 on a B cell and CD3 on T cell. In some embodiments, the antibody or antigen-binding fragment thereof has low binding affinity to CD3.

[0079] Disclosed herein, in one aspect, is antibody or antigen -binding fragment thereof that binds to CD20 and CD3. In some embodiments, the antibody or antigen-binding fragment thereof comprises a first polypeptide comprising a first heavy chain variable region (VH1) comprising complementarity determining region (CDR1) 1, CDR2, and CDR3. In some embodiments, the VH1-CDR1 comprises the amino acid sequence of SEQ ID NO: 1. In some embodiments, the VH1-CDR2 comprises the amino acid sequence of SEQ ID NO: 2. In some embodiments, the VH1-CDR3 comprises the amino acid sequence of SEQ ID NO: 3. In some embodiment^ the antibody or antigen-binding fragment thereof comprises a second polypeptide comprising a second heavy chain variable region (VH2) comprising CDR1, CDR2, and CDR3. In some embodiments, the VH2-CDR1 comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the VH2-CDR2 comprises the amino acid sequence of SEQ ID NO: 5. In some embodiments, the VH2-CDR3 comprises the amino acid sequence of SEQ ID NO: 6. In some embodiments, the antibody or antigen -binding fragment thereof comprises a third polypeptide comprising a first light chain variable region (VL1) comprising CDR1, CDR2, and CDR3. In some embodiment^ the VL1-CDR1 comprises the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VL1-CDR2 comprises the amino acid sequence of SEQIDNO: 8. In some embodiments, the VL1 -CDR3 comprises the amino acid sequence of SEQ ID NO: 9. In some embodiments, the antibody or antigen -binding fragment thereof comprises a fourth polypeptide comprising a second light chain variable region (VL2) comprising CDR1 , CDR2, and CDR3. In some embodiments, the VL2-CDR1 comprises the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VL2-CDR2 comprises the amino acid sequence of SEQ ID NO: 8. In some embodiments, the VL2-CDR3 comprises the amino acid sequence of SEQ ID NO: 9.

[0080] In some embodiments, an isoelectric point is the pH at which a polypeptide has no net charge. In some embodiments, when the pH is higher than the isoelectric point, a polypeptide has a net negative charge. In some embodiments, when the pH is lower than the isoelectric point, a polypeptide has a net positive charge. In some embodiments, the VH1 comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 16 and an amino acid mutation with reference to SEQ ID NO: 16. In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO: 16 with an amino acid mutation with reference to SEQ IDWSGR Docket No. 69143-712.601NO: 16. In some embodiments, the VH1 comprises an amino acid mutation with reference to SEQ ID NO: 16 that changes an isoelectric point of SEQ ID NO: 16. In some embodiments, the amino acid mutation of VH1 comprises an amino acid substitution of threonine (T) with arginine (R). In some embodiments, the amino acid mutation of VH1 comprises an amino acid substitution of threonine (T) at amino acid residue 83 of SEQ ID NO: 16 according to the Kabat numbering scheme with arginine (R), or T83R mutation. In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO: 16 and an amino acid substitution of threonine (T) at amino acid residue 83 of SEQ ID NO: 16 according to the Kabat numbering scheme with arginine (R). In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO: 16 with the T83R mutation.

[0081] In some embodiments, the VH2 comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 17 and an amino acid mutation with reference to SEQ ID NO: 17. In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 and an amino acid mutation with reference to SEQ ID NO: 17. In some embodiments, the VH2 comprises an amino acid mutation that changes an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least two amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least three amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least four amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least five amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises five amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises an amino acid substitution of glutamine (Q) with glutamic acid, or glutamic acid (E). In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises an amino acid substitution of glutamine (Q) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme with glutamic acid (E). In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least one amino acid substitution of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least two amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least three amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation ofVH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least four amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises five amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 with the Q to R mutations at eachWSGR Docket No. 69143-712.601 of amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17. In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 and an amino acid substitution of glutamine (Q) at each of amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17 according to the Kabat numbering scheme with glutamic acid (E).

[0082] In some embodiments, the antibody or antigen-binding fragment thereof further comprises a fragment crystaUizable (Fc) region. In some embodiments, the antibody or antigen-binding fragment thereof further comprises a fragment antigen-binding (Fab) region. In some embodiments, the antibody or antigen-binding fragment thereof further comprises two Fab regions. In some embodiments, the first polypeptide associates with the third polypeptide to form a first Fab region and the second polypeptide associates with the fourth polypeptide to form a second Fab region. In some embodiments, the first Fab region binds to CD20 and CD3. In some embodiments, the second Fab region binds to CD20 and CD3. In some embodiments, the first Fab region binds to CD20 and CD3 and the second Fab region binds to CD20 and CD3.

[0083] In some embodiments, the first polypeptide comprises a first heavy chain constant region 3 (CH3) comprising a first amino acid mutation with reference to a wildtype CH3 sequence. In some embodiments, the first amino acid mutation results in a protrusion in the first polypeptide that is positioned in a cavity in the second polypeptide. In some embodiments, the first amino acid mutation results in a cavity in the first polypeptide that is positioned in a protrusion in the second polypeptide. In some embodiments, the first amino acid mutation comprises a substitution of amino acid residue 354 according to EU numbering with a bulky hydrophobic amino acid. In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), phenylalanine (F), or tryptophan (W). In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), or S354Y mutation. In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with phenylalanine (F), or S354F mutation. In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tryptophan (W), or S354W mutation. In some embodiments, the first amino acid mutation further comprises a substitution of amino acid residue 366 according to EU numbering with a bulky hydrophobic amino acid. In some embodiments, the first amino acid mutation comprises the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y), or T366Y mutation. In some embodiments, the first heavy chain CH3 comprises a lysine (K) at amino acid residue 360 according to EU numbering. In some embodiments, the second polypeptide comprises a second heavy chain CH3 comprising a second amino acid mutation with reference to a wildtype 013 sequence. In some embodiments, the second amino acid mutation results in a protrusion in the second polypeptide that is positioned in a cavity in the first polypeptide. In some embodiments, the second amino acid mutation results in a cavity in the second polypeptide that is positioned in a protrusion in the first polypeptide. In some embodiments, the second amino acid mutation comprises a substitution of amino acid residue 347 according to EU numbering with an amino acid of negative charge. In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamicWSGR Docket No. 69143-712.601 acid (E) or aspartic acid (D). In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E), or Q347E mutation In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with aspartic acid (D), or Q347D mutation. In some embodiments, the second amino acid mutation further comprises a substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T), or Y407T mutation. In some embodiments, the VH1 of the first polypeptide or VH2 of the second polypeptide comprises at least one amino acid mutation that alters an isoelectric point of the antibody or antigen-binding fragment thereof. In some embodiments, (a) the first heavy chain CH3 comprises the first amino acid mutation and a lysine (K) at amino acid residue 360 according to EU numbering and the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), or S354Y mutation and the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y), or T366Y mutation and (b) the second heavy chain CH3 comprises the second amino acid mutation comprising the substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E), or Q347E mutation and the substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T), or Y407T mutation. In some embodiments, the engineered ionic bond and hydrophobic interaction described herein may be combined with knob-into-hole (KIH) mutations to promote heterodimer formation. In some embodiments, aheteromultimeric proteins described herein comprises the first CH3 domain and the second CH3 domain each comprising a knob-into-hole (KIH) residue. In some embodiments, the knob-into-hole residues comprises T366Y and Y407T. In some embodiments, the first CH3 domain comprises T366Y and S354Y, and the second CH3 domain comprises Y407T and Q347E. In some embodiments, the first CH3 domain comprises Y407T and S354Y, and the second CH3 domain comprises T366Y and Q347E.

[0084] In some embodiments, the antibody disclosed herein comprises the first polypeptide and / or the second polypeptide each comprising a heavy chain constant domain 2 (CH2). In sonic embodiments, the heteromultimeric antibody comprises an IgG Fc region. In some embodiments, the IgG Fc region comprises an IgGl, IgG2, IgG3, or IgG4 Fc region. In some embodiments, the first polypeptide is an antibody heavy chain, and / or the second polypeptide is an antibody heavy chain. In some embodiments, the heteromultimeric antibody comprises one or more antibody light chains. In some embodiments, the antibody disclosed herein comprises: (a) a first heavy chain comprising from the N-terminus to the C-terminus: a first heavy chain variable domain (VH1), a first heavy chain constant domain 1 (CHI), a first heavy chain constant domain 2 (CH2), and the first CH3 domain; (b) a first light chain comprising from the N-terminus to the C-terminus: a first light chain variable domain (VL1), and a first light chain constant domain (CL); (c) a second heavy chain comprising from the N- terminus to the C-terminus: a second heavy chain variable domain (VH2); a second CHI; a second CH2, and the second CH3 domain; and (d) a second light chain comprising from the N-terminus to the C-terminus: a second light chain variable domain (VL2), and a second CL; wherein VH1 and VL1 associate to form a first antigen binding site that specifically binds to a first target, and VH2 and VL2 associate to form a second antigen binding site that specifically binds to a second target. In some embodiments, VL1 and VL2 have the same amino acidWSGR Docket No. 69143-712.601 sequence. In some embodiments, VL1 and VL2 have different amino acid sequences. In some embodiments, the first target and the second target are the same epitopes. In some embodiments, the first target and the second target are different epitopes of the same antigen. In some embodiments, the first target and the second target are different antigens. In some embodiments, the first antigen binding site specifically binds CD20 and the second antigen binding site specifically binds CD3, or the first antigen binding site specifically hinds CD3 and the second antigen binding site specifically binds CD20.

[0085] In some embodiments, the VH1 comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 10, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VH1 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 10. In some embodiment^ the VH1 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO:10. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10. In some embodiments, the VH2 comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 11, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VH2 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO:11. In some embodiments, the VH2 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises the amino acid sequence of SEQ ID NO: 11. In some embodiments, the VL1 comprises an amino add sequence with about 70% to about 100% sequence identity to SEQ ID NO: 12, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VL1 comprises an amino acid sequence with at least 70% sequence identity to SEQ IDWSGR Docket No. 69143-712.601NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 75% sequence identity to SEQ IDNO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino add sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino add sequence with about 70% to about 100% sequence identity to SEQ ID NO: 12, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VL2 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 75% sequence identity to SEQ IDNO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino add sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino add sequence with at least 80% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 12; and the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1WSGR Docket No. 69143-712.601 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino add sequence with at least 90% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiment^ the VH1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10; the VH2 comprises the amino acid sequence of SEQ ID NO: 11; the VL1 comprises the amino acid sequence of SEQ ID NO: 12; or the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10; the VH2 comprises the amino acid sequence of SEQ ID NO: 11; the VL1 comprises the amino acid sequence of SEQ ID NO: 12; and the VL2 comprises the amino acid sequence of SEQ ID NO: 12.

[0086] In some embodiments, the first polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 13, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the second polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 14, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the third polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 15, e.g., about 70%, 71%, 72%, 73%, 74%,WSGR Docket No. 69143-712.60175%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the fourth polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQIDNO: 15, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween.

[0087] In some embodiments, the first polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQIDNO: 13; the second polypeptide comprises an amino acid sequence withat least 80% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 95% sequenceWSGR Docket No. 69143-712.601 identity to SEQIDNO: 13; the second polypeptide comprises an amino acid sequence withat least 95% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO: 13; the second polypeptide comprises the amino acid sequence of SEQ ID NO: 14; the third polypeptide comprises the amino acid sequence of SEQ ID NO: 15; or the fourth polypeptide comprises the amino acid sequence of SEQ ID NO: 15. In some embodiments, the first polypeptide comprises the amino acid sequence ofSEQID NO: 13; the second polypeptide comprises the amino acid sequence of SEQ ID NO: 14; the third polypeptide comprises the amino acid sequence of SEQ ID NO: 15; and the fourth polypeptide comprises the amino acid sequence of SEQ IDNO: 15.

[0088] In some embodiments, the pharmaceutical composition comprises a nucleic acid molecule encoding the antibody or antigen-binding fragment thereof In some embodiments, the pharmaceutical composition farther comprises a vector comprising the nucleic acid molecule. In some embodiments, the pharmaceutical composition further comprises a cell expressing the antibody or antigen -binding fragment thereof. In some embodiment^ the cell comprises the nucleic acid molecule encoding the antibody or antigen -binding fragment thereof. In some embodiments, the cell comprises the vector comprising the nucleic acid sequence. In some embodiments, the nucleic acid molecule comprises DNA or RNA. In some embodiments, the nucleic acid molecule comprises mRNA. In some embodiments, the pharmaceutical composition further comprises a lipid particle comprising the nucleic acid molecule. In some embodiments, the pharmaceutical composition further comprises a lipid nanoparticle comprising the nucleic acid molecule. In some embodiments, the pharmaceutical composition further comprises administering a lipid nanoparticle comprising mRNA encoding the antibody or antigen-binding fragment thereof.Methods of Treatment

[0089] Disclosed herein, in one aspect, is a method of treating an immune or inflammatory disease in a subject using an antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, antibody or antigen-binding fragment thereof binds to CD20 and CD3.WSGR Docket No. 69143-712.601

[0090] Disclosed herein, in one aspect, is a method of treating an immune or inflammatory disease, comprising administering to a subject in need thereof atherapeutically effective amount of an antibody or antigenbinding fragment thereof that binds to CD20 and CD3, thereby treating the immune or inflammatory disease.

[0091] Disclosed herein, in one aspect, is a method of eliminating, inhibiting, reducing, or depleting an immune cell in a subject using an antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, antibody or antigen-binding fragment thereof binds to CD20 and CD3.

[0092] Disclosed herein, in one aspect, is a method of eliminating, inhibiting, reducing, or depleting an immune cell in a subject, comprising administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof that binds to CD20 and CD3, thereby eliminating, inhibiting, reducing, or depleting the immune cell.

[0093] In some embodiments, the antibody or antigen-binding fragment thereof disclosed herein binds to a first target and a second target. In some embodiments, the first target comprises CD20. In some embodiment^ the second target comprises CD3. In some embodiments, the first target comprises CD20 and the second target comprises CD3. In some embodiments, the first target comprises CD20. In some embodiments, the second target comprises CD3. In some embodiments, the first target comprises CD20 and the second target comprises CD3.

[0094] In some embodiments, the antibody or antigen-binding fragment thereof simultaneously binds to two different types of antigens. In some embodiments, the antibody or antigen-binding fragment thereof simultaneously binds to CD20 and CD3. In some embodiments, the antibody or antigen-binding fragment thereof has two arms. In some embodiments, each of the two arms comprises a heavy chain variable region and a light chain variable region. In some embodiments, the heavy chain variable region and the light chain variable region of the same arm bind to two different antigens. In some embodiments, the antibody or antigen-binding fragment thereof comprises an immunoglobulin G (IgG). In some embodiments, the antibody or antigen -binding fragment thereof targets CD20 on a B cell and CD3 on T cell. In some embodiments, the antibody or antigen-binding fragment thereof has low binding affinity to CD3.

