Methods of treating disease using Anti-CD94 antibodies

Abstract

The present disclosure relates to methods of treating an autoimmune disease or disorder by administering an antibody that specifically binds to human CD94, as well as related uses, kits, and articles of manufacture. In some embodiments, the methods comprise administering the anti-CD94 antibody to an individual in need thereof at one or more doses of 24mg, 80mg, 240mg, or 450mg.

Description

Attorney Docket No. 18654-2001540METHODS OF TREATING DISEASE USING ANTI-CD94 ANTIBODIESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application Serial Nos. 63 / 695,083, filed September 16, 2024; 63 / 705,431, filed October 9, 2024, and 63 / 783,828, filed April 4, 2025, the disclosures of each of which are incorporated herein by reference in their entirety.REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0002] The contents of the electronic sequence listing (186542001540SEQLIST.xml; Size: 65,842 bytes; and Date of Creation: September 10, 2025) are incorporated herein by reference in their entirety.FIELD OF THE INVENTION

[0003] The present disclosure relates to methods of treating an autoimmune disease or disorder by administering an antibody that specifically binds to human CD94, as well as related uses, kits, and articles of manufacture.BACKGROUND OF THE INVENTION

[0004] CD94 (also known as killer cell lectin-like receptor DI, KLRD1) is a type II transmembrane protein expressed on natural killer (NK) cells, gamma-delta T cells, and terminal effector CD8 T cells and correlates with expression of other cytotoxic markers such as granzyme B and interferon gamma (IFNy) (Braud, VM et al. (2003) Trends Immunol. 24(4): 162-164; Arlettaz, L. et al. (2004) Eur. J. Immunol. 34(12):3456-3464; Borrego, F. et al. (2006) Immunol. Res. 35(3):263-278; Turk, L. et al. (2024) Front. Immunol. 15: 1285798; Pitard, V. et al. (2008) Blood 112(4): 1317-1324). CD94 expression is restricted to cytotoxic lymphocytes and is not identified on non-immune cells. Cytotoxic or terminal effector CD8 T cells are thought to play pathological roles in the development of autoimmune diseases, including but not limited to alopecia areata (AA) and vitiligo (VT) (Gleave, A. et al. (2023) Biomolecules 13 (2) : 388 ; Frisoli, M.L. et al. (2020) Annu Rev Immunol. 38:621-648; Xing, L. et al. (2014) Nat. Med. 20(9): 1043- 1049; Lee, E.Y. et al. (2023) Proc Natl Acad Sci USA 120(29):e2305764120; Harris,Invest Dermatol. 132(7): 1869-1876).

[0005] AA and VT are both disfiguring autoimmune skin diseases which share some aspects of their autoimmune character (Rork, J.F. et al. (2016) Curr Opin Pediatr. 28(4):463-469). The autoimmune response in both cases is associated with granzyme B and IFNy production, with IFNy-induced cytokines and CD8+ cytotoxic T cells driving the pathogenic response.

[0006] Lichen planus (LP) is a T cell-mediated disease affecting the stratified squamous epithelia of the skin and / or mucus membrane. Histologically, the disease is characterized by a lichenoid inflammatory infiltrate and vacuolar degeneration of the basal layer of the epidermis. LP has three major subtypes: Cutaneous, mucosal and appendageal LP. Rarely, it may affect the nails in the absence of skin and / or 1MOFO-360690948Attorney Docket No. 18654-2001540 mucosal changes. LP may also be induced by several drugs, typically anti -hypertensive medication or be associated with infections, particularly viral hepatitis. The diagnosis is based on the clinical presentation and characteristic histological findings. Although the disease is often self-limiting, the intractable pruritus and painful mucosal erosions result in significant morbidity. The current first-line treatment are topical and / or systemic corticosteroids. In addition, immunosuppressants may be used as corticosteroid-sparing agents. These, however, are often not sufficient to control disease. Novel treatment therapies are needed.

[0007] Without wishing to be bound to theory, it is thought that CD94 can function as an anchor protein for anti-CD94 antibody treatment to eliminate CD94-expressing cells via antibody-dependent cellular cytotoxicity (ADCC). Antibodies that specifically bind CD94 are under development and clinical investigation; see, e.g.. International Pub. Nos. W02022 / 072508 and WO2023 / 183926 and clinical trial NCT05475925. In non-human primate studies, anti-CD94 antibody treatment via weekly infusion showed depletion of CD94+ CD8 T cells in blood and tissue compartments (spleen, lymph node, gut, and bone marrow).

[0008] As such, targeting cells expressing CD94 may be useful in development of therapies for autoimmune diseases and disorders. Accordingly, there is a need in the art to test the efficacy and safety of targeting CD94 (e.g., using an anti-CD94 antibody) in the treatment of autoimmune diseases.

[0009] All references cited herein, including patent applications and publications, are incorporated by reference in their entirety.SUMMARY OF THE DISCLOSURE

[0010] To meet these and other needs, the present disclosure provides, inter alia, methods of treating an autoimmune disease or disorder in an individual in need thereof by administering an antibody that specifically binds to human CD94, e.g. , at one or more doses of 24mg, 80mg, 240mg, or 450mg. Related compositions, uses, kits, and articles of manufacture are further provided.