[0095] Disclosed herein, in one aspect, is antibody or antigen -binding fragment thereof that binds to CD20 and CD3. In some embodiments, the antibody or antigen-binding fragment thereof comprises a first polypeptide comprising a first heavy chain variable region (VH1) comprising complementarity determining region (CDR1) 1, CDR2, and CDR3. In some embodiments, the VH1-CDR1 comprises the amino acid sequence of SEQ ID NO: 1. In some embodiments, the VH1-CDR2 comprises the amino acid sequence of SEQ ID NO: 2. In some embodiments, the VH1-CDR3 comprises the amino acid sequence of SEQ ID NO: 3. In some embodiments, the antibody or antigen-binding fragment thereof comprises a second polypeptide comprising a second heavy chain variable region (VH2) comprising CDR1, CDR2, and CDR3. In some embodiments, the VH2-CDR1 comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the VH2-CDR2 comprises the amino acid sequence of SEQ ID NO: 5. In some embodiments, the VH2-CDR3 comprises the amino acid sequence of SEQ ID NO: 6. In some embodiments, the antibody or antigen -binding fragment thereof comprises a third polypeptide comprising a first light chain variable region (VL1) comprising CDR1, CDR2, and CDR3. In some embodiment^ the VL1-CDR1 comprises the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VL1-CDR2WSGR Docket No. 69143-712.601 comprises the amino acid sequence of SEQIDNO: 8. In some embodiments, the VL1 -CDR3 comprises the amino acid sequence of SEQ ID NO: 9. In some embodiments, the antibody or antigen -binding fragment thereof comprises a fourth polypeptide comprising a second light chain variable region (VL2) comprising CDR1, CDR2, and CDR3. In some embodiments, the VL2-CDR1 comprises the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VL2-CDR2 comprises the amino acid sequence of SEQ ID NO: 8. In some embodiments, the VL2-CDR3 comprises the amino acid sequence of SEQ ID NO: 9.

[0096] In some embodiments, an isoelectric point is the pH at which a polypeptide has no net charge. In some embodiments, when the pH is higher than the isoelectric point, a polypeptide has a net negative charge. In some embodiments, when the pH is lower than the isoelectric point, a polypeptide has a net positive charge. In some embodiments, the VH1 comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 16 and an amino acid mutation with reference to SEQ ID NO: 16. In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO: 16 with an amino acid mutation with reference to SEQ ID NO: 16. In some embodiments, the VH1 comprises an amino acid mutation with reference to SEQ ID NO: 16 that changes an isoelectric point of SEQ ID NO: 16. In some embodiments, the amino acid mutation of VH1 comprises an amino acid substitution of threonine (T) with arginine (R). In some embodiments, the amino acid mutation of VH1 comprises an amino acid substitution of threonine (T) at amino acid residue 83 of SEQ ID NO:16 according to the Kabat numbering scheme with arginine (R), or T83R mutation. In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO: 16 and an amino acid substitution of threonine (T) at amino acid residue 83 of SEQ ID NO: 16 according to the Kabat numbering scheme with arginine (R). In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO: 16 with the T83R mutation. In some embodiments, the VH2 comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:17 and an amino acid mutation with reference to SEQ ID NO: 17. In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 and an amino acid mutation with reference to SEQ ID NO: 17. In some embodiments, the VH2 comprises an amino acid mutation that changes an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least two amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least three amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least four amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least five amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises five amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises an amino acid substitution of glutamine (Q) with glutamic acid, or glutamic acid (E). In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises an amino acid substitution of glutamine (Q) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme with glutamic acid (E). In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least one amino acid substitution of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In someWSGR Docket No. 69143-712.601 embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least two amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least three amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least four amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises five amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 with the Q to R mutations at each of amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17. In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 and an amino acid substitution of glutamine (Q) at each of amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17 according to the Kabat numbering scheme with glutamic acid (E).

[0097] In some embodiments, the antibody or antigen-binding fragment thereof further comprises a fragment crystaUizable (Fc) region. In some embodiments, the antibody or antigen-binding fragment thereof further comprises a fragment antigen-binding (Fab) region. In some embodiments, the antibody or antigen-binding fragment thereof further comprises two Fab regions. In some embodiments, the first polypeptide associates with the third polypeptide to form a first Fab region and the second polypeptide associates with the fourth polypeptide to form a second Fab region. In some embodiments, the first Fab region binds to CD20 and CD3. In some embodiments, the second Fab region binds to CD20 and CD3. In some embodiments, the first Fab region binds to CD20 and CD3 and the second Fab region binds to CD20 and CD3.

[0098] In some embodiments, the first polypeptide comprises a first heavy chain constant region 3 (CH3) comprising a first amino acid mutation with reference to a wildtype CH3 sequence. In some embodiments, the first amino acid mutation results in a protrusion in the first polypeptide that is positioned in a cavity in the second polypeptide. In some embodiments, the first amino acid mutation results in a cavity in the first polypeptide that is positioned in a protrusion in the second polypeptide. In some embodiments, the first amino acid mutation comprises a substitution of amino acid residue 354 according to EU numbering with a bulky hydrophobic amino acid. In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), phenylalanine (F), or tryptophan (W). In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), or S354Y mutation. In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with phenylalanine (F), or S354F mutation. In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tryptophan (W), or S354W mutation. In some embodiments, the first amino acid mutation further comprises a substitution of amino acidWSGR Docket No. 69143-712.601 residue 366 according to EU numbering with a bulky hydrophobic amino acid. In some embodiments, the first amino acid mutation comprises the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y), or T366Y mutation. In some embodiments, the first heavy chain CH3 comprises a lysine (K) at amino acid residue 360 according to EU numbering. In some embodiments, the second polypeptide comprises a second heavy chain CH3 comprising a second amino acid mutation with reference to a wildtype CH3 sequence. In some embodiments, the second amino acid mutation results in a protrusion in the second polypeptide that is positioned in a cavity in the first polypeptide. In some embodiments, the second amino acid mutation results in a cavity in the second polypeptide that is positioned in a protrusion in the first polypeptide. In some embodiments, the second amino acid mutation comprises a substitution of amino acid residue 347 according to EU numbering with an amino acid of negative charge. In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E) or aspartic acid (D). In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E), or Q347E mutation In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with aspartic acid (D), or Q347D mutation. In some embodiments, the second amino acid mutation further comprises a substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T), or Y407T mutation. In some embodiments, the VH1 of the first polypeptide or VH2 of the second polypeptide comprises at least one amino acid mutation that alters an isoelectric point of the antibody or antigen-binding fragment thereof. In some embodiments, (a) the first heavy chain CH3 comprises the first amino acid mutation and a lysine (K) at amino acid residue 360 according to EU numbering and the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), or S354Y mutation and the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y), or T366Y mutation and (b) the second heavy chain CH3 comprises the second amino acid mutation comprising the substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E), or Q347E mutation and the substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T), or Y407T mutation.

[0099] In some embodiments, the engineered ionic bond and hydrophobic interaction described herein may be combined with knob-into-hole (KIH) mutations to promote heterodimer formation. In some embodiment^ a heteromultimeric proteins described herein comprises the first CH3 domain and the second CH3 domain each comprising a knob-into-hole (KIH) residue. In some embodiments, the knob-into-hole residues comprises T366Y and Y407T. In some embodiments, the first CH3 domain comprises T366Y and S354Y, and the second CH3 domain comprises Y407T and Q347E. In some embodiments, the first CH3 domain comprises Y407T and S354Y, and the second CH3 domain comprises T366Y and Q347E. In some embodiments, the antibody disclosed heron comprises the first polypeptide and / or the second polypeptide each comprising a heavy chain constant domain 2 (CH2). In sonic embodiments, the heteromultimeric antibody comprises an IgG Fc region. In some embodiment^ the IgGFc region comprises an IgGl, IgG2, IgG3, orIgG4 Fc region. In some embodiments, the first polypeptideWSGR Docket No. 69143-712.601 is an antibody heavy chain, and / or the second polypeptide is an antibody heavy chain. In some embodiments, the heteromultimeric antibody comprises one or more antibody light chains.

[0100] In some embodiments, the antibody disclosed herein comprises: (a) a first heavy chain comprising from the N-terminus to the C-terminus: a first heavy chain variable domain (VH1), a first heavy chain constant domain 1 (CHI), a first heavy chain constant domain 2 (CH2), and the first CH3 domain; (b) a first light chain comprising from the N-terminus to the C-terminus: a first light chain variable domain (VL1), and a first light chain constant domain (CL); (c) a second heavy chain comprising from the N-terminus to the C-terminus: a second heavy chain variable domain (VH2); a second CHI; a second CH2, and the second CH3 domain; and (d) a second light chain comprising from the N-terminus to the C-terminus: a second light chain variable domain (VL2), and a second CL; wherein VH1 and VL1 associate to form a first antigen binding site that specifically binds to a first target, and VH2 and VL2 associate to form a second antigen binding site that specifically binds to a second target. In some embodiments, VL1 and VL2 have the same amino acid sequence. In some embodiment^ VL1 and VL2 have different amino acid sequences. In some embodiments, the first target and the second target are the same epitopes. In some embodiments, the first target and the second target are different epitopes of the same antigen. In some embodiments, the first target and the second target are different antigens. In some embodiments, the first antigen binding site specifically binds CD20 and the second antigen binding site specifically binds CD3, or the first antigen binding site specifically hinds CD3 and the second antigen binding site specifically binds CD20.

[0101] In some embodiments, the VH1 comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 10, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VH1 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 10. In some embodiment^ the VH1 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10. In some embodiments, the VH2 comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 11, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VH2 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO:WSGR Docket No. 69143-712.60111. In some embodiments, the VH2 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises the amino acid sequence of SEQ ID NO: 11. In some embodiments, the VL1 comprises an amino add sequence with about 70% to about 100% sequence identity to SEQ ID NO: 12, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VL1 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 75% sequence identity to SEQ IDNO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino add sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino add sequence with about 70% to about 100% sequence identity to SEQ ID NO: 12, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VL2 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 75% sequence identity to SEQ IDNO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino add sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino add sequence with at least 80% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 80%WSGR Docket No. 69143-712.601 sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 12; and the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino add sequence with at least 90% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiment^ the VH1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10; the VH2 comprises the amino acid sequence of SEQ ID NO: 11; the VL1 comprises the amino acid sequence of SEQ ID NO: 12; or the VL2 comprises the amino acid sequence ofWSGR Docket No. 69143-712.601SEQ IDNO: 12. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10; the VH2 comprises the amino acid sequence of SEQ ID NO: 11; the VL1 comprises the amino acid sequence of SEQ ID NO: 12; and the VL2 comprises the amino acid sequence of SEQ ID NO: 12.

[0102] In some embodiments, the first polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 13, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the second polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 14, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the third polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 15, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the fourth polypeptide comprises an amino acid sequence with about 70% to about 100% sequaice identity to SEQ IDNO: 15, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15. In some embodiment^ the first polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence withat least 85% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 14; the thirdWSGR Docket No. 69143-712.601 polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence withat least 99% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO: 13; the second polypeptide comprises the amino acid sequence of SEQ ID NO: 14; the third polypeptide comprises the amino acid sequence of SEQ ID NO: 15; or the fourth polypeptide comprises the amino acid sequence of SEQ ID NO: 15. In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO: 13; the second polypeptide comprises the amino acid sequence of SEQ ID NO: 14; the third polypeptide comprises the amino acid sequence of SEQ ID NO: 15; and the fourth polypeptide comprises the amino acid sequence of SEQ ID NO: 15.

[0103] In some embodiments, the immune or inflammatory disease is mediated by a B cell, a plasmablast, or a plasma cell. In some embodiments, the immune or inflammatory disease is mediated by a B cell. In some embodiments, the immune or inflammatory disease is mediated by a plasmablast. In some embodiments, the immune or inflammatory disease is mediated by a plasma cell. In some embodiments, the immune or inflammatory disease is mediated by a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the immune or inflammatory disease is mediated by a mature B cell. In some embodiments, the immune or inflammatory disease is mediated by a memory B cell. In some embodiments, the immune orWSGR Docket No. 69143-712.601 inflammatory disease is mediated by an activated B cell. In some embodiments, the immune or inflammatory disease is mediated by an autoantibody. In some embodiments, the immune or inflammatory disease comprises an autoimmune disease.

[0104] In some embodiments, the immune or inflammatory disease comprises allergy, antibody-mediated rejection, alloantibodies, a disease related to or mediated by an alloantibody, amyloidosis, anti -glomerular basement membrane (GBM) (Goodpasture Syndrome), anti-N-methyl-D-aspartate receptor (NMD A) encephalitis (anti-NMDA-R Encephalitis), anti -neutrophil cytoplasmic autoantibody-associated vasculitis (ANCA vasculitis), antiphospholipid antibody syndrome, antisynthetase Syndrome, atopic dermatitis, autoimmune hepatitis, autoimmune necrotizing myopathy, Behcet’s disease, Bullous Pemphigoid, Celiac disease^ Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), connective tissue disease- associated interstitial lung disease (CTD-ILD), Crohn’s disease, dilated cardiomyopathy, Graves, Guillain Barre Syndrome^ Hidradenitis Suppurativa, idiopathic pulmonary fibrosis (IPF), IgA Nephropathy, Immunoglobulin G4-related disease (IgG4-RD), immune vasculitis (IgA), immune thrombocytopenia (ITP), interstitial lung disease (ILD), Long COVID, Lupus Nephritis, Membranous Nephropathy, microscopic polyangiitis, multiple sclerosis (MS) - primary progressive multiple sclerosis (MS-PPMS), multiple sclerosis (MS) -relapsing-remitting multiple sclerosis (MS-RRMS), myasthenia gravis (MG), myositis-dermatomyositis, myositis-inclusion body, myositispolymyositis, myositis- immune-mediated necrotizing myositis, neuromyelitis optica spectrum disorder (NMOSD), Pemphigus Vulgaris, polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome, Postural Orthostatic Tachycardia Syndrome (POTS), Polyarteritis Nodosa, Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis, Psoriasis, Psoriatic Arthritis, Raynaud’s Syndrome, Reactive Arthritis , rheumatoid arthritis, scleroderma or systemic sclerosis, Sjogren’s Syndrome, Stiff Person Syndrome, Systemic lupus, Systemic lupus erythematosus (SLE), lupus, Type 1 diabetes, Thyroid eye disease, tumor progression, or ulcerative colitis. In some embodiments, the immune or inflammatory disease comprises allergic rhinitis or hay fever, allergic rhinoconjunctivitis, allergic asthma, food allergy, drug allergy, insect sting allergy, urticaria, anaphylaxis, allergic bronchopulmonary aspergillosis (ABPA), allergic fungal sinusitis, atopic dermatitis or eczema, eosinophilic esophagitis, or eosinophilic gastroenteritis. In some embodiments, the immune or inflammatory disease comprises peanut allergy, shellfish allergy, milk allergy, egg allergy, IgE type drug allergy, bee sting allergy, wasp sting allergy, fire ant venom allergy, chronic spontaneous urticaria, or chronic inducible urticaria. In some embodiments, the immune or inflammatory disease comprises penicillin anaphylaxis.