[0011] In some aspects, provided herein is a method of treating an autoimmune disease or disorder in an individual in need thereof, the method comprising administering to the individual one or more doses of an antibody that specifically binds to human CD94, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg; wherein the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3, and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6.

[0012] In some embodiments according to any one of the embodiments disclosed herein, the autoimmune disease or disorder is Felty’s syndrome, rheumatoid arthritis (RA), inclusion body myositis, alopecia areata (AA), vitiligo (VT), or lichen planus (LP). In some embodiments, the autoimmune disease or disorder is alopecia areata (AA) or vitiligo (VT). In some embodiments, the AA is moderate to severe2MOFO-360690948Attorney Docket No. 18654-2001540AA. In some embodiments, prior to administration of the antibody to the individual, the individual has a current episode of AA lasting from greater than 6 months to less than 10 years. In some embodiments, the individual does not have diffuse AA. In some embodiments, the VT is non-segmental VT. In some embodiments, the autoimmune disease or disorder is LP. In some embodiments, the LP is cutaneous LP, mucosal LP, appendageal LP, or lichen planopilaris. In some embodiments, the LP is selected from Oral Lichen Planus, Cutaneous Lichen Planus, Esophageal Lichen Planus, Genital Lichen Planus, Lichen Planopilaris, Nail Lichen Planus, Lichen Planus Pigmentosus, Hypertrophic Lichen Planus, Bullous Lichen Planus, and Inverse Lichen Planus.

[0013] In some embodiments according to any one of the embodiments disclosed herein, administration of the antibody to the individual results in a reduction in one or more symptoms of the autoimmune disease or disorder in the individual. In some embodiments, administration of the antibody to the individual results in depletion of CD94+ cells in the individual. In some embodiments, administration of the antibody to the individual results in depletion of CD8+ CD94+ T cells in the individual.

[0014] In some aspects, provided herein is a method of treating an autoimmune disease or disorder in an individual in need thereof, the method comprising administering to the individual one or more doses of an antibody that specifically binds to human CD94, wherein the autoimmune disease or disorder is alopecia areata (AA), vitiligo (VT), or lichen planus (LP). In some embodiments, the individual is a human. In some embodiments, the AA is moderate to severe AA. In some embodiments, the VT is non-segmental VT. In some embodiments, the LP is cutaneous LP, mucosal LP, appendageal LP, or lichen planopilaris. In some embodiments, the LP is selected from Oral Lichen Planus, Cutaneous Lichen Planus, Esophageal Lichen Planus, Genital Lichen Planus, Lichen Planopilaris, Nail Lichen Planus, Lichen Planus Pigmentosus, Hypertrophic Lichen Planus, Bullous Lichen Planus, and Inverse Lichen Planus. Any of the anti-CD94 antibodies described herein may find use in said method. In some embodiments, binding of the antibody to human CD94 does not block binding between human CD94 and human HLA-E, i. e. , the antibody does not block binding between human CD94 and human HLA-E. In some embodiments, the antibody binds human CD94 expressed on the surface of a cell, optionally a human natural killer (NK) cell or a human CD8+ CD94+ T cell. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises a CDR- H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3, and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6. In some embodiments, the VH domain of the antibody comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain of the antibody comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the antibody is a human antibody. In some embodiments, the antibody is a full-length antibody that comprises an Fc region. In some embodiments, the Fc region is a human IgGl Fc region. In some embodiments, the antibody comprises a human Fc region that is non-3MOFO-360690948Attorney Docket No. 18654-2001540 fucosylated. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:65 and a light chain comprising the amino acid sequence of SEQ ID NO:66. In some embodiments, the antibody is a monoclonal, monospecific antibody. In some embodiments, the antibody is dibotatug.