[0105] In some embodiments, the immune or inflammatory disease is mediated by rheumatoid factor (RF) or anti-citrullinated protein antibodies (ACPA). In some embodiments, the immune or inflammatory disease is mediated by rheumatoid factor (RF). In some embodiments, the immune or inflammatory disease is mediated by anti-citrullinated protein antibodies (ACPA). In some embodiments, the immune or inflammatory disease comprises rheumatoid arthritis. In some embodiments, the immune or inflammatory disease comprises seropositive rheumatoid arthritis. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE). In some embodiments, the immune or inflammatory disease comprises seropositiveWSGR Docket No. 69143-712.601 systemic lupus erythematosus. In some embodiments, the immune or inflammatory disease comprises refractory seropositive systemic lupus erythematosus.

[0106] In some embodiments, the immune cell comprises a B cell, a plasmablast, or a plasma cell. In some embodiments, the immune cell comprises a B cell. In some embodiments, the immune cell comprises a plasmablast. In some embodiments, the immune cell comprises a plasma cell. In some embodiments, the immune cell comprises a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the immune cell comprises a mature B cell. In some embodiments, the immune cell comprises a memory B cell. In some embodiments, the immune cell comprises an activated B cell. In some embodiments, the administering results in a reduction, elimination, inhibition, or depletion of an immune cell or autoantibody. In some embodiments, the administering results in a reduction, elimination, inhibition, or depletion of an immune cell or autoantibody in serum. In some embodiments, the administering results in a rapid and persistent reduction, elimination, inhibition, or depletion of an immune cell or autoantibody in serum.

[0107] In some embodiments, the eliminating, inhibiting, reducing, or depleting the immune cell comprises resulting in a reduction of the immune cell by about 20% to about 100%, e.g. , about 20%, 21%, 22%, 23%, 24%,25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%,44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%,63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%,82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the immune cell comprises a B cell, a plasmablast, or a plasma cell. In some embodiments, the immune cell comprises a B cell. In some embodiments, the immune cell comprises a plasmablast. In some embodiments, the immune cell comprises a plasma cell. In some embodiments, the immune cell comprises a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the immune cell comprises a mature B cell. In some embodiments, the immune cell comprises a memory B cell. In some embodiments, the immune cell comprises an activated B cell. In some embodiment^ the eliminating, inhibiting, reducing, or depleting the immune cell comprises resulting in a reduction of an autoantibody by about 20% to about 100%, e.g., about 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%,49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%,68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%,87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the eliminating, inhibiting, reducing, or depleting the immune cell comprises resulting in a reduction of the immune cell by about 20% to about 100% in blood or bone marrow, eg, about 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%,38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%,57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%,76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%,95%, 96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the immuneWSGR Docket No. 69143-712.601 cell comprises a B cell, a plasmablast, or a plasma cell. In some embodiments, the immune cell comprises a B cell. In some embodiments, the immune cell comprises a plasmablast. In some embodiments, the immune cell comprises a plasma cell. In some embodiments, the immune cell comprises a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the immune cell comprises a mature B cell. In some embodiment^ the immune cell comprises a memory B cell. In some embodiments, the immune cell comprises an activated B cell. In some embodiments, the eliminating, inhibiting, reducing, or depleting the B cell comprises resulting in a reduction of the immune cell by about 20% to about 100% in blood or bone marrow, e. g. , about 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the eliminating, inhibiting, reducing, or depleting the immune cell comprises resulting in a reduction of the immune cell by about 20% to about 100%, e.g., about 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the immune cell comprises a B cell, a plasmablast, or a plasma cell. In some embodiments, the immune cell comprises a B cell. In some embodiments, the immune cell comprises a plasmablast. In some embodiments, the immune cell comprises a plasma cell. In some embodiments, the immune cell comprises a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the immune cell comprises a mature B cell. In some embodiments, the immune cell comprises a memory B cell. In some embodiments, the immune cell comprises an activated B cell. In some embodiments, the eliminating, inhibiting, reducing, or depleting the B cell comprises resulting in areduction of the immune cell by about 20% to about 100%, e.g., about20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the eliminating, inhibiting, reducing, or depleting the immune cell comprises resulting in a reduction of the immune cell by about 20% to about 100% in blood, e.g., about 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the immune cell comprises a B cell, a plasmablast, or a plasma cell. In some embodiments, theWSGR Docket No. 69143-712.601 immune cell comprises a B cell. In some embodiments, the immune cell comprises a plasmablast. In some embodiments, the immune cell comprises a plasma cell. In some embodiments, the immune cell comprises a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the immune cell comprises a mature B cell. In some embodiments, the immune cell comprises a memory B cell. In some embodiments, the immune cell comprises an activated B cell. In some embodiments, the eliminating, inhibiting, reducing, or depleting the B cell comprises resulting in a reduction of the immune cell by about 20% to about 100% in blood, e.g., about 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%,39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%,58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%,77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%,96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the eliminating, inhibiting, reducing, or depleting the immune cell comprises resulting in a reduction of the immune cell by about 20% to about 100% in bone marrow, e.g., about 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the immune cell comprises a B cell, a plasmablast, or a plasma cell. In some embodiments, the immune cell comprises a B cell. In some embodiments, the immune cell comprises a plasmablast. In some embodiments, the immune cell comprises a plasma cell. In some embodiments, the immune cell comprises a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the immune cell comprises a mature B cell. In some embodiments, the immune cell comprises a memory B cell. In some embodiments, the immune cell comprises an activated B cell. In some embodiments, the eliminating, inhibiting, reducing, or depleting the B cell comprises resulting in a reduction of the immune cell by about 20% to about 100% in bone marrow, e.g., about 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the administering results in an increase in the expression of an activation biomarker in T cells. In some embodiments, the activation biomarker comprises CD69. In some embodiments, the administering results in the increase in the expression of CD69 in CD4 T cells or CD8 T cells. In some embodiments, the administering results in the increase in the expression of CD69 in CD4 T cells. In some embodiments, the administering results in the increase in the expression of CD69 in CD8 T cells. In some embodiments, the administering results in an increase of a cytokine. In some embodiments, the cytokine comprises interferon gamma (IFN-y). In some embodiments, the administering results in the reduction, elimination, inhibition, or depletion of the immune cell or autoantibody, the increase in the expression of the activation biomarker in T cel I s.WSGR Docket No. 69143-712.601 or an increase of the cytokine. In some embodiments, the administering results in the reduction, elimination, inhibition, or depletion of the immune cell or autoantibody, the increase in the expression of the activation biomarker in T cells, and an increase of the cytokine. In some embodiments, the antibody or antigen-binding fragment thereof has an half-maximal effective concentration (ECso) for the reduction, elimination, inhibition, or depletion of the immune cell or autoantibody, the increase in the expression of the activation biomarker in T cel I s, or the increase of the cytokine, wherein the ECso value of the subject is the same as or similar to the ECso value of a healthy individual. In some embodiments, the antibody or antigen-binding fragment thereof has an half- maximal effective concentration (ECso) for the reduction, elimination, inhibition, or depletion of the immune cell or autoantibody, wherein the ECso value of the subject is the same as or similar to the ECso value of a healthy individual. In some embodiments, the antibody or antigen-binding fragment thereof has an half-maximal effective concentration (ECso) for the increase in the expression of the activation biomarker in T cells, wherein the ECso value of the subject is the same as or similar to the ECso value of a healthy individual. In some embodiment^ the antibody or antigen-binding fragment thereof has an half-maximal effective concentration (ECso) for the increase of the cytokine, wherein the ECso value of the subject is the same as or similar to the ECso value of a healthy individual. In some embodiments, the ECso value of the subject with rheumatoid arthritis or systemic lupus erythematosus (SLE) is the same as or similar to the ECso value of the healthy individual. In some embodiments, the ECso value of the subject with rheumatoid arthritis is the same as or similar to the ECso value of the healthy individual. In some embodiments, the ECso value of the subject with systemic lupus erythematosus (SLE) is the same as or similar to the ECso value of the healthy individual. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of: tissue B cells, autoantibodies, immunoglobulins, and / or tissue immune deposits. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of: tissue B cells, autoantibodies, immunoglobulins, or tissue immune deposits. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of: tissue B cells, autoantibodies, immunoglobulins, and tissue immune deposits. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of tissue B cells. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of: autoantibodies. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of: immunoglobulins. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of: tissue immune deposits. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of: (a) B cells in spleen; (b) doublestranded DNA (dsDNA) in serum; (c) total immunoglobulin G (IgG) in serum; and / or (d) IgG deposits in kidney.WSGR Docket No. 69143-712.601In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of: (a) B cells in spleen; (b) double-stranded DNA (dsDNA) in serum; (c) total immunoglobulin G (IgG) in serum; or (d) IgG deposits in kidney. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of: (a) B cells in spleen; (b) double-stranded DNA (dsDNA) in serum; (c) total immunoglobulin G (IgG) in serum; and (d) IgG deposits in kidney. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of B cells in spleen. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of double-stranded DNA (dsDNA) in serum. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of total immunoglobulin G (IgG) in serum. In some embodiments, the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in in the reduction, elimination, inhibition, or depletion of IgG deposits in kidney. In some embodiments, the administering results in about 20% to 100% reduction of dsDNA in serum, e.g., about 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%,47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%,66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%,85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the administering results in about 90% to 100% reduction of dsDNA in serum. In some embodiments, the administering results in a 90% reduction of dsDNA in serum. In some embodiments, the reduction, elimination, inhibition, or depletion starts within 7 days after the administering. In some embodiments, the reduction, elimination, inhibition, or depletion lasts for at least 14 days after the administering. In some embodiments, the immune cell comprises a B cell, a plasmablast, or a plasma cell. In some embodiments, the immune cell comprises a mature B cell, a memory B cell, or an activated B cell.

[0108] In some embodiments, the method further comprises administering to the subject a pharmaceutical composition comprising the antibody or antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition further comprises a buffer in an amount of about 3 mg / ml to about 4 mg / ml, e.g, about 3mg / ml, 3. Img / ml, 3.2mg / ml, 3.3mg / ml, 3.4mg / ml, 3.5mg / ml, 3.6mg / ml, 3.7mg / ml, 3.8mg / ml, 3.9mg / ml, or about 4mg / ml, or any concentration therebetween. In some embodiments, the pharmaceutical composition further comprises a stabilizing agent in an amount of about 25 mg / ml to about 35 mg / ml, e. g. , 25mg / ml, 26mg / ml, 27mg / ml, 28mg / ml, 29mg / ml, 30mg / ml, 31mg / ml, 32mg / ml, 33mg / ml, 34mg / ml, or about 35mg / ml, or any concentration therebetween. In some embodiments, the pharmaceutical composition further comprises a surfactant in an amount of about 0. 1 mg / ml to about 0.3 mg / ml, e.g., about 0. Img / ml, 0. 1 Img / ml, 0. 12mg / ml, 0.13mg / ml, 0. 14mg / ml, 0. 15mg / ml, 0.16mg / ml, 0. 17mg / ml, 0. 18mg / ml, 0.19mg / ml, 0.2mg / ml, 0.21mg / ml,WSGR Docket No. 69143-712.6010.22mg / ml, 0.23mg / ml, 0.24mg / ml, 0.25mg / ml, 0.26mg / ml, 0.27mg / ml, 0.28mg / ml, 0.29mg / ml, or about 0.3mg / ml, or any concentration therebetween.

[0109] Disclosed herein, in one aspect, is a pharmaceutical composition comprising: an antibody or antigenbinding fragment thereof that binds to CD20 and CD3; a buffer in an amount of about 3 mg / ml to about 4 mg / ml; a stabilizing agent in an amount of about 25 mg / ml to about 35 mg / ml; and a surfactant in an amount of about 0.1 mg / ml to about 0.3 mg / ml, In some embodiments, the buffer comprises L-histidine or L-histidine monohydrochloride. In some embodiments, the buffer comprises L-histidine. In some embodiments, the buffer comprises L-histidine monohydrochloride. In some embodiments, the stabilizing agent comprises arginine hydrochloride or methionine. In some embodiments, the stabilizing agent comprises arginine hydrochloride. In some embodiments, the stabilizing agent comprises methionine. In some embodiments, the surfactant comprises a polysorbate. In some embodiments, the buffer comprises L-histidine or L-histidine monohydrochloride; the stabilizing agent comprises arginine hydrochloride or methionine; or the surfactant comprises a polysorbate. In some embodiments, the buffer comprises L-histidine and L-histidine monohydrochloride; the stabilizing agent comprises arginine hydrochloride or methionine; and the surfactant comprises a polysorbate. In some embodiments, the buffer comprises L-histidine or L-histidine monohydrochloride; the stabilizing agent comprises arginine hydrochloride and methionine; and the surfactant comprises a polysorbate. In some embodiments, the buffer comprises L-histidine and L-histidine monohydrochloride; the stabilizing agent comprises arginine hydrochloride and methionine; and the surfactant comprises a polysorbate. In some embodiments, the polysorbate comprises polysorbate 20, polysorbate 40, polysorbate 60, or polysorbate 80. In some embodiments, the polysorbate comprises polysorbate 20 or polysorbate 80. In some embodiments, the polysorbate comprises polysorbate 20. In some embodiments, the polysorbate comprises polysorbate 40. In some embodiments, the polysorbate comprises polysorbate 60. In some embodiments, the polysorbate comprises polysorbate 80.

[0110] In some embodiments, the pharmaceutical composition comprises the buffer in an amount of about 3.5 mg / ml to about 3.6 mg / ml, e.g., about 3.5mg / ml, 3.51mg / ml, 3.52mg / ml, 3.53mg / ml, 3.54mg / ml, 3.55mg / ml, 3.56mg / ml, 3.57mg / ml, 3.58mg / ml, 3.59mg / ml, or about 3.6mg / ml, or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises the stabilizing agent in an amount of about 31 mg / ml. In some embodiments, the pharmaceutical composition comprises the surfactant in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition comprises: the buffer in an amount of about 3.5 mg / ml to about 3.6 mg / ml; the stabilizing agent in an amount of about 31 mg / ml; and the surfactant in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition comprises L-histidine in an amount of about 1.9 mg / ml to about 1.95 mg / ml, e.g., 1.90 mg / ml, 1.91 mg / ml, 1.92 mg / ml, 1.93 mg / ml, 1.94 mg / ml, or about 1.95 mg / ml, or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises L-histidine in an amount of about 1.92 mg / ml. In some embodiments, the pharmaceutical composition comprises L-histidine monohydrochloride in an amount of about 1.6 mg / ml to about 1.65 mg / ml, e.g., about 1.6mg / ml, 1.61mg / ml, 1.62mg / ml, 1.63mg / ml, 1.64mg / ml, or about 1.65mg / ml, or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises L-histidine monohydrochloride in an amount of about 1.61mg / ml. In some embodiments, the pharmaceutical composition comprises methionineWSGR Docket No. 69143-712.601 in an amount of about 1.5 mg / ml. In some embodiments, the pharmaceutical composition comprises arginine hydrochloride in an amount of about 29 mg / ml to about 30 mg / ml, e.g., about 29mg / ml, 29. Img / ml, 29.2mg / ml, 29.3mg / ml, 29.4mg / ml, 29.5mg / ml, 29.6mg / ml, 29.7mg / ml, 29.8mg / ml, 29.9mg / ml, or about 30mg / ml, or any concentration therebetween. In some embodiments, the pharmaceutical composition comprises arginine hydrochloride in an amount of about 29.5mg / ml. In some embodiments, the pharmaceutical composition comprises polysorbate 20 in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition comprises: L-histidine in an amount of about 1.9 mg / ml to about 1.95 mg / ml; L-histidine monohydrochloride is in an amount of about 1.6 mg / ml to about 1.65 mg / ml; arginine hydrochloride in an amount of about 29 mg / ml to about 30 mg / ml; methionine in an amount of about 1.5 mg / ml; and polysorbate 20 in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition comprises: L-histidine in an amount of about 1.92 mg / ml; L-histidine monohydrochloride is in an amount of about 1.61 mg / ml; arginine hydrochloride in an amount of about 29.5mg / ml; methionine in an amount of about 1.5 mg / ml; and polysorbate 20 in an amount of about 0.2 mg / ml. In some embodiments, the pharmaceutical composition further comprises about 20 mg / ml of the antibody or antigen-binding fragment thereof.