[0015] In some embodiments according to any one of the embodiments disclosed herein, the one or more doses of the antibody is / are administered to the individual as part of a pharmaceutical composition comprising the antibody and one or more pharmaceutically acceptable carriers. In some embodiments, the one or more doses of the antibody is / are administered intravenously to the individual. In some embodiments, the method comprises administering to the individual two or more doses of 24mg, 80mg, 240mg, or 450mg of the antibody at an interval of 1 week or 7 days. In some embodiments, the method comprises administering to the individual two or more doses of 24mg, 80mg, 240mg, or 450mg of the antibody at an interval of 2 weeks or 14 days. In some embodiments, the method comprises administering to the individual two or more doses of 24mg, 80mg, 240mg, or 450mg of the antibody at an interval of 4 weeks or 28 days. In some embodiments, the antibody is administered to the individual on Day 1, Day 8, Day 15, and Week 4. In some embodiments, after Week 4, the antibody is administered to the individual once every 4 weeks. In some embodiments, at least one of the doses of the antibody is administered to the individual intravenously in a first portion of the dose on a first day and the remaining portion of the dose on the next day. In some embodiments, the first dose of the antibody is administered to the individual intravenously in a first portion of the first dose on Day 1 and the remaining portion of the first dose on Day 2. In some embodiments, the first dose of the antibody is administered to the individual intravenously in a first portion of lOmg on Day 1 and the remainder of the first dose on Day 2. In some embodiments, the first portion of the first dose is administered to the individual intravenously over 4 hours on Day 1, and the remainder of the first dose is administered to the individual intravenously over 4 hours on Day 2. In some embodiments, after the first dose, the antibody is administered intravenously to the individual over 2-3 hours. In some embodiments, the antibody is administered intravenously to the individual over 3 hours on Day 8 and Day 15, and over 2 hours on Week 4 and subsequent doses. In some embodiments, the antibody is administered to the individual at a dose of 24mg on Day 1, Day 8, Day 15, Week 4, Week 8, Week 12, Week 16, and Week 20. In some embodiments, the antibody is administered to the individual at a dose of lOmg on Day 1, 14mg on Day 2, 24mg on Day 8, 24mg on Day 15, 24mg on Week 4, 24mg on Week 8, 24mg on Week 12, 24mg on Week 16, and 24mg on Week 20. In some embodiments, the antibody is administered to the individual at a dose of 80mg on Day 1, Day 8, Day 15, Week 4, Week 8, Week 12, Week 16, and Week 20. In some embodiments, the antibody is administered to the individual at a dose of lOmg on Day 1, 70mg on Day 2, 80mg on Day 8, 80mg on Day 15, 80mg on Week 4, 80mg on Week 8, 80mg on Week 12, 80mg on Week 16, and 80mg on Week 20. In some embodiments, the antibody is administered to the individual at a dose of 240mg on Day 1, Day 8, Day 15, Week 4, Week 8, Week 12, Week 16, and Week 20. In some embodiments, the antibody is administered to the individual at a dose of lOmg on Day 1, 230mg on Day 2, 240mg on Day 8, 240mg on Day 15,4MOFO-360690948Attorney Docket No. 18654-2001540240mg on Week 4, 240mg on Week 8, 240mg on Week 12, 240mg on Week 16, and 240mg on Week 20. In some embodiments, the antibody is administered to the individual at a dose of 450mg on Day 1, Day 8, Day 15, Week 4, Week 8, Week 12, Week 16, and Week 20. In some embodiments, the antibody is administered to the individual at a dose of lOmg on Day 1, 440mg on Day 2, 450mg on Day 8, 450mg on Day 15, 450mg on Week 4, 450mg on Week 8, 450mg on Week 12, 450mg on Week 16, and 450mg on Week 20. In some embodiments, the antibody is administered to the individual for up to 6 months. In some embodiments, the method further comprises administering a corticosteroid to the individual prior to one or more doses of the antibody. In some embodiments, the corticosteroid is methylprednisolone. In some embodiments, 80mg methylprednisolone is administered intravenously to the individual at least 60 minutes and no more than 3 hours prior to the first dose of the antibody. In some embodiments, the first dose of the antibody is administered to the individual intravenously in a first portion of the first dose on Day 1 and the remaining portion of the first dose on Day 2, and wherein 80mg methylprednisolone is administered intravenously to the individual at least 60 minutes and no more than 3 hours prior to the first portion of the first dose on Day 1 and at least 60 minutes and no more than 3 hours prior to the remaining portion of the first dose on Day 2. In some embodiments, the method further comprises administering an anti-pyretic to the individual prior to one or more doses of the antibody. In some embodiments, the antipyretic is acetaminophen. In some embodiments, 650-1000mg acetaminophen is administered orally to the individual at least 30 minutes and no more than 3 hours prior to one or more doses of the antibody. In some embodiments, the method further comprises administering an antihistamine to the individual prior to one or more doses of the antibody. In some embodiments, the antihistamine is diphenhydramine. In some embodiments, 50mg diphenhydramine is administered orally to the individual at least 30 minutes and no more than 3 hours prior to one or more doses of the antibody. In some embodiments, the antihistamine is cetirizine. In some embodiments, cetirizine is administered orally to the individual at least 30 minutes and no more than 3 hours prior to one or more doses of the antibody. In some embodiments, the antihistamine is loratadine. In some embodiments, lOmg loratadine is administered orally to the individual at least 30 minutes and no more than 3 hours prior to one or more doses of the antibody.

[0016] In some embodiments according to any one of the embodiments disclosed herein, the VH domain of the antibody comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain of the antibody comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the antibody is a human antibody. In some embodiments, the antibody is a full length antibody that comprises an Fc region. In some embodiments, the Fc region is a human IgGl Fc region. In some embodiments, the antibody comprises a human Fc region that is non-fucosylated. In some embodiments, the antibody is non-fucosylated or afucosylated. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:65 and a light chain comprising the amino acid sequence of SEQ ID NO:66. In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody is a monospecific antibody. In some embodiments, the antibody is a monoclonal, monospecific antibody. In some embodiments, the antibody is a monoclonal, monospecific,5MOFO-360690948Attorney Docket No. 18654-2001540 full length antibody. In some embodiments, the antibody is a monoclonal, monospecific, full length, human antibody. In some embodiments, the antibody is dibotatug.

[0017] In some aspects, provided herein is an antibody that specifically binds to human CD94 for use in a method according to any one of the above embodiments. In some aspects, provided herein is an antibody that specifically binds to human CD94 for use in a method of treating an autoimmune disease or disorder in an individual in need thereof, said method comprising administering the antibody to the individual one or more doses of the antibody, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg; wherein the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3; and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NON, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6. In some aspects, provided herein is an antibody that specifically binds to human CD94 for use in a method of treating an autoimmune disease or disorder in an individual in need thereof, wherein the autoimmune disease or disorder is alopecia areata (AA), vitiligo (VT), or lichen planus (LP). In some embodiments, the LP is cutaneous or oral LP.

[0018] In some aspects, provided herein is the use of an antibody that specifically binds to human CD94 in the manufacture of a medicament for treating an autoimmune disease or disorder in an individual in need thereof, wherein the medicament comprises one or more doses of 24mg, 80mg, 240mg, or 450mg of the antibody. In some embodiments, the medicament is to be administered according to any one of the above embodiments. In some aspects, provided herein is the use of an antibody that specifically binds to human CD94 in the manufacture of a medicament for treating an autoimmune disease or disorder in an individual in need thereof, wherein the autoimmune disease or disorder is alopecia areata (AA), vitiligo (VT), or lichen planus (LP). In some embodiments, the LP is cutaneous or oral LP.

[0019] In some aspects, provided herein is an article of manufacture, comprising a container comprising one or more doses of an antibody that specifically binds to human CD94, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg; wherein the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NON, and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NON, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6. In some embodiments, the container comprises one or more doses of 24mg of the antibody. In some embodiments, the container comprises one or more doses of 80mg of the antibody. In some embodiments, the container comprises one or more doses of 240mg of the antibody. In some embodiments, the container comprises one or more doses of 450mg of the antibody. In6MOFO-360690948Attorney Docket No. 18654-2001540 some embodiments, the article of manufacture is for use in treating an autoimmune disease or disorder, e.g., Felty’s syndrome, rheumatoid arthritis (RA), inclusion body myositis, alopecia areata (AA), vitiligo (VT), or lichen planus (LP). In some embodiments, the LP is cutaneous or oral LP. In some embodiments, the antibody is dibotatug.

[0020] In some aspects, provided herein is a kit, comprising: (a) one or more doses of an antibody that specifically binds to human CD94, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg, wherein the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3; and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6; and (b) a package insert with instructions for administering the antibody to an individual in need thereof at one or more doses selected from 24mg, 80mg, 240mg, and 450mg, e.g., according to any one of the above embodiments. In some embodiments, the kit is for use in treating an autoimmune disease or disorder, e.g., Felty’s syndrome, rheumatoid arthritis (RA), inclusion body myositis, alopecia areata (AA), vitiligo (VT), or lichen planus (LP). In some embodiments, the LP is cutaneous or oral LP. In some aspects, provided herein is a kit, comprising: (a) an antibody that specifically binds to human CD94; and (b) a package insert with instructions for administering the antibody to an individual in need thereof for treatment of alopecia areata (AA), vitiligo (VT), or lichen planus (LP) (e.g., cutaneous or oral LP), e.g., according to any one of the above embodiments.

[0021] In some aspects, there is provided a method of treating an autoimmune disease or disorder in an individual in need thereof, the method comprising administering to the individual one or more doses of dibotatug, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg. In some embodiments, the autoimmune disease or disorder is Felty’s syndrome, rheumatoid arthritis (RA), inclusion body myositis, alopecia areata (AA), vitiligo (VT), or lichen planus (LP) (e.g., oral LP, cutaneous LP, mucosal LP, appendageal LP, or lichen planopilaris).

[0022] In some aspects, there is provided an article of manufacture, comprising a container comprising one or more doses of dibotatug, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg. In some embodiments, the container comprises one or more doses of 24mg of dibotatug. In some embodiments, the container comprises one or more doses of 80mg of dibotatug. In some embodiments, the container comprises one or more doses of 240mg of dibotatug. In some embodiments, the container comprises one or more doses of 450mg of dibotatug. In some embodiments, the container comprises 24mg of dibotatug. In some embodiments, the container comprises 80mg of dibotatug. In some embodiments, the container comprises 240mg of dibotatug. In some embodiments, the container comprises 450mg of dibotatug. In some embodiments, the article of7MOFO-360690948Attorney Docket No. 18654-2001540 manufacture is for use in treating an autoimmune disease or disorder, e.g., Felty’s syndrome, rheumatoid arthritis (RA), inclusion body myositis, alopecia areata (AA), vitiligo (VT), or lichen planus (LP).

[0023] In any of the above aspects, the LP is selected from Oral Lichen Planus, Cutaneous Lichen Planus, Esophageal Lichen Planus, Genital Lichen Planus, Lichen Planopilaris, Nail Lichen Planus, Lichen Planus Pigmentosus, Hypertrophic Lichen Planus, Bullous Lichen Planus, and Inverse Lichen Planus.