[0111] In some embodiments, the method further comprises administering a first dose of the antibody or antigen-binding fragment thereof. In some embodiments, the administering further comprises administering a first dose of the antibody or antigen-binding fragment thereof. In some embodiments, the method further comprises administering to the subj ect a target dose of the antibody or antigen-binding fragment thereof, wherein the target dose is administered after the first dose, wherein the target dose is the same as or higher than the first dose. In some embodiments, the method further comprises administering to the subject a second dose of the antibody or antigen-binding fragment thereof, wherein the second dose is administered between the first dose and the target dose, wherein the second dose is the same as or higher than the first dose and the target dose is the same as or higher than the second dose. In some embodiments, the method further comprises administering to the subject a third dose of the antibody or antigen-binding fragment thereof, wherein the third dose is administered between the second dose and the target dose, wherein the third dose is the same as or higher than the second dose and the target dose is the same as or higher than the third dose. In some embodiments, the method further comprises administering to the subj ect a fourth dose of the antibody or anti gen -binding fragment thereof, wherein the fourth dose is administered between the third dose and the target dose, wherein the fourth dose is the same as or higher than the third dose and the target dose is the same as or higher than the fourth dose. In some embodiments, wherein the first, second, third, fourth, or target dose comprises about 1 mg to about 100 mg of the antibody or antigen-binding fragment thereof, e.g., about Img, 2mg, 3mg, 4mg, 5mg, 6mg, 7mg, 8mg, 9mg, lOmg, l lmg, 12mg, 13mg, 14mg, 15mg, 16mg, 17mg, 18mg, 19mg, 20mg, 21mg, 22mg, 23mg, 24mg, 25mg,26mg, 27mg, 28mg, 29mg, 30mg, 3 Img, 32mg, 33mg, 34mg, 35mg, 36mg, 37mg, 38mg, 39mg, 40mg, 4 Img,42mg, 43mg, 44mg, 45mg, 46mg, 47mg, 48mg, 49mg, 50mg, 51mg, 52mg, 53mg, 54mg, 55mg, 56mg, 57mg,58mg, 59mg, 60mg, 61mg, 62mg, 63mg, 64mg, 65mg, 66mg, 67mg, 68mg, 69mg, 70mg, 71mg, 72mg, 73mg,74mg, 75mg, 76mg, 77mg, 78mg, 79mg, 80mg, 81mg, 82mg, 83mg, 84mg, 85mg, 86mg, 87mg, 88mg, 89mg,90mg, 91mg, 92mg, 93mg, 94mg, 95mg, 96mg, 97mg, 98mg, 99mg, or about lOOmg, or any dose therebetween.WSGR Docket No. 69143-712.601In some embodiments, wherein the first dose comprises about 1 mg to about 3 mg of the antibody or antigen - binding fragment thereof. In some embodiments, wherein the first dose comprises about 1 mg of the anti both' or antigen- binding fragment thereof. In some embodiments, wherein the first dose comprises about 1.5 mg of the antibody or antigen-binding fragment thereof. In some embodiments, wherein the first dose comprises about 2 mg of the antibody or antigen-binding fragment thereof. In some embodiments, wherein the first dose comprises about 2.5 mg of the antibody or antigen-binding fragment thereof. In some embodiments, wherein the first dose comprises about 3 mg of the antibody or antigen-binding fragment thereof. In some embodiments, the second dose comprises about 3 mg to about 10 mg of the antibody or antigen-binding fragment thereof, e.g., about 3mg, 4mg, 5mg, 6mg, 7mg, 8mg, 9mg, or about lOmg, or any dose therebetween. In some embodiments, the third, fourth, or target dose is about 3 mg to about 100 mg of the antibody or antigen-binding fragment thereof, e.g, about 3mg, 4mg, 5mg, 6mg, 7mg, 8mg, 9mg, lOmg, l lmg, 12mg, 13mg, 14mg, 15mg, 16mg, 17mg, 18mg, 19mg, 20mg, 21mg, 22mg, 23mg, 24mg, 25mg, 26mg, 27mg, 28mg, 29mg, 30mg, 31mg, 32mg, 33mg, 34mg,35mg, 36mg, 37mg, 38mg, 39mg, 40mg, 41mg, 42mg, 43mg, 44mg, 45mg, 46mg, 47mg, 48mg, 49mg, 50mg,51mg, 52mg, 53mg, 54mg, 55mg, 56mg, 57mg, 58mg, 59mg, 60mg, 61mg, 62mg, 63mg, 64mg, 65mg, 66mg,67mg, 68mg, 69mg, 70mg, 71mg, 72mg, 73mg, 74mg, 75mg, 76mg, 77mg, 78mg, 79mg, 80mg, 81mg, 82mg,83mg, 84mg, 85mg, 86mg, 87mg, 88mg, 89mg, 90mg, 91mg, 92mg, 93mg, 94mg, 95mg, 96mg, 97mg, 98mg,99mg, or about lOOmg, or any dose therebetween. In some embodiments, wherein the first dose is about 1 mg. In some embodiments, wherein the first dose is about 2 mg. In some embodiments, wherein the first dose is about 3 mg. In some embodiments, wherein the second dose is about 3 mg. In some embodiments, wherein the second dose is about 4 mg. In some embodiments, wherein the second dose is about 5 mg. In some embodiments, wherein the second dose is about 6 mg. In some embodiments, wherein the second dose is about 7 mg. In some embodiments, wherein the second dose is about 8 mg. In some embodiments, wherein the second dose is about 9 mg. In some embodiments, the second dose is about 10 mg. In some embodiments, the third, fourth, or target dose is about 3 mg. In some embodiments, the third, fourth, or target dose is about 4 mg. In some embodiments, the third, fourth, or target dose is about 5 mg. In some embodiments, the third, fourth, or target dose is about 6 mg. In some embodiments, the third, fourth, or target dose is about 7 mg. In some embodiments, the third, fourth, or target dose is about 8 mg. In some embodiments, the third, fourth, or target dose is about 9 mg. In some embodiments, the third, fourth, or target dose is about 10 mg. In some embodiments, the third, fourth, or target dose is about 20 mg. In some embodiments, thethird, fourth, or target dose is about30 mg. In some embodiment^ the third, fourth, or target dose is about 40 mg. In some embodiments, the third, fourth, or target dose is about 50 mg. In some embodiments, the third, fourth, or target dose is about 60 mg. In some embodiments, the third, fourth, or target dose is about 70 mg. In some embodiments, the third, fourth, or target dose is about 80 mg. In some embodiments, the third, fourth, or target dose is about 90 mg. In some embodiments, the third, fourth, or target dose is about 100 mg. In some embodiments, the first dose and the target dose are about 1 mg and about 3 mg, respectively. In some embodiments, the first dose and the target dose are about 3 mg and about 10 mg, respectively. In some embodiments, the first dose, the second dose, and the target dose are about 3 mg, about 10 mg, and about 10 mg, respectively. In some embodiments, the first dose, the second dose, and the target dose areWSGR Docket No. 69143-712.601 about 3 mg, about 10 mg, and about 30 mg, respectively. In some embodiments, the first dose, the second dose, and the target dose are about 3 mg, about 10 mg, and about 60 mg, respectively. In some embodiments, the first dose, the second dose, and the target dose are about 3 mg, about 10 mg, and about 100 mg, respectively. In some embodiments, two doses of the antibody or antigen-binding fragment thereof are administered at least 7 days apart. In some embodiments, the antibody or antigen-binding fragment thereof is administered on a weekly basis. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 8 days. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 9days. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 10 days. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 11 days. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 12 days. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 13 days. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 2 weeks. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 2.5 weeks. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 3 weeks. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 3.5 weeks. In some embodiments, the antibody or antigen-binding fragment thereof is administered once every 4 weeks. In some embodiments, the antibody or antigen-binding fragment thereof is administered at most 5 times in 29 days. In some embodiments, the first dose is about 1 mg and the target dose is about 3 mg, and the first dose and the target dose are administered on day 1 and day 8, respectively. In some embodiments, the first dose is about 3 mg and the target dose is about 10 mg, and the first dose and the target dose are administered on day 1 and day 8, respectively. In some embodiments, the first dose is about 3 mg, the second dose is about 10 mg and the target dose is about 10 mg, wherein the first dose, the second dose and the target dose are administered on day 1, day 8, and day 15, respectively. In some embodiments, the first dose is about 3 mg, the second dose is about 10 mg and the target dose is about 30 mg, and the first dose, the second dose and the target dose are administered on day 1, day 8, and day 15, respectively. In some embodiments, the first dose is about 3 mg, the second dose is about 10 mg and the target dose is about 60 mg, and the first dose, the second dose and the target dose are administered on day 1, day 8, and day 15, respectively. In some embodiments, the first dose is about 3 mg, the second dose is about 10 mg and the target dose is about 100 mg, and the first dose, the second dose and the target dose are administered on day 1, day 8, and day 15, respectively. In some embodiments, the target dose is administered at least twice, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, or at least 10 times. In some embodiment^ the target dose is administered once every week, once every 2 weeks, once every 3 weeks, once every 4 w eeks, or once in more than 4 weeks. In some embodiments, a dose of the antibody or antigen-binding fragment thereof is administered on day 22 or day 29. In some embodiments, a dose of the antibody or antigen-binding fragment thereof is administered on day 22. In some embodiments, a dose of the antibody or antigen-binding fragment thereof is administered on day 29. In some embodiments, a dose of the antibody or antigen-binding fragment thereof is administered on day 22 and day 29. In some embodiments, the target dose is administered on da' 22 or day 29. In some embodiments, the target dose is administered on day 22. In some embodiments, the target doseWSGR Docket No. 69143-712.601 is administered on day 29. In some embodiments, the target dose is administered on day 22 and day 29. In some embodiments, the method further comprises a treatment cycle comprising at least 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, or at least 6 weeks.

[0112] In some embodiments, the therapeutically effective amount of the antibody or antigen -binding fragment thereof is calculated based on a biomarker. In some embodiments, the biomarker comprises a B cell, a plasmablast, a plasma cell, rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), an autoantibody, or an immunoglobulin (Ig). In some embodiments, the biomarker comprises a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the biomarker comprises a free kappa light chain or a free lambda light chain. In some embodiments, the therapeutically effective amount is calculated based on an amount of the biomarker. In some embodiments, the biomarker comprises a B cell. In some embodiments, the biomarker comprises rheumatoid factor (RF). In some embodiments, the biomarker comprises anti-citrullinated protein antibody (ACPA). In some embodiments, the biomarker comprises an autoantibody. In some embodiments, the biomarker comprises an immunoglobulin (Ig). In some embodiments, the biomarker comprises a mature B cell. In some embodiments, the biomarker comprises amemory B cell. In some embodiments, the biomarker comprises an activated B cell. In some embodiments, the biomarker comprises a free kappa light chain. In some embodiments, the biomarker comprises a free lambda light chain. In some embodiments, the biomarker comprises an immunoglobulin (Ig). In some embodiments, the immunoglobulin comprises IgG, IgA, or IgM In some embodiments, the immunoglobulin comprises IgG. In some embodiments, the immunoglobulin comprises IgA. In some embodiments, the immunoglobulin comprises IgM. In some embodiments, the therapeutically effective amount is calculated based on an amount of the biomarker in blood or bone marrow. In some embodiments, the therapeutically effective amount is calculated based on a reduction in the amount of the biomarker in the blood or bone marrow after the administering. In some embodiments, the therapeutically effective amount is calculated based on a reduction in the amount of the biomarker in the blood after the administering. In some embodiments, the therapeutically effective amount is calculated based on a reduction in the amount of the biomarker in bone marrow after the administering. In some embodiments, the therapeutically effective amount results in a reduction of about 20% to about 100% of the biomarker after the administering, eg, about 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%,38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%,57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%,76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%,95%, 96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the antibody or antigen-binding fragment thereof is administered intramuscularly, intravenously, or subcutaneously. In some embodiments, the antibody or antigen-binding fragment thereof is administered intravenously or subcutaneously. In some embodiments, the antibody or antigen-binding fragment thereof is administered intravenously. In some embodiments, the antibody or antigen-binding fragment thereof is administered subcutaneously. In some embodiments, the antibody or antigen-binding fragment thereof is administered intramuscularly. In some embodiments, the subject is treated with a therapy for an adverse effect before, during, or after the administering.WSGR Docket No. 69143-712.601In some embodiments, the subj ect is treated with a therapy for an adverse effect before the administering. In some embodiments, the subject is treated with a therapy for an adverse effect during the administering. In some embodiments, the subject is treated with a therapy for an adverse effect after the administering. In some embodiments, the therapy comprises a corticosteroid, an antihistamine, or an antipyretic. In some embodiment^ the therapy comprises dexamethasone, methylprednisolone, diphenhydramine or an equivalent thereof, or acetaminophen or paracetamol or an equivalent thereof. In some embodiments, the therapy comprises about 20 mg of dexamethasone, about 80 mg of methylprednisolone, about 50 mg of diphenhydramine or an equivalent thereof, or about 650 mg to about 1 g of acetaminophen or paracetamol or an equivalent thereof. In some embodiments, the subject is treated with: the corticosteroid through intravenous administration at least 1 hour prior to the administering of the antibody or antigen-binding fragment thereof; the antihistamine through intravenous or intramuscular administration at least 30 min prior to the administering of the antibody or antigenbinding fragment thereof; the antihistamine through oral administration at least 1 h prior to the administering of the antibody or antigen-binding fragment thereof; or the antipyretic through oral administration at least 30 min prior to the administering of the antibody or antigen-binding fragment thereof. In some embodiments, the administering results in elimination or reduction of a B cell through antibody -dependent cellular cytotoxicity (ADCC). In some embodiments, the administering results in elimination of a B cell expressing CD20 through antibody-dependent cellular cytotoxicity (ADCC).