[0024] It is to be understood that one, some, or all of the properties of the various embodiments described herein may be combined to form other embodiments of the present disclosure. These and other aspects of the present disclosure will become apparent to one of skill in the art. These and other embodiments of the present disclosure are further described by the detailed description that follows.BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The novel features of the invention are set forth with particularity in the appended claims. A better 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 invention are utilized, and the accompanying drawings of which:

[0026] FIG. 1 shows a trial schema for a 48-week, parallel-group, open-label, randomized Phase lb study to explore the safety and clinical activity of anti-CD94 antibody in adults with alopecia areata (AA) or vitiligo (VT) or lichen planus (LP). For each arm, the first dose of anti-CD94 antibody is administered over 2 days, with lOmg being given on Day 1, and the remainder of the dose given on Day 2. Subjects with alopecia areata and vitiligo and lichen planus are stratified by disease at a ratio of approximately 1 : 1 : 1 : 1 in each arm. The anti-CD94 antibody used in the study is a fully human, IgGl isotype, non- fucosylated antibody that comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:65 and a light chain comprising the amino acid sequence of SEQ ID NO:66. IV: intravenous.

[0027] FIG. 2 shows CD94+CD8+ T cells in peripheral blood of healthy donors and patients with autoimmune diseases. Cryopreserved PBMCs from 18 healthy donors (HD), 1 alopecia areata (AA), 14 rheumatoid arthritis (RA), and 2 vitiligo (VT) patients were procured from BioIVT, Cureline and Stanford Blood Center. CD94+CD8+ T cells were quantified by flow cytometry. Dotted line represents the average value of HDs.

[0028] FIGs. 3A-3D show CD94 expression by immunohistochemistry (IHC) in skin biopsies of lichen planus (LP) patients and healthy donors (HD). Formalin-fixed, paraffin-embedded skin biopsies of LP and HD individuals were procured commercially and stained for CD94 via IHC at Mosaic Laboratories using a proprietary assay. %CD94 (FIG. 3A) and CD94 (FIG. 3B) H-score from the total mononuclear cell population were scored by a board-certified pathologist. Error bars are shown as the standard deviation. Statistical analysis was performed via student’s t-test. Representative H&E and CD94 IHC images of a LP skin biopsy is shown in FIG. 3C. Representative H&E and CD94 IHC images of a HD skin biopsy is shown in FIG. 3D.8MOFO-360690948Attorney Docket No. 18654-2001540DETAILED DESCRIPTION OF THE INVENTION

[0029] AA is an autoimmune disease characterized by non-scarring hair loss of the scalp and other hairbearing areas of the body. A large meta-analysis, including 300 million subjects, estimated the global prevalence of AA as 2.11% of the global population (Lee, H.H. et al. (2020) J Am Acad Dermatol. 82(3):675-682). Until recently there were no US Food and Drug Administration (FDA) -approved treatments for AA, and a variety of approaches were used, including contact irritants, contact immunotherapy, corticosteroids, prostaglandins, vitamin D / analogs, immunosuppressives such as cyclosporine, tacrolimus, azathioprine, methotrexate, minoxidil, antihistamines, hydroxychloroquine, aprimilast, HMG-CoA reductase inhibitors, anti-IL4 / 13 (e.g., duplimumab), anti-IL-17 (e.g., secukinumab), platelet rich plasma, and laser and light therapy (Lepe, K. et al. , PMID 30725685; Sibbald, C. (2023) J Cutan Med Surg. 27(3):241-259). The effectiveness of these treatments varies, especially for severe disease. Recently, two orally administered Janus kinase (JAK) inhibitors have been approved for AA: baricitinib (OLUMIANT™) and ritlecitinib (LITFULO™). Both drugs have black box warnings including serious infections leading to hospitalization, tuberculosis (TB), lymphoma / other malignancies, and thrombosis. In addition, the ritlecitinib warning includes all-cause mortality, major adverse cardiac events, and serious infections leading to death. In the registration studies, the proportion of patients who had >80% scalp hair regrowth was 15 to 16% better at Week 36 in patients who received baricitinib at 2mg / day compared with placebo and 21.4% better at Week 24 for patients who received ritlecitinib at 50mg / day. The safety concerns and efficacy profile of FDA -approved therapies suggest there is still an unmet need in this area. In particular, a targeted biologic immunotherapy such as anti-CD94 antibody may offer a favorable risk / benefit.

[0030] VT is a depigmenting skin disorder resulting from autoimmune loss of melanocytes leading to loss of pigment in the affected areas of the skin (Bergqvist, C. et al. (2020) Dermatology 236(6) :571-592). VT is the most common skin depigmenting disease and affects 0.5 to 2% of the population globally. For stable non-segmental (NSV) disease, topical treatment with corticosteroids or calcineurin inhibitors are used as first-line therapy (Frisoli, M.L. et al. (2020) Annu Rev Immunol. 38:621-648) and typically 2-3 months of therapy are given before response is evaluated. Second-line treatments are phototherapy with narrowband ultraviolet B or psoralen with ultraviolet A and systemic steroids. For rapidly progressing disease, systemic steroids are given. In July 2022 ruxolitinib (JAK1 / 2 inhibitor; OPZELURA™) topical cream was approved for “non-segmental vitiligo in adults and adolescents aged 12 and upward,” originally approved in 2011 for atopic dermatitis. Despite the topical delivery in VT the label carries black box warnings of the risk of serious infections, mortality, and malignancy from the oral delivery forms of the drug. This suggests that there is potential for a targeted biologic immunotherapy, such as anti-CD94 antibody, which may have a favorable risk / benefit profile.