[0113] In some embodiments, the administering results in a reduction of about 20% to about 100% of a B cell, e.g., about 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%,56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%,75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,94%, 95%, 96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the administering results in a reduction of about 20% to about 100% of an autoantibody, e.g., about 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%,42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%,61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%,80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,99%, or about 100%, or any percentage therebetween. In some embodiments, the administering results in a reduction of about 20% to about 100% of a B cell in blood or bone marrow, e.g., about 20%, 21%, 22%, 23%,24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%,43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%,62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%,81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the administering results in a reduction of at least 20% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of at least 30% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of at leastWSGR Docket No. 69143-712.60140% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of at least 50% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of at least 60% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of at least 70% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of at least 80% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of at least 90% of a B cell or an autoantibody. In some embodiments, the administering results in a reduction of about 100% of a B cell or an autoantibody. In some embodiments, the method further comprises revaccinating the subject. In some embodiments, the administering does not result in a significant effect on a T cell. In some embodiments, the subject is treated with a therapy for neutropenia, anemia, leukopenia, COVID- 19infection, hypokalemia, cytokine release syndrome, infection, thrombocytopenia, or an infusion-related reaction, before, during, or after the administering. In some embodiments, the subject is diagnosed with adult-onset rheumatoid arthritis based on the 2010 American College of Rheumatology (ACR) or European League Against Rheumatism (EULAR) classification criteria at least 3 months prior to the administering. In some embodiments, the subject is refractory to a prior treatment before the administering, wherein the prior treatment comprises a biologic disease-modifying antirheumatic drug (bDMARD) or a targeted synthetic disease-modifying antirheumatic drug (tsDMARD), wherein the subject exhibits inadequate treatment response, lack of clinical benefit, or poor tolerability after at least 12 weeks of the prior treatment. In some embodiments, the prior treatment comprises 2 bDMARDs in different mechanism classes, or 1 bDMARD and 1 tsDMARD. In some embodiments, the prior treatment comprises a tumor necrosis factor (INF) inhibitor. In some embodiments, the subject exhibits no intolerance to a prior B cell depletion therapy. In some embodiments, the subject exhibits moderate to severe active rheumatoid arthritis. In some embodiments, the subject has at least 6 / 68 tender joints and at least 6 / 66 swollen joints. In some embodiments, the subject tests positive for rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA). In some embodiments, the subject, prior to or during the administering, is treated with methotrexate (MTX), hydroxychloroquine, leflunomide, oral sulfasalazine, azathioprine, my cophenol ate, oral prednisone, a nonsteroidal anti-inflammatory drug, folic acid, or folinic acid. In some embodiments, the subject is not treated with a parenteral corticosteroid prior to the administering. In some embodiments, the subj ect has: detectable peripheral B cells in an amount of at least 25 cells / ml; absolute neutrophil count of at least 2.0 x 109 / L; platelet count of at least 100 x 109 / L; hemoglobin level of at least 10.0 g / dL; a lymphocyte count of more than 500 cells / pL; a total leukocyte count of at least 3.0 x 109 / L; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of at least 2 times of the upper limit of normal (ULN); and total bilirubin and alkaline phosphatase levels less than 1.5 time of the ULN, wherein the subj ect has serum direct bilirubin less than 1.5 mg / dL when the subj ect has Gilbert’s syndrome. In some embodiments, the subj ect does not have a class IV rheumatoid arthritis according to American College of Rheumatology (ACR) revised response criteria. In some embodiments, the subject does not have a history of a rheumatologic autoimmune disease other than rheumatoid arthritis . In some embodiment^ the subject does not have secondary Sjogren’s syndrome. In some embodiments, the subject does not have a significant systemic involvement secondary to rheumatoid arthritis. In some embodiments, the subject does not have Felty’s syndrome. In some embodiments, the subject does not have juvenile idiopathic arthritis or idiopathicWSGR Docket No. 69143-712.601 arthritis diagnosed before the age of 16 years. In some embodiments, the subject does not have psoriatic arthritis. In some embodiments, the subject does not have axial spondylarthritis or any other disease associated with inflammatory arthritis. In some embodiments, the subject does not have a prior rheumatoid arthritis treatment comprising: an anti-CD 19 therapy or an anti-CD20 therapy, optionally comprising blinatumomab, obinutuzumab, rituximab, ocrelizumab, or ofatumumab, less than 6 months prior to the administering. In some embodiments, the subject does not have a cell depleting therapy, optionally comprising an anti-CD4 therapy, anti-CD5 therapy, or an anti-CD3 therapy, less than 6 months prior to the administering. In some embodiments, the subject does not have a J AK inhibitor, a Bruton tyrosine kinase (BTK) inhibitor, oratyrosinekinase2 (TYK2) inhibitor, optionally comprising baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, fenebrutinib, deucravacitinib, brepocitinib, ropsacitinib, within 4 weeks prior to the administering. In some embodiments, the subject does not have an immunomodulatory bDMARD, optionally comprising adalimumab, golimumab, ustekinumab, secukinumab, tocilizumab, abatacept, etanercept, anakinra, infliximab, certolizumab pegol, IL-6, IL-23, or IL- 17, less than 12 weeks or 5 half-lives, prior to the administering. In some embodiments, the subj ect does not have an experimental CAR-T or TCE therapy less than 12 months prior to the administering. In some embodiments, the subject does not have a calcineurin inhibitor less than 8 weeks prior to the administering. In some embodiments, the subject does not have a cyclophosphamide less than 24 weeks prior to the administering. In some embodiments, the subject is not intolerant to a B cell depl eting therapy. In some embodiments, the subject does not have progressive multifocal leukoencephalopathy. In some embodiments, the subject does not have stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.

[0114] In another aspect, disclosed herein, is a method of treating an immune or inflammatory disease^ comprising: administering to a subject in need thereof a first dose of an antibody or antigen-binding fragment thereof that binds to CD20 and CD3; and measuring a biomarker in the subject. In some embodiments, the immune or inflammatory disease comprises allergy, antibody-mediated rejection, alloantibodies, a disease related to or mediated by an alloantibody, amyloidosis, anti -glomerular basement membrane (GBM) (Goodpasture Syndrome), anti-N-methyl-D-aspartate receptor (NMDA) encephalitis (anti-NMDA-R Encephalitis), antineutrophil cytoplasmic autoantibody-associated vasculitis (ANCA vasculitis), antiphospholipid antibody syndrome, antisynthetase Syndrome, atopic dermatitis, autoimmune hepatitis, autoimmune necrotizing myopathy, Behcet’s disease, Bullous Pemphigoid, Celiac disease, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), connective tissue disease- associated interstitial lung disease (CTD-ILD), Crohn’s disease, dilated cardiomyopathy, Graves, Guillain Barre Syndrome, Hidradenitis Suppurativa, idiopathic pulmonary fibrosis (IPF), IgA Nephropathy, Immunoglobulin G4-related disease (IgG4-RD), immune vasculitis (IgA), immune thrombocytopenia (ITP), interstitial lung disease (ILD), Long COVID, Lupus Nephritis^ Membranous Nephropathy, microscopic polyangiitis, multiple sclerosis (MS) - primary progressive multiple sclerosis (MS-PPMS), multiple sclerosis (MS) -relapsing-remitting multiple sclerosis (MS-RRMS), myasthenia gravis (MG), myositis-dermatomyositis, myositis-inclusion body, myositis-polymyositis, myositis- immune- mediated necrotizing myositis, neuromyelitis optica spectrum disorder (NMOSD), Pemphigus Vulgaris, polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome, PosturalWSGR Docket No. 69143-712.601Orthostatic Tachycardia Syndrome (POTS), Polyarteritis Nodosa, Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis, Psoriasis, Psoriatic Arthritis, Raynaud’s Syndrome, Reactive Arthritis, rheumatoid arthritis, scleroderma or systemic sclerosis, Sjogren’s Syndrome, Stiff Person Syndrome, Systemic lupus, Systemic lupus erythematosus (SLE), lupus, Type 1 diabetes, Thyroid eye disease, tumor progression, or ulcerative colitis. In some embodiments, the immune or inflammatory disease comprises allergic rhinitis or hay fever, allergic rhinoconjunctivitis, allergic asthma, food allergy, drug allergy, insect sting allergy, urticaria, anaphylaxis, allergic bronchopulmonary aspergillosis (ABPA), allergic fungal sinusitis, atopic dermatitis or eczema, eosinophilic esophagitis, or eosinophilic gastroenteritis. In some embodiments, the immune or inflammatory disease comprises peanut allergy, shellfish allergy, milk allergy, egg allergy, IgE type drug allergy, bee sting allergy, wasp sting allergy, fire ant venom allergy, chronic spontaneous urticaria, or chronic inducible urticaria. In some embodiments, the immune or inflammatory disease comprises penicillin anaphylaxis.

[0115] In some embodiments, the biomarker comprises a B cell, a plasmablast, a plasma cell, rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), an autoantibody, or an immunoglobulin (Ig). In some embodiments, the biomarker comprises a B cell. In some embodiments, the biomarker comprises a plasmablast. In some embodiments, the biomarker comprises a plasma cell. In some embodiments, the biomarker comprises rheumatoid factor (RF). In some embodiments, the biomarker comprises anti-citrullinated protein antibody (ACPA). In some embodiments, the biomarker comprises an autoantibody. In some embodiments, the biomarker comprises an immunoglobulin (Ig). In some embodiments, the biomarker comprises a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the biomarker comprises a mature B cell. In some embodiments, the biomarker comprises a memory B cell. In some embodiments, the biomarker comprises an activated B cell. In some embodiments, the biomarker comprises a free kappa light chain or a free lambda light chain. In some embodiments, the biomarker comprises a free kappa light chain. In some embodiments, the biomarker comprises a free lambda light chain. In some embodiments, the biomarker comprises a B cell, rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), or an immunoglobulin (Ig). In some embodiments, the immunoglobulin comprises IgG, IgA, or IgM. In some embodiments, the immune or inflammatory disease is mediated by a B cell, aplasmablast, a plasma cell, an autoantibody, or an immunoglobulin (Ig). In some embodiments, the immune or inflammatory disease is mediated by B-cell activating factor (BAFF). In some embodiments, the immune or inflammatory disease is mediated by a free kappa light chain or a free lambda light chain. In some embodiments, the Ig comprises IgG, IgA, or IgM. In some embodiments, the measuring comprises measuring an amount of the biomarker in blood or bone marrow after the administering the first dose. In some embodiments, the method further comprises, after the measuring, comparing the amount of the biomarker to a base level. In some embodiments, the method further comprises, after the comparing, calculating a reduction in an amount of the biomarker. In some embodiments, the reduction in the amount of the biomarker that is equal to or higher than a reference level indicates that the first dose is a therapeutically effective for treating the immune or inflammatory disease. In some embodiments, the reduction in the amount of the biomarker that is lower than the reference level indicates that the first dose is not therapeutically effective for treating the immune or inflammatory disease. In some embodiments, the reference level is about 20% to aboutWSGR Docket No. 69143-712.601100%, e.g., about 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100%, or any percentage therebetween. In some embodiments, the reference level is at least about 20%. In some embodiments, the reference level is at least about 30%. In some embodiments, the reference level is at least about 40%. In some embodiments, the reference level is at least about 50%. In some embodiments, the reference level is at least about 60%. In some embodiments, the reference level is at least about 70%. In some embodiments, the reference level is at least about 80%. In some embodiment^ the reference level is at least about 90%. In some embodiments, the reference level is at least about 95%. In some embodiments, the reference level is at least about 99%. In some embodiments, the reference level is about 100%.

[0116] In some embodiments, the method further comprises administering to the subject a second dose of the antibody or antigen-binding fragment thereof when the first dose is not therapeutically effective for treating the immune or inflammatory disease, wherein the second dose is higher than the first dose. In some embodiment^ the second dose is calculated based on an amount of the biomarker. In some embodiments, the second dose is calculated based on an amount of the biomarker in serum. In some embodiments, the second dose is calculated based on a reduction or an increase in the amount of the biomarker in the serum after the administering. In some embodiments, the measuring comprises measuring an amount of the biomarker in serum after the administering the first dose. In some embodiments, The method further comprises, after the measuring, comparing the amount of the biomarker to a base level. In some embodiments, the method further comprises, after the comparing, calculating a reduction or an increase in an amount of the biomarker. In some embodiments, the reduction or increase in the amount of the biomarker that is equal to or higher than a reference level indicates that the first dose is a therapeutically effective for treating the disease. In some embodiments, the immune or inflammatory disease is mediated by a B cell, a plasmablast, or a plasma cell. In some embodiments, the immune or inflammatory disease is mediated by a mature B cell, a memory B cell, or an activated B cell. In some embodiments, the immune or inflammatory disease is mediated by an autoantibody. In some embodiments, the immune or inflammatory disease comprises an autoimmune disease. In some embodiments, the immune or inflammatory disease is mediated by rheumatoid factor (RF) or anti-citrullinated protein antibodies (ACPA). In some embodiments, the immune or inflammatory disease comprises rheumatoid arthritis. In some embodiments, the immune or inflammatory disease comprises seropositive rheumatoid arthritis.

[0117] In some embodiments, the antibody or antigen-binding fragment thereof disclosed herein binds to a first target and a second target. In some embodiments, the first target comprises CD20. In some embodiment^ the second target comprises CD3. In some embodiments, the first target comprises CD20 and the second target comprises CD3. In some embodiments, the first target comprises CD20. In some embodiments, the second target comprises CD3. In some embodiments, the first target comprises CD20 and the second target comprises CD3. In some embodiments, the antibody or antigen-binding fragment thereof simultaneously binds to two different types of antigens. In some embodiments, the antibody or antigen-binding fragment thereof simultaneously binds toWSGR Docket No. 69143-712.601CD20 and CD3. In some embodiments, the antibody or antigen -binding fragment thereof has two arms. In some embodiments, each of the two arms comprises a heavy chain variable region and a light chain variable region In some embodiments, the heavy chain variable region and the light chain variable region of the same arm bind to two different antigens. In some embodiments, the antibody or antigen-binding fragment thereof comprises an immunoglobulin G (IgG). In some embodiments, the antibody or antigen-binding fragment thereof targets CD20 on a B cell and CD3 on T cell. In some embodiments, the antibody or antigen-binding fragment thereof has low binding affinity to CD3.

[0118] Disclosed herein, in one aspect, is antibody or antigen -binding fragment thereof that binds to CD20 and CD3. In some embodiments, the antibody or antigen-binding fragment thereof comprises a first polypeptide comprising a first heavy chain variable region (VH1) comprising complementarity determining region (CDR1) 1, CDR2, and CDR3. In some embodiments, the VH1-CDR1 comprises the amino acid sequence of SEQ ID NO: 1. In some embodiments, the VH1-CDR2 comprises the amino acid sequence of SEQ ID NO: 2. In some embodiments, the VH1-CDR3 comprises the amino acid sequence of SEQ ID NO: 3. In some embodiments, the antibody or antigen-binding fragment thereof comprises a second polypeptide comprising a second heavy chain variable region (VH2) comprising CDR1, CDR2, and CDR3. In some embodiments, the VH2-CDR1 comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the VH2-CDR2 comprises the amino acid sequence of SEQ ID NO: 5. In some embodiments, the VH2-CDR3 comprises the amino acid sequence of SEQ ID NO: 6. In some embodiments, the antibody or antigen -binding fragment thereof comprises a third polypeptide comprising a first light chain variable region (VL1) comprising CDR1, CDR2, and CDR3. In some embodiment^ the VL1-CDR1 comprises the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VL1-CDR2 comprises the amino acid sequence of SEQIDNO: 8. In some embodiments, the VL1 -CDR3 comprises the amino acid sequence of SEQ ID NO: 9. In some embodiments, the antibody or antigen -binding fragment thereof comprises a fourth polypeptide comprising a second light chain variable region (VL2) comprising CDR1 , CDR2, and CDR3. In some embodiments, the VL2-CDR1 comprises the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VL2-CDR2 comprises the amino acid sequence of SEQ ID NO: 8. In some embodiments, the VL2-CDR3 comprises the amino acid sequence of SEQ ID NO: 9.

[0119] In some embodiments, an isoelectric point is the pH at which a polypeptide has no net charge. In some embodiments, when the pH is higher than the isoelectric point, a polypeptide has a net negative charge. In some embodiments, when the pH is lower than the isoelectric point, a polypeptide has a net positive charge. In some embodiments, the VH1 comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 16 and an amino acid mutation with reference to SEQ ID NO: 16. In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO: 16 with an amino acid mutation with reference to SEQ ID NO: 16. In some embodiments, the VH1 comprises an amino acid mutation with reference to SEQ ID NO: 16 that changes an isoelectric point of SEQ ID NO: 16. In some embodiments, the amino acid mutation of VH1 comprises an amino acid substitution of threonine (T) with arginine (R). In some embodiments, the amino acid mutation of VH1 comprises an amino acid substitution of threonine (T) at amino acid residue 83 of SEQ ID NO: 16 according to the Kabat numbering scheme with arginine (R), or T83R mutation. In some embodiments, theWSGR Docket No. 69143-712.601VH1 comprises an amino acid sequence of SEQ ID NO: 16 and an amino acid substitution of threonine (T) at amino acid residue 83 of SEQ ID NO: 16 according to the Kabat numbering scheme with arginine (R). In some embodiments, the VH1 comprises an amino acid sequence of SEQ ID NO: 16 with the T83R mutation. In some embodiments, the VH2 comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 17 and an amino acid mutation with reference to SEQ ID NO: 17. In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 and an amino acid mutation with reference to SEQ ID NO: 17. In some embodiments, the VH2 comprises an amino acid mutation that changes an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least two amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least three amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least four amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises at least five amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the VH2 comprises five amino acid mutations that change an isoelectric point of SEQ ID NO: 17. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises an amino acid substitution of glutamine (Q) with glutamic acid, or glutamic acid (E). In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises an amino acid substitution of glutamine (Q) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme with glutamic acid (E). In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least one amino acid substitution of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least two amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least three amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises at least four amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residue 1, 6, 43, 82, or 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the amino acid mutation of VH2 that changes an isoelectric point of SEQ ID NO: 17 comprises five amino acid substitutions of glutamine (Q) with glutamic acid (E) at amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17 according to the Kabat numbering scheme. In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 with the Q to R mutations at each of amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17. In some embodiments, the VH2 comprises an amino acid sequence of SEQ ID NO: 17 and an amino acid substitution of glutamine (Q) at each of amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17 according to the Kabat numbering scheme with glutamic acid (E).

[0120] In some embodiments, the antibody or antigen-binding fragment thereof further comprises a fragment crystaUizable (Fc) region. In some embodiments, the antibody or antigen-binding fragment thereof furtherWSGR Docket No. 69143-712.601 comprises a fragment antigen-binding (Fab) region. In some embodiments, the antibody or antigen-binding fragment thereof further comprises two Fab regions. In some embodiments, the first polypeptide associates with the third polypeptide to form a first Fab region and the second polypeptide associates with the fourth polypeptide to form a second Fab region. In some embodiments, the first Fab region binds to CD20 and CD3. In some embodiments, the second Fab region binds to CD20 and CD3. In some embodiments, the first Fab region binds to CD20 and CD3 and the second Fab region binds to CD20 and CD3. In some embodiments, the first polypeptide comprises a first heavy chain constant region 3 (CH3) comprising a first amino acid mutation with reference to a wildtype CH3 sequence. In some embodiments, the first amino acid mutation results in a protrusion in the first polypeptide that is positioned in a cavity in the second polypeptide. In some embodiments, the first amino acid mutation results in a cavity in the first polypeptide that is positioned in a protrusion in the second polypeptide. In some embodiments, the first amino acid mutation comprises a substitution of amino acid residue 354 according to EU numbering with a bulky hydrophobic amino acid. In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), phenylalanine (F), or tryptophan (W). In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), or S354Y mutation. In some embodiments, the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with phenylalanine (F), or S354F mutation. In some embodiment^ the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tryptophan (W), or S354W mutation. In some embodiments, the first amino acid mutation further comprises a substitution of amino acid residue 366 according to EU numbering with a bulky hydrophobic amino acid. In some embodiments, the first amino acid mutation comprises the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y), or T366Y mutation. In some embodiments, the first heavy chain CH3 comprises a lysine (K) at amino acid residue 360 according to EU numbering. In some embodiments, the second polypeptide comprises a second heavy chain CH3 comprising a second amino acid mutation with reference to a wildtype CH3 sequence. In some embodiments, the second amino acid mutation results in a protrusion in the second polypeptide that is positioned in a cavity in the first polypeptide. In some embodiments, the second amino acid mutation results in a cavity in the second polypeptide that is positioned in a protrusion in the first polypeptide. In some embodiments, the second amino acid mutation comprises a substitution of amino acid residue 347 according to EU numbering with an amino acid of negative charge. In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E) or aspartic acid (D). In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E), or Q347E mutation. In some embodiments, the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with aspartic acid (D), or Q347D mutation. In some embodiments, the second amino acid mutation further comprises a substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T), or Y407T mutation. In some embodiments, the VH1 of the first polypeptide or VH2 of the second polypeptide comprises atWSGR Docket No. 69143-712.601 least one amino acid mutation that alters an isoelectric point of the antibody or antigen-binding fragment thereof In some embodiments, (a) the first heavy chain CH3 comprises the first amino acid mutation and a lysine (K) at amino acid residue 360 according to EU numbering and the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), or S354Y mutation and the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y), or T366Y mutation and (b) the second heavy chain CH3 comprises the second amino acid mutation comprising the substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E), or Q347E mutation and the substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T), or Y407T mutation. In some embodiments, the engineered ionic bond and hydrophobic interaction described herein may be combined with knob-into-hole (KIH) mutations to promote heterodimer formation In some embodiments, a heteromultimeric proteins described herein comprises the first CH3 domain and the second CH3 domain each comprising a knob-into-hole (KIH) residue. In some embodiments, the knob-into-hole residues comprises T366Y and Y407T. In some embodiments, the first CH3 domain comprises T366Y and S354Y, and the second CH3 domain comprises Y407T and Q347E. In some embodiments, the first CH3 domain comprises Y407T and S354Y, and the second CH3 domain comprises T366Y and Q347E. In some embodiments, the antibody disclosed herein comprises the first polypeptide and / or the second polypeptide each comprising a heavy chain constant domain 2 (CH2). In sonic embodiments, the heteromultimeric antibody comprises an IgG Fc region. In some embodiments, the IgG Fc region comprises an IgGl, IgG2, IgG3, or IgG4 Fc region. In some embodiments, the first polypeptide is an antibody heavy chain, and / or the second polypeptideis an antibody heavy chain. In some embodiments, the heteromultimeric antibody comprises one or more antibody light chains.

[0121] In some embodiments, the antibody disclosed herein comprises: (a) a first heavy chain comprising from the N-terminus to the C-terminus: a first heavy chain variable domain (VH1), a first heavy chain constant domain 1 (CHI), a first heavy chain constant domain 2 (CH2), and the first CH3 domain; (b) a first light chain comprising from the N-terminus to the C-terminus: a first light chain variable domain (VL1), and a first light chain constant domain (CL); (c) a second heavy chain comprising from the N-terminus to the C-terminus: a second heavy chain variable domain (VH2); a second CHI; a second CH2, and the second CH3 domain; and (d) a second light chain comprising from the N-terminus to the C-terminus: a second light chain variable domain (VL2), and a second CL; wherein VH1 and VL1 associate to form a first antigen binding site that specifically binds to a first target, and VH2 and VL2 associate to form a second antigen binding site that specifically binds to a second target. In some embodiments, VL1 and VL2 have the same amino acid sequence. In some embodiment^ VL1 and VL2 have different amino acid sequences. In some embodiments, the first target and the second target are the same epitopes. In some embodiments, the first target and the second target are different epitopes of the same antigen. In some embodiments, the first target and the second target are different antigens. In some embodiments, the first antigen binding site specifically binds CD20 and the second antigen binding site specifically binds CD3, or the first antigen binding site specifically hinds CD3 and the second antigen binding site specifically binds CD20.WSGR Docket No. 69143-712.601

[0122] In some embodiments, the VH1 comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 10, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VH1 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 10. In some embodiment^ the VH1 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO:10. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 10. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10. In some embodiments, the VH2 comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 11, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VH2 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO:11. In some embodiments, the VH2 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11. In some embodiments, the VH2 comprises the amino acid sequence of SEQ ID NO: 11. In some embodiments, the VL1 comprises an amino add sequence with about 70% to about 100% sequence identity to SEQ ID NO: 12, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VL1 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 75% sequence identity to SEQ IDNO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino addWSGR Docket No. 69143-712.601 sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the VL1 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino add sequence with about 70% to about 100% sequence identity to SEQ ID NO: 12, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the VL2 comprises an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 75% sequence identity to SEQ IDNO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino add sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino add sequence with at least 80% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 12; and the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino add sequence with at least 90% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at leastWSGR Docket No. 69143-712.60190% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11; the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12; or the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiment^ the VH1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 10; the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 11 ; the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12; and the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10; the VH2 comprises the amino acid sequence of SEQ ID NO: 11; the VL1 comprises the amino acid sequence of SEQ ID NO: 12; or the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH1 comprises the amino acid sequence of SEQ ID NO: 10; the VH2 comprises the amino acid sequence of SEQ ID NO: 11; the VL1 comprises the amino acid sequence of SEQ ID NO: 12; and the VL2 comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the first polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 13, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the second polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 14, e.g., about 70%, 71 %, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the third polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQIDNO: 15, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the fourth polypeptide comprises an amino acid sequence with about 70% to about 100% sequence identity to SEQ ID NO: 15, e.g., about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or about 100% sequence identity, or any percentage therebetween. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 80%WSGR Docket No. 69143-712.601 sequence identity to SEQIDNO: 13; the second polypeptide comprises an amino acid sequence withat least 80% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ IDNO: 13; the second polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15; and the fourth polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 13; the second polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 14; the third polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15; or the fourth polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15. In some embodiments, the first polypeptide comprises an amino acid sequence with at least 95% sequence iden...

Claims

WSGR Docket No. 69143-712.601CLAIMSWHAT IS CLAIMED IS:

1. A method of treating an immune or inflammatory disease, comprising administering to a subject in need thereof a therapeutically effective amount of an antibody or antigen-binding fragment thereof that binds to CD20 and CD3, thereby treating the immune or inflammatory disease.2 The method of claim 1, wherein the antibody or antigen -binding fragment thereof comprises:(a) a first polypeptide comprising a first heavy chain variable region (VH1) comprising complementarity determining region (CDR1) 1, CDR2, and CDR3, wherein the VH1-CDR1 comprises the amino acid sequence of SEQ ID NO: 1, the VH1-CDR2 comprises the amino acid sequence of SEQ ID NO: 2, and the VH1-CDR3 comprises the amino acid sequence of SEQ ID NO: 3;(b) a second polypeptide comprising a second heavy chain variable region (VH2) comprising CDR1, CDR2, and CDR3, wherein the VH2-CDR1 comprises the amino acid sequence of SEQ ID NO: 4, the VH2-CDR2 comprises the amino acid sequence of SEQ ID NO: 5, and the VH2- CDR3 comprises the amino acid sequence of SEQ ID NO: 6;(c) a third polypeptide comprising a first light chain variable region (VL1) comprising CDR1, CDR2, and CDR3, wherein the VL1-CDR1 comprises the amino acid sequence of SEQ ID NO: 7, the VL1-CDR2 comprises the amino acid sequence of SEQ ID NO: 8, and the VL1-CDR3 comprises the amino acid sequence of SEQ ID NO: 9; and(d) a fourth polypeptide comprising a second light chain variable region (VL2) comprising CDR1, CDR2, and CDR3, wherein the VL2-CDR1 comprises the amino acid sequence of SEQ ID NO: 7, the VL2-CDR2 comprises the amino acid sequence of SEQ ID NO: 8, and the VL2-CDR3 comprises the amino acid sequence of SEQ ID NO: 9.3 The method of claim 2, wherein the antibody or antigen-binding fragment thereof further comprises a fragment crystatiizable (Fc) region.4 The method of claim 2, wherein the antibody or antigen-binding fragment thereof further comprises a fragment antigen-binding (Fab) region.5 The method of claim 2, wherein the antibody or antigen-binding fragment thereof further comprises two Fab regions.6 The method of claim 2, wherein the first polypeptide associates with the third polypeptide to form a first Fab region and the second polypeptide associates with the fourth polypeptide to form a second Fab region.7 The method of claim 2, wherein the first polypeptide comprises a first heavy chain constant region 3 (CH3) comprising a first amino acid mutation with reference to a wildtype CH3 sequence, wherein:WSGR Docket No. 69143-712.601(a) the first amino acid mutation results in a protrusion in the first polypeptide that is positioned in a cavity in the second polypeptide; or(b) the first amino acid mutation results in a cavity in the first polypeptide that is positioned in a protrusion in the second polypeptide.

8. The method of claim 7, wherein the first amino acid mutation comprises a substitution of amino acid residue 354 according to EU numbering with a bulky hydrophobic amino acid.9 The method of claim 7, wherein the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y), phenylalanine (F), or tryptophan (W).10 The method of claim 7, wherein the first amino acid mutation comprises the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y).11 The method of claim 7, wherein the first amino acid mutation further comprises a substitution of amino acid residue 366 according to EU numbering with a bulky hydrophobic amino acid.12 The method of claim 7, wherein the first amino acid mutation comprises the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y).13 The method of claim 7, wherein the first heavy chain CH3 comprises a lysine (K) at amino acid residue 360 according to EU numbering.14 The method of claim 7, wherein the second polypeptide comprises a second heavy chain CH3 comprising a second amino acid mutation with reference to a wildtype CH3 sequence, wherein:(a) the second amino acid mutation results in a protrusion in the second polypeptide that is positioned in a cavity in the first polypeptide; or(b) the second amino acid mutation results in a cavity in the second polypeptide that is positioned in a protrusion in the first polypeptide.15 The method of claim 14, wherein the second amino acid mutation comprises a substitution of amino acid residue 347 according to EU numbering with an amino acid of negative charge.16 The method of claim 14, wherein the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E) or aspartic acid (D).17 The method of claim 14, wherein the second amino acid mutation comprises a substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E).18 The method of claim 14, wherein the second amino acid mutation further comprises a substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T).19 The method of claim 14, wherein the VH1 or VH2 comprises at least one amino acid mutation that alters an isoelectric point of the antibody or antigen-binding fragment thereof.WSGR Docket No. 69143-712.60120. The method of claim 14, wherein the VH1 comprises an amino acid sequence of SEQ ID NO: 16 and an amino acid substitution of threonine (T) at amino acid residue 83 of SEQ ID NO: 16 according to the Kabat numbering scheme with arginine (R).