[0031] Cytotoxic or terminal effector CD8 T cells are thought to play pathological roles in the development of autoimmune diseases such as alopecia areata (AA) and vitiligo (VT) (Gleave, A. et al. (2023) Biomolecules 13(2):388; Frisoli, M.L. et al. (2020) Annu Rev Immunol. 38:621-648; Xing, L. et al.9MOFO-360690948Attorney Docket No. 18654-2001540(2014) Nat. Med. 20(9): 1043-1049; Lee, E.Y. et al. (2023) Proc Natl Acad Set USA 120(29):e2305764120; Harris, J. E. et al. (2012) J Invest Dermatol. 132(7): 1869-1876). A body of evidence suggests that these CD8 T cells are elevated by 2- to 3-fold in blood and diseased skin compared to healthy individuals (Lee, E.Y. et al. (2023) Proc Natl Acad Sci USA 120(29):e2305764120; Nigam, P.K. et al. (2011) Indian J Dermatol Venereol Leprol. 77(1): 111). These CD8 T cells are clonally expanded, proximal to the tissue site where damage occurs, and produce granzyme B and IFNy (Gellatly,K.J. et al. (2021) Sci Transl Med. 13(610):eabd8995; de Jong, A. et al. (2018) JCI Insight. 3(19):el21949; Nigam, P.K. et al. (2011) Indian J Dermatol Venereol Leprol. 77(1): 111; Xing, L. et al. (2014) Nat. Med. 20(9): 1043-1049; Turk, L. et al. (2024) Front. Immunol. 15: 1285798; Takahashi, R. et al. (2024) J Invest Dermatol. S0022-202X(24):25-3; van den Boom, J.G. et al. (2009) J Invest Dermatol. 129(9):2220- 2232). These cells are known to be activated upon antigen encounter and play a direct role in destruction of melanocytes and hair follicles in AA and VT (Gleave, A. et al. (2023) Biomolecules 13(2):388; Frisoli, M.L. et al. (2020) Annu Rev Immunol. 38:621-648).

[0032] Cytotoxic CD8+ T cells are thought to be the major producers of IFNy and granzyme B in AA and VT. In vivo studies of IFNy inhibition in AA and VT mouse models demonstrated reversible hair loss and skin re-pigmentation upon IFNy blockade (Harris, J.E. et al. (2012) J Invest Dermatol. 132(7): 1869- 1876; Xing, L. et al. (2014) Nat. Med. 20(9): 1043-1049). Furthermore, responders to Janus kinase (JAK) inhibitors in clinical studies of AA not only experienced hair regrowth 12 weeks post treatment, but also suppression of granzyme B+ CD8 T cells (Xing, L. et al. (2014) Nat. Med. 20(9): 1043-1049). From bulk and single-cell RNA-sequencing studies, CD94 is upregulated by 2.8-fold in lesional skin of AA patients and is significantly increased in blood and lesional skin of VT patients relative to healthy controls (Xing,L. et al. I A) Nat. Med. 20(9): 1043-1049; Gellatly, K.J. et al. (2021) Sci Transl Med.13(610):eabd8995; Subramanya, R.D. et al. (2010) Genomics 96(3): 146-153).

[0033] Taken together, CD94 is highly expressed in AA and VT skin lesions and is positively correlated with granzyme B and IFNy expression on the pathological CD8+ T cells. In addition, given the association between IFNy / granzyme B levels in the skin and disease severity (Koguchi-Yoshioka, H. et al. (2021) J Invest Dermatol. 141(2):427-429.el0; Ng, C.Y. et al. (2022) Front Immunol. 13:872458), CD94 may also contribute to disease severity in AA and VT. These preclinical findings, along with the recent approval of JAK inhibitors in these diseases (OLUMIANT® or baricitinib, LITFULO® or ritlecitinib, OPZELURA® or ruxolitinib) suggest that anti-CD94 antibody treatment has the potential to eliminate pathologic CD8 T cells and may bring clinical benefit in AA and VT patients.

[0034] LP is a chronic, inflammatory disease that can involve the skin, oral mucosa, genitals, nails, esophagus, and other areas. It is difficult to treat with 30-50% being refractory to current therapies (Passeron et al. Br J Dermatol 2024; 00: 1-11), and LP frequently has significant impacts on quality of life, as symptoms associated with LP include intense pruritus and pain. In addition, LP may lead to longterm or permanent effects, depending on the site involved, including scarring and hair loss (for cutaneous forms), nail disfigurement (when nails are involved), and esophageal strictures (for esophageal LP). No 10MOFO-360690948Attorney Docket No. 18654-2001540 well-controlled RCT has demonstrated efficacy, and typical first-line therapy consists of corticosteroids (topical, intralesional, or systemic, depending on the extent and type of LP), but corticosteroids are well- known to cause various toxicities and adverse effects that can be local (e.g., skin atrophy) or systemic (e.g., cataracts, bone density loss, skin changes, susceptibility to infections, etc.). Thus, there is an unmet medical need for safe, more effective therapies.