21. The method of claim 14, wherein the VH2 comprises an amino acid sequence of SEQ ID NO: 17 and an amino acid substitution of glutamine (Q) at each of amino acid residues 1, 6, 43, 82, and 111 of SEQ ID NO: 17 according to the Kabat numbering scheme with glutamic acid (E).

22. The method of claim 14, wherein:(a) the first heavy chain CH3 comprises the first amino acid mutation and a lysine (K) at amino acid residue 360 according to EU numbering, wherein the first amino acid mutation comprises: the substitution of serine (S) at amino acid residue 354 according to EU numbering with tyrosine (Y); and the substitution of threonine (T) at amino acid residue 366 according to EU numbering with tyrosine (Y); and(b) the second heavy chain CH3 comprises the second amino acid mutation comprising: the substitution of glutamine (Q) at amino acid residue 347 according to EU numbering with glutamic acid (E); and the substitution of tyrosine (Y) at amino acid residue 407 according to EU numbering with threonine (T).

23. The method of claim 2, wherein:(a) the VH1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 10;(b) the VH2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: H;(c) the VL1 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12; or(d) the VL2 comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 12.

24. The method of claim 2, wherein:(a) the VH1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 10;(b) the VH2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: H;WSGR Docket No. 69143-712.601(c) the VL1 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12; or(d) the VL2 comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 12.

25. The method of claim 2, wherein:(a) the VH1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 10;(b) the VH2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: H;(c) the VL1 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12; or(d) the VL2 comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 12.

26. The method of claim 2, wherein:(a) the VH1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 10;(b) the VH2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: H;(c) the VL1 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12; or(d) the VL2 comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 12.

27. The method of claim 2, wherein:(a) the VH1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 10;(b) the VH2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: H;(c) the VL1 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12; or(d) the VL2 comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 12.

28. The method of claim 2, wherein:WSGR Docket No. 69143-712.601(a) the VH1 comprises the amino acid sequence of SEQ ID NO: 10;(b) the VH2 comprises the amino acid sequence of SEQ ID NO: 11;(c) the VL1 comprises the amino acid sequence of SEQ ID NO: 12; or(d) the VL2 comprises the amino acid sequence of SEQ ID NO: 12.

29. The method of claim 2, wherein:(a) the VH1 comprises the amino acid sequence of SEQ ID NO: 10;(b) the VH2 comprises the amino acid sequence of SEQ ID NO: 11;(c) the VL1 comprises the amino acid sequence of SEQ ID NO: 12; and(d) the VL2 comprises the amino acid sequence of SEQ ID NO: 12.

30. The method of claim 2, wherein:(a) the first polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 13;(b) the second polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 14;(c) the third polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15; or(d) the fourth polypeptide comprises an amino acid sequence with at least 80% sequence identity to SEQ ID NO: 15.

31. The method of claim 2, wherein:(a) the first polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 13;(b) the second polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 14;(c) the third polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15; or(d) the fourth polypeptide comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 15.

32. The method of claim 2, wherein:(a) the first polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 13;WSGR Docket No. 69143-712.601(b) the second polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 14;(c) the third polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15; or(d) the fourth polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 15.

33. The method of claim 2, wherein:(a) the first polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 13;(b) the second polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 14;(c) the third polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15; or(d) the fourth polypeptide comprises an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 15.

34. The method of claim 2, wherein:(a) the first polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 13;(b) the second polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 14;(c) the third polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15; or(d) the fourth polypeptide comprises an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 15.

35. The method of claim 2, wherein:(a) the first polypeptide comprises the amino acid sequence of SEQ ID NO: 13;(b) the second polypeptide comprises the amino acid sequence of SEQ ID NO: 14;(c) the third polypeptide comprises the amino acid sequence of SEQ ID NO: 15; or(d) the fourth polypeptide comprises the amino acid sequence of SEQ ID NO: 15.

36. The method of claim 2, wherein:(a) the first polypeptide comprises the amino acid sequence of SEQ ID NO: 13;WSGR Docket No. 69143-712.601(b) the second polypeptide comprises the amino acid sequence of SEQ ID NO: 14;(c) the third polypeptide comprises the amino acid sequence of SEQ ID NO: 15; and(d) the fourth polypeptide comprises the amino acid sequence of SEQ ID NO: 15.

37. The method of claim 1, wherein the immune or inflammatory disease is mediated by a B cell, a plasmablast, or a plasma cell.

38. The method of claim 1, wherein the immune or inflammatory disease is mediated by a mature B cell, a memory B cell, or an activated B cell.

39. The method of claim 1, wherein the immune or inflammatory disease is mediated by an autoantibody.

40. The method of claim 1, wherein the immune or inflammatory disease comprises an autoimmune disease.

41. The method of claim 1, wherein the immune or inflammatory disease comprises allergy, antibody - mediated rejection, alloantibodies, a disease related to or mediated by an alloantibody, amyloidosis, anti-glomerular basement membrane (GBM) (Goodpasture Syndrome), anti-N-methyl-D-aspartate receptor (NMD A) encephalitis (anti -NMD A-R Encephalitis), anti -neutrophil cytoplasmic autoantibody- associated vasculitis (ANCA vasculitis), antiphospholipid antibody syndrome, antisynthetase Syndrome, atopic dermatitis, autoimmune hepatitis, autoimmune necrotizing myopathy,Behcet’s disease, Bullous Pemphigoid, Celiac disease, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), connective tissue disease- associated interstitial lung disease (CTD-ILD), Crohn’s disease, dilated cardiomyopathy, Graves, Guillain Barre Syndrome, Hi dradenitis Suppurativa, idiopathic pulmonary fibrosis (IPF), IgA Nephropathy, Immunoglobulin G4-related disease (IgG4-RD), immune vasculitis (IgA), immune thrombocytopenia (ITP), interstitial lung disease (ILD), Long COVID, Lupus Nephritis, Membranous Nephropathy, microscopic polyangiitis, multiple sclerosis (MS) - primary progressive multiple sclerosis (MS-PPMS), multiple sclerosis (MS) -relapsing-remitting multiple sclerosis (MS-RRMS), myasthenia gravis (MG), myositis-dermatomyositis, myositis-inclusion body, myositis-polymyositis, myositis- immune-mediated necrotizing myositis, neuromyelitis optica spectrum disorder (NMOSD), Pemphigus Vulgaris, polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome, Postural Orthostatic Tachycardia Syndrome (POTS), Polyarteritis Nodosa, Primary Bihary Cirrhosis, Primary Sclerosing Cholangitis, Psoriasis, Psoriatic Arthritis, Raynaud’s Syndrome, Reactive Arthritis, rheumatoid arthritis, scleroderma or systemic sclerosis, Sjogren’s Syndrome, Stiff Person Syndrome, Systemic lupus, Systemic lupus erythematosus (SLE), lupus, Type 1 diabetes, Thyroid eye disease, tumor progression, or ulcerative colitis.

42. The method of claim 1, wherein the immune or inflammatory disease comprises allergic rhinitis or hay fever, allergic rhinoconjunctivitis, allergic asthma, food allergy, drug allergy, insect sting allergy, urticaria, anaphylaxis, allergic bronchopulmonary aspergillosis (ABPA), allergic fungal sinusitis, atopic dermatitis or eczema, eosinophilic esophagitis, or eosinophilic gastroenteritisWSGR Docket No. 69143-712.60143. The method of claim 1, wherein the immune or inflammatory disease comprises peanut allergy, shellfish allergy, milk allergy, egg allergy, IgEtype drug allergy, bee sting allergy, wasp sting allergy, fire ant venom allergy, chronic spontaneous urticaria, or chronic inducible urticaria.

44. The method of claim 1, wherein the immune or inflammatory disease comprises penicillin anaphylaxis.

45. The method of claim 1, wherein the immune or inflammatory disease is mediated by rheumatoid factor (RF) or anti-citrullinated protein antibodies (ACPA).

46. The method of claim 1, wherein the immune or inflammatory disease comprises rheumatoid arthritis.

47. The method of claim 1, wherein the immune or inflammatory disease comprises seropositive rheumatoid arthritis.

48. The method of claim 1, wherein the immune or inflammatory disease comprises systemic lupus erythematosus (SLE).

49. The method of claim 1, wherein the immune or inflammatory disease comprises seropositive systemic lupus erythematosus.

50. The method of claim 1, wherein the immune or inflammatory disease comprises refractory seropositive systemic lupus erythematosus.

51. The method of claim 1, wherein the administering results in a reduction, elimination, inhibition, or depletion of an immune cell or autoantibody.

52. The method of claim 1, wherein the administering results in a reduction, elimination, inhibition, or depletion of an immune cell or autoantibody in serum.

53. The method of claim 1, wherein the administering results in a rapid and persistent reduction, elimination, inhibition, or depletion of an immune cell or autoantibody in serum.

54. The method of claim 51, wherein the eliminating, inhibiting, reducing, or depleting the immune cell comprises resulting in a reduction of the immune cell by about 20% to about 100%.

55. The method of claim 51, wherein the eliminating, inhibiting, reducing, or depleting the immune cell comprises resulting in a reduction of an autoantibody by about 20% to about 100%.

56. The method of claim 51, wherein the eliminating, inhibiting, reducing, or depleting the immune cell comprises resulting in a reduction of the immune cell by about 20% to about 100% in blood or bone marrow.

57. The method of claim 1, wherein the administering results in an increase in the expression of an activation biomarker in T cells.

58. The method of claim 57, wherein the activation biomarker comprises CD69.WSGR Docket No. 69143-712.60159. The method of claim 1, wherein the administering results in the increase in the expression of CD69 in CD4 T cells or CD8 T cells.

60. The method of claim 1, wherein the administering results in an increase of a cytokine.

61. The method of claim 60, wherein the cytokine comprises interferon gamma (IFN-y).

62. The method of claim 1 , wherein the administering results in the reduction, elimination, inhibition, or depletion of the immune cell or autoantibody, the increase in the expression of the activation biomarker in T cells, and an increase of the cytokine.

63. The method of claim 62, wherein the antibody or antigen-binding fragment thereof has an half-maximal effective concentration (ECso) for the reduction, elimination, inhibition, or depletion of the immune cell or autoantibody, the increase in the expression of the activation biomarker in T cells, or the increase of the cytokine, wherein the ECso value of the subject is the same as or similar to the ECso value of a healthy individual.

64. The method of claim 63, wherein the ECso value of the subject with rheumatoid arthritis or systemic lupus erythematosus (SLE) is the same as or similar to the ECso value of the healthy individual.

65. The method of claim 1, wherein the immune or inflammatory disease comprises systemic lupus erythematosus (SLE), wherein the administering results in the reduction, elimination, inhibition, or depletion of:(a) tissue B cells, autoantibodies, immunoglobulins, and / or tissue immune deposits; or(b) B cells in spleen, double- stranded DNA (dsDNA) in serum, total immunoglobulin G (IgG) in serum, and / or IgG deposits in kidney.

66. The method of claim 65, wherein the administering results in a 90% reduction of dsDNA in serum.

67. The method of claim 65, wherein the reduction, elimination, inhibition, or depletion starts within 7 days after the administering.

68. The method of claim 65, wherein the reduction, elimination, inhibition, or depletion lasts for at least 14 days after the administering.

69. The method of claim 52, wherein the immune cell comprises a B cell, a plasmablast, or a plasma cell.

70. The method of claim 52, wherein the immune cell comprises a mature B cell, a memory B cell, or an activated B cell.

71. The method of claim 1, comprising administering to the subject a pharmaceutical composition comprising the antibody or antigen-binding fragment thereof.

72. The method of claim 71, wherein the pharmaceutical composition comprises a buffer, a stabilizing agent, or a surfactant.WSGR Docket No. 69143-712.60173. The method of claim 72, wherein the buffer is in an amount of about 3 mg / ml to about 4 mg / ml.

74. The method of claim 72, wherein the stabilizing agent is in an amount of about 25 mg / ml to about 35 mg / ml.

75. The method of claim 72, wherein the surfactant is in an amount of about 0.1 mg / ml to about 0.3 mg / ml.

76. The method of claim 72, wherein:(a) the buffer comprises L-histidine or L-histidine monohydrochloride;(b) the stabilizing agent comprises arginine hydrochloride or methionine; or(c) the surfactant comprises a polysorbate.

77. The method of claim 72, wherein:(a) the buffer comprises L-histidine and L-histidine monohydrochloride;(b) the stabilizing agent comprises arginine hydrochloride and methionine; and(c) the surfactant comprises a polysorbate.

78. The method of claim 72, wherein the polysorbate comprises polysorbate 20 or polysorbate 80.

79. The method of claim 72, wherein:(a) the buffer is in an amount of about 3.5 mg / ml to about 3.6 mg / ml;(b) the stabilizing agent is in an amount of about 31 mg / ml; and(c) the surfactant is in an amount of about 0.2 mg / ml.

80. The method of claim 72, wherein the pharmaceutical composition comprises:(a) L-histidine in an amount of about 1.9 mg / ml to about 1.95 mg / ml and L-histidine monohydrochloride in an amount of about 1.6 mg / ml to about 1.65 mg / ml;(b) arginine hydrochloride in an amount of about 29 mg / ml to about 30 mg / ml and methionine in an amount of about 1.5 mg / ml; and(c) polysorbate 20 in an amount of about 0.2 mg / ml.

81. The method of claim 72, wherein the pharmaceutical composition comprises about 20 mg / ml of the antibody or antigen-binding fragment thereof.

82. The method of claim 1, wherein the administering comprises administering a first dose of the antibody or antigen-binding fragment thereof.

83. The method of claim 82, further comprising administering to the subj ect a target dose of the antibody or antigen-binding fragment thereof, wherein the target dose is administered after the first dose, wherein the target dose is the same as or higher than the first dose.WSGR Docket No. 69143-712.60184. The method of claim 83, further comprising administering to the subject a second dose of the antibody or antigen-binding fragment thereof, wherein the second dose is administered between the first dose and the target dose, wherein the second dose is the same as or higher than the first dose and the target dose is the same as or higher than the second dose.

85. The method of claim 84, further comprising administering to the subj ect a third dose of the antibody or antigen-binding fragment thereof, wherein the third dose is administered between the second dose and the target dose, wherein the third dose is the same as or higher than the second dose and the target dose is the same as or higher than the third dose.

86. The method of claim 85, further comprising administering to the subject a fourth dose of the antibody or antigen-binding fragment thereof, wherein the fourth dose is administered between the third dose and the target dose, wherein the fourth dose is the same as or higher than the third dose and the target dose is the same as or higher than the fourth dose.

87. The method of claim 86, wherein the first, second, third, fourth, or target dose comprises about 1 mg to about 100 mg of the antibody or antigen-binding fragment thereof.

88. The method of claim 82, wherein the first dose comprises about 1 mg to about 3 mg of the antibody or antigen-binding fragment thereof.

89. The method of claim 84, wherein the second dose comprises about 3 mg to about 10 mg of the antibody or antigen-binding fragment thereof.

90. The method of claim 86, wherein the third, fourth, or target dose is about 3 mg to about 100 mg of the antibody or antigen-binding fragment thereof.

91. The method of claim 82, wherein the first dose is about 1 mg.

92. The method of claim 82, wherein the first dose is about 2 mg.

93. The method of claim 82, wherein the first dose is about 3 mg.

94. The method of claim 84, wherein the second dose is about 3 mg.

95. The method of claim 84, wherein the second dose is about 4 mg.

96. The method of claim 84, wherein the second dose is about 5 mg.

97. The method of claim 84, wherein the second dose is about 6 mg.

98. The method of claim 84, wherein the second dose is about 7 mg.

99. The method of claim 84, wherein the second dose is about 8 mg.

100. The method of claim 84, wherein the second dose is about 9 mg.

101. The method of claim 84, wherein the second dose is about 10 mg.

102. The method of claim 86, wherein the third, fourth, or target dose is about 3 mg.WSGR Docket No. 69143-712.601103. The method of claim 86, wherein the third, fourth, or target dose is about 4 mg.

104. The method of claim 86, wherein the third, fourth, or target dose is about 5 mg.

105. The method of claim 86, wherein the third, fourth, or target dose is about 6 mg.

106. The method of claim 86, wherein the third, fourth, or target dose is about 7 mg.

107. The method of claim 86, wherein the third, fourth, or target dose is about 8 mg.

108. The method of claim 86, wherein the third, fourth, or target dose is about 9 mg.

109. The method of claim 86, wherein the third, fourth, or target dose is about 10 mg.

110. The method of claim 86, wherein the third, fourth, or target dose is about 20 mg.

111. The method of claim 86, wherein the third, fourth, or target dose is about 30 mg.

112. The method of claim 86, wherein the third, fourth, or target dose is about 40 mg.

113. The method of claim 86, wherein the third, fourth, or target dose is about 50 mg.

114. The method of claim 86, wherein the third, fourth, or target dose is about 60 mg.

115. The method of claim 86, wherein the third, fourth, or target dose is about 70 mg.

116. The method of claim 86, wherein the third, fourth, or target dose is about 80 mg.

117. The method of claim 86, wherein the third, fourth, or target dose is about 90 mg.

118. The method of claim 86, wherein the third, fourth, or target dose is about 100 mg.

119. The method of claim 83, wherein the first dose and the target dose are about 1 mg and about 3 mg, respectively.

120. The method of claim 83, wherein the first dose and the target dose are about 3 mg and about 10 mg, respectively.

121. The method of claim 84, wherein the first dose, the second dose, and the target dose are about 3 mg, about 10 mg, and about 10 mg, respectively.

122. The method of claim 84, wherein the first dose, the second dose, and the target dose are about 3 mg, about 10 mg, and about 30 mg, respectively.

123. The method of claim 84, wherein the first dose, the second dose, and the target dose are about 3 mg, about 10 mg, and about 60 mg, respectively.

124. The method of claim 84, wherein the first dose, the second dose, and the target dose are about 3 mg, about 10 mg, and about 100 mg, respectively.

125. The method of claim 86, wherein two doses of the antibody or antigen-binding fragment thereof are administered at least 7 days apart.WSGR Docket No. 69143-712.601126. The method of claim 1, wherein the antibody or antigen-binding fragment thereof is administered on a weekly basis.

127. The method of claim 1, wherein the antibody or antigen-binding fragment thereof is administered once every 10 days.

128. The method of claim 1, wherein the antibody or antigen-binding fragment thereof is administered once every 2 weeks.

129. The method of claim 1, wherein the antibody or antigen-binding fragment thereof is administered once every 3 weeks.

130. The method of claim 1, wherein the antibody or antigen-binding fragment thereof is administered once every 4 weeks.

131. The method of claim 1, wherein the antibody or antigen-binding fragment thereof is administered at most 5 times in 29 days.

132. The method of claim 83, wherein the first dose is about 1 mg and the target dose is about 3 mg, wherein the first dose and the target dose are administered on day 1 and day 8, respectively.

133. The method of claim 83, wherein the first dose is about 3 mg and the target dose is about 10 mg, wherein the first dose and the target dose are administered on day 1 and day 8, respectively.

134. The method of claim 84, wherein the first dose is about 3 mg, the second dose is about 10 mg and the target dose is about 10 mg, wherein the first dose, the second dose and the target dose are administered on day 1, day 8, and day 15, respectively.

135. The method of claim 84, wherein the first dose is about 3 mg, the second dose is about 10 mg and the target dose is about 30 mg, wherein the first dose, the second dose and the target dose are administered on day 1, day 8, and day 15, respectively.

136. The method of claim 84, wherein the first dose is about 3 mg, the second dose is about 10 mg and the target dose is about 60 mg, wherein the first dose, the second dose and the target dose are administered on day 1, day 8, and day 15, respectively.

137. The method of claim 84, wherein the first dose is about 3 mg, the second dose is about 10 mg and the target dose is about 100 mg, wherein the first dose, the second dose and the target dose are administered on day 1, day 8, and day 15, respectively.

138. The method of claim 83, wherein the target dose is administered at least twice, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, or at least 10 times.

139. The method of claim 83, wherein the target dose is administered once every week, once every 2 weeks, once every 3 weeks, once every 4 weeks, or once in more than 4 weeks.WSGR Docket No. 69143-712.601140. The method of claim 1, wherein a dose of the antibody or antigen-binding fragment thereof is administered on day 22 or day 29.

141. The method of claim 82, wherein the target dose is administered on day 22 or day 29.

142. The method of claim 1, further comprising a treatment cycle comprising at least 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, or at least 6 weeks.

143. The method of claim 1, wherein the therapeutically effective amount of the antibody or antigen-binding fragment thereof is calculated based on a biomarker.

144. The method of claim 143, wherein the biomarker comprises a B cell, a plasmablast, a plasma cell, rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), an autoantibody, or an immunoglobulin (Ig).

145. The method of claim 143, wherein the biomarker comprises a mature B cell, a memory B cell, or an activated B cell.

146. The method of claim 143, wherein the biomarker comprises a free kappa light chain or a free lambda light chain.

147. The method of claim 144, wherein the immunoglobulin comprises IgG, IgA, or IgM.

148. The method of claim 143, wherein the therapeutically effective amount is calculated based on an amount of the biomarker.

149. The method of claim 143, wherein the therapeutically effective amount is calculated based on an amount of the biomarker in blood or bone marrow.

150. The method of claim 143, wherein the therapeutically effective amount results in a reduction of about 20% to about 100% of the biomarker after the administering.

151. The method of claim 143, wherein the therapeutically effective amount is calculated based on a reduction in the amount of the biomarker in the blood or bone marrow after the administering.

152. The method of claim 1, wherein the antibody or antigen-binding fragment thereof is administered intramuscularly, intravenously, or subcutaneously.

153. The method of claim 1, wherein the subject is treated with a therapy for an adverse effect before, during, or after the administering.

154. The method of claim 153, wherein the therapy comprises a corticosteroid, an antihistamine, or an antipyretic.

155. The method of claim 153, wherein the therapy comprises dexamethasone, methylprednisolone, diphenhydramine or an equivalent thereof, or acetaminophen or paracetamol or an equivalent thereof.WSGR Docket No. 69143-712.601156. The method of claim 153, wherein the therapy comprises about 20 mg of dexamethasone, about 80 mg of methylprednisolone, about 50 mg of diphenhydramine or an equivalent thereof, or about 650 mg to about 1 g of acetaminophen or paracetamol or an equivalent thereof.

157. The method of claim 153, wherein the subject is treated with:(a) the corticosteroid through intravenous administration at least 1 hour prior to the administering of the antibody or antigen-binding fragment thereof;(b) the antihistamine through intravenous or intramuscular administration at least 30 min prior to the administering of the antibody or antigen-binding fragment thereof;(c) the antihistamine through oral administration at least 1 h prior to the administering of the antibody or antigen-binding fragment thereof; or(d) the antipyretic through oral administration at least 30 min prior to the administering of the antibody or antigen-binding fragment thereof.

158. The method of claim 1, wherein the administering results in elimination or reduction of a B cell through antibody-dependent cellular cytotoxicity (ADCC).

159. The method of claim 1 , wherein the administering results in elimination of a B cell expressing CD20 or CD19 through antibody-dependent cellular cytotoxicity (ADCC).

160. The method of claim 1 , wherein the administering results in a reduction of about 20% to about 100% of a B cell.

161. The method of claim 1 , wherein the administering results in a reduction of about 20% to about 100% of an autoantibody.

162. The method of claim 1 , wherein the administering results in a reduction of about 20% to about 100% of a B cell in blood or bone marrow.

163. The method of claim 1 , wherein the administering results in a reduction of at least 20% of a B cell or an autoantibody.

164. The method of claim 1 , wherein the administering results in a reduction of at least 30% of a B cell or an autoantibody.

165. The method of claim 1 , wherein the administering results in a reduction of at least 40% of a B cell or an autoantibody.

166. The method of claim 1 , wherein the administering results in a reduction of at least 50% of a B cell or an autoantibody.

167. The method of claim 1 , wherein the administering results in a reduction of at least 60% of a B cell or an autoantibody.WSGR Docket No. 69143-712.601168. The method of claim 1, wherein the administering results in a reduction of at least 70% of a B cell or an autoantibody.

169. The method of claim 1 , wherein the administering results in a reduction of at least 80% of a B cell or an autoantibody.

170. The method of claim 1 , wherein the administering results in a reduction of at least 90% of a B cell or an autoantibody.

171. The method of claim 1 , wherein the administering results in a reduction of about 100% of a B cell or an autoantibody.

172. The method of claim 1, further comprising revaccinating the subject.

173. The method of claim 1, wherein the administering does not result in a significant effect on a T cell.

174. The method of claim 1, wherein the subject is treated with a therapy for neutropenia, anaemia, leukopenia, COVID- 19 infection, hypokalemia, cytokine release syndrome, infection, thrombocytopenia, or an infusion-related reaction, before, during, or after the administering.

175. The method of claim 1, wherein the subject is diagnosed with adult-onset rheumatoid arthritis based on the 2010 American College of Rheumatology (ACR) or European League Against Rheumatism (EULAR) classification criteria at least 3 months prior to the administering.

176. The method of claim 1, wherein the subject is refractory to a prior treatment before the administering, wherein the prior treatment comprises a biologic disease-modifying antirheumatic drug (bDMARD) or a targeted synthetic disease-modifying antirheumatic drug (tsDMARD), wherein the subject exhibits inadequate treatment response, lack of clinical benefit, or poor tolerability after at least 12 weeks of the prior treatment.

177. The method of claim 176, wherein the prior treatment comprises 2 bDMARDs in different mechanism classes, or 1 bDMARD and 1 tsDMARD.

178. The method of claim 176, wherein the prior treatment comprises a tumor necrosis factor (TNF) inhibitor.

179. The method of claim 176, wherein the subject exhibits no intolerance to a prior B cell depletion therapy.

180. The method of claim 1, wherein the subject exhibits moderate to severe active rheumatoid arthritis.

181. The method of claim 1, wherein the subject has at least 6 / 68 tender joints and at least 6 / 66 swollen joints.

182. The method of claim 1, wherein the subject tests positive for rheumatoid factor (RF) or anti- citrullinated protein antibody (ACPA).WSGR Docket No. 69143-712.601183. The method of claim 1, wherein the subject, prior to or during the administering, is treated with methotrexate (MTX), hydroxychloroquine, leflunomide, oral sulfasalazine, azathioprine, my cophenol ate, oral prednisone, a non-steroidal anti-inflammatory drug, folic acid, or folinic acid.

184. The method of claim 1, wherein the subject is not treated with a parenteral corticosteroid prior to the administering.

185. The method of claim 1, wherein the subject has:(a) detectable peripheral B cells in an amount of at least 25 cells / ml;(b) absolute neutrophil count of at least 2.0 x 109 / L;(c) platelet count of at least 100 x 109 / L;(d) hemoglobin level of at least 10.0 g / dL;(e) a lymphocyte count of more than 500 cells / pL;(f) a total leukocyte count of at least 3.0 x 109 / L;(g) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of at least 2 times of the upper limit of normal (ULN); and(h) total bilirubin and alkaline phosphatase levels less than 1.5 time of the ULN, wherein the subj ect has serum direct bilirubin less than 1.5 mg / dL when the subj ect has Gilbert’ s syndrome.

186. The method of claim 1, wherein:(a) the subject does not have a class IV rheumatoid arthritis according to American College of Rheumatology (ACR) revised response criteria;(b) the subject does not have a history of a rheumatologic autoimmune disease other than rheumatoid arthritis;(c) the subject does not have secondary Sjogren’s syndrome;(d) the subject does not have a significant systemic involvement secondary to rheumatoid arthritis;(e) the subject does not have Felty’s syndrome;(f) the subject does not have juvenile idiopathic arthritis or idiopathic arthritis diagnosed before the age of 16 years;(g) the subject does not have psoriatic arthritis;(h) the subject does not have axial spondylarthritis or any other disease associated with inflammatory arthritis;(i) the subject does not have a prior rheumatoid arthritis treatment comprising:WSGR Docket No. 69143-712.601 an anti-CD19 therapy or an anti-CD20 therapy, optionally comprising blinatumomab, obinutuzumab, rituximab, ocrelizumab, or ofatumumab, less than 6 months prior to the administering; a cell depleting therapy, optionally comprising an anti-CD4 therapy, anti-CD5 therapy, or an anti-CD3 therapy, less than 6 months prior to the administering; a JAK inhibitor, a Bruton tyrosine kinase (BTK) inhibitor, or a tyrosine kinase 2 (TYK2) inhibitor, optionally comprising baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, fenebrutinib, deucravacitinib, brepocitinib, ropsacitinib, within 4 weeks prior to the administering; an immunomodulatory bDMARD, optionally comprising adalimumab, golimumab, ustekinumab, secukinumab, tocilizumab, abatacept, etanercept, anakinra, infliximab, certolizumab pegol, IL-6, IL-23, or IL-17, less than 12 weeks or 5 half-lives, prior to the administering; an experimental CAR-T or TCE therapy less than 12 months prior to the administering; a calcineurin inhibitor less than 8 weeks prior to the administering; or a cyclophosphamide less than 24 weeks prior to the administering;(j) the subject is not intolerant to a B cell depleting therapy;(k) the subject does not have progressive multifocal leukoencephalopathy; and(l) the subject does not have stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.

187. The method of claim 1, wherein the antibody or antigen-binding fragment thereof binds to a first target and a second target.

188. The method of claim 187, wherein the first target comprises CD20 and the second target comprises CD3.

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