[0035] As shown by biopsies of active LP lesions (e.g., skin biopsy for cutaneous LP), histopathology is typified by a set of characteristic pathologic findings including a dense lymphocytic infiltrate at the dermal-epidermal junction, and cytotoxic CD8+ T cells directed against basal keratinocytes are thought to play a central role (Lehman et al. Int J Dermatol. 2009;48(7):682). These cytotoxic cells are depleted in circulation and in tissue by DR-01, a novel molecule that is being developed in several indications (vitiligo, alopecia areata, cytotoxic T-cell and NK-cell lymphomas, and LGL leukemia) and has been discovered by the Applicant to be active in cutaneous disease, as demonstrated by its early efficacy in cytotoxic T-cell lymphomas, many of which involve the skin.

[0036] Applicant has discovered that the anti-CD94 antibody dibotatug, also known as DR-01, can safely deplete pathogenic, autoreactive cytotoxic cell types in the skin and other tissues. Based at least in part on this discovery, treatment of LP patients with DR-01 is expected to be safe, effective, and steroid- sparing. The clinical investigation described herein, and, e.g. in Example 1, to demonstrate safety, PK, PD, and preliminary efficacy in LP highlights the utility for DR-01 in the treatment of cutaneous lichen planus and other forms of lichen planus, including, but not limited to, Oral Lichen Planus, Cutaneous Lichen Planus, Esophageal Lichen Planus, Genital Lichen Planus, Lichen Planopilaris, Nail Lichen Planus, Lichen Planus Pigmentosus, Hypertrophic Lichen Planus, Bullous Lichen Planus, and Inverse Lichen Planus. Forms of Lichen Planus are well known in the art, and are reviewed, e.g., in Boch et al. (Boch et al. Lichen Planus. Front Med (Lausanne). 2021 Nov 1 ;8: 737813) and Weston et al. (Int J Womens Dermatol. 2015 Aug; 1(3): 140-149).

[0037] To meet these and other needs, the present disclosure provides, inter alia, methods for treating an autoimmune disease or disorder in an individual (e.g., in need thereof), comprising administering to the individual one or more doses of an antibody that specifically binds to human CD94, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg.

[0038] Further provided herein are articles of manufacture (e.g., for treating an autoimmune disease or disorder), comprising a container comprising one or more doses of an antibody that specifically binds to human CD94, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg.

[0039] Yet further provided herein are kits (e.g., for treating an autoimmune disease or disorder), comprising: (a) one or more doses of an antibody that specifically binds to human CD94, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg; and (b) a package insert with instructions for administering the antibody to an individual in need thereof at one or more doses selected from 24mg, 80mg, 240mg, and 450mg.11MOFO-360690948Attorney Docket No. 18654-2001540

[0040] Several aspects are described below with reference to example applications for illustration. It should be understood that numerous specific details, relationships, and methods are set forth to provide a full understanding of the features described herein. One having ordinary skill in the relevant art, however, will readily recognize that the features described herein can be practiced without one or more of the specific details or with other methods. The features described herein are not limited by the illustrated ordering of acts or events, as some acts can occur in different orders and / or concurrently with other acts or events. Furthermore, not all illustrated acts or events are required to implement a methodology in accordance with the features described herein.I. Definitions

[0041] As used herein, the singular forms “a”, “an”, and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. Furthermore, to the extent that the terms “including”, “includes”, “having”, “has”, “with”, or variants thereof are used in either the detailed description and / or the claims, such terms are intended to be inclusive in a manner similar to the term “comprising”. The term “comprising” as used herein is synonymous with “including” or “containing”, and is inclusive or open-ended.

[0042] Any reference to “or” herein is intended to encompass “and / or” unless otherwise stated. As used herein, the term “about” with reference to a number refers to that number plus or minus 10% of that number. The term “about” with reference to a range refers to that range minus 10% of its lowest value and plus 10% of its greatest value.

[0043] As used herein, the term “antibody” includes monoclonal antibodies (including full length antibodies which have an immunoglobulin Fc region), antibody compositions with polyepitopic specificity, monospecific antibodies, and multispecific antibodies (e.g., bispecific antibodies, diabodies, and single-chain molecules). Antibody “fragments” (e.g., antigen-binding fragments of an antibody of the present disclosure) include Fab, F(ab')2, and Fv fragments.

[0044] The “variable domain” of an antibody or fragment refers to the amino-terminal domains of the heavy or light chain of the antibody. As is known in the art, variable domains of the heavy chain and light chain (VH and VL, respectively) of an antibody generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three complementarity-determining regions (CDRs). (See, e.g., Kindt et al. Kuby Immunology, 6thed., W.H. Freeman and Co., page 91 (2007).) Many definitions for CDR sequences of an antibody variable domain are known in the art and may be used to describe an antibody of the present disclosure, e.g., by CDR sequences, including without limitation as defined by Kabat (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991), Chothia (see, e.g., Chothia and Lesk J. Mol. Biol. 196:901-917 (1987)), and IMGT (see, e.g., Lefranc, M.P. (1999) The Immunologist 7: 132-136). In some embodiments, CDR sequences of a single antibody are defined as by mixing two or more definitions, e.g., Kabat, Chothia, and / or IMGT.12MOFO-360690948Attorney Docket No. 18654-2001540

[0045] Framework (or “FR” as used herein) can refer to variable domain residues other than the CDR residues. The FR of a variable domain generally consists of four FR domains: FR1, FR2, FR3, and FR4. Accordingly, the CDR and FR sequences generally appear in the following sequence in VH (or VL): FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. In some embodiments, a FR1, FR2, FR3, and / or FR4 of the present disclosure refers to a human framework region, z.e., of the VH or VL domain.

[0046] The term “full-length antibody” as used herein refers to an antibody in its substantially intact form, as opposed to an antibody fragment. Specifically, full-length antibodies include those with heavy chains including an Fc region and light chains including a light chain constant domain. The Fc fragment comprises the carboxy-terminal portions of both H chains held together by disulfides. The effector functions of antibodies are determined by sequences in the Fc region, the region which is also recognized by Fc receptors (FcR) found on certain types of cells. The constant domains may be native sequence constant domains (e.g., human native sequence constant domains) or amino acid sequence variants thereof. In some cases, the intact antibody may have one or more effector functions. The C-terminal lysine (residue 447 according to the EU numbering system) of the Fc region may be removed, for example, during production or purification of the antibody, or by recombinantly engineering the nucleic acid encoding a heavy chain of the antibody.

[0047] A “human antibody” as used herein refers to an antibody that possesses an amino-acid sequence corresponding to that of an antibody produced by a human and / or has been made using any of the techniques for making human antibodies as disclosed herein. This definition of a human antibody specifically excludes a humanized antibody comprising non-human antigen-binding residues. Human antibodies can be produced using various techniques known in the art, including phage-display libraries as well as transgenic animals that have been modified to produce human antibodies in response to antigenic challenge, but whose endogenous loci have been disabled (see, e.g., U.S. Pat. Nos. 6,075,181 and 6,150,584).

[0048] The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, z.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations and / or post-translation modifications (e.g., isomerizations, amidations) that may be present in minor amounts. In contrast to polyclonal antibody preparations which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. The modifier "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies and is not to be construed as requiring production of the antibody by any particular method (e.g., hybridoma method, recombinant production, etc.).

[0049] As used herein, the terms “individual,” “patient,” or “subject” are used interchangeably and refer to any single animal, e.g., a mammal (including such non-human animals as, for example, dogs, cats, horses, rabbits, zoo animals, cows, pigs, sheep, and non-human primates) for which treatment is desired.13MOFO-360690948Attorney Docket No. 18654-2001540In particular embodiments, the patient herein is a human. In some embodiments, the human subject is an infant, a toddler, a child, a young adult, an adult or a geriatric.

[0050] The term “package insert” is used to refer to instructions customarily included in commercial packages of therapeutic products, that contain information about the indications, usage, dosage, administration, combination therapy, contraindications, and / or warnings concerning the use of such therapeutic products.

[0051] A “pharmaceutically acceptable carrier” refers to an ingredient in a pharmaceutical composition or formulation, other than an active ingredient, which is nontoxic to a subject. A pharmaceutically acceptable carrier includes, but is not limited to, a buffer, excipient, stabilizer, or preservative.

[0052] As used herein, “dibotatug” is a fully human, IgGl isotype, non-fucosylated antibody that comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:65 and a light chain comprising the amino acid sequence of SEQ ID NO:66. Dibotatug is also described in International Nonproprietary Names for Pharmaceutical Substances (INN) proposed INN List 130 (WHO Drug Information, Vol. 37, No. 4, 2023, p. 1015) and has CAS registry number 2842038-48-4. Dibotatug is also referred to as DR-01.IL Methods and Uses of Treatment

[0053] Certain aspects of the present disclosure relate to methods and uses for treating an autoimmune disease or disorder, e.g., in an individual in need thereof. In some embodiments, the methods comprise administering to the individual an anti-CD94 antibody of the present disclosure, e.g., at one or more doses of a dose selected from 24mg, 80mg, 240mg, or 450mg. In some embodiments, the autoimmune disease or disorder is alopecia areata (AA), vitiligo (VT), or lichen planus (LP). Anti-CD94 antibodies suitable for use in the methods and uses of the present disclosure are described in more detail in Section II infra. For example, in some embodiments, the anti-CD94 antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3, and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6. In some embodiments, the anti-CD94 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:65 and a light chain comprising the amino acid sequence of SEQ ID NO:66. In some embodiments, the anti-CD94 antibody is dibotatug.

[0054] In some embodiments, administration of the antibody results in a reduction in one or more symptoms of the autoimmune disease or disorder in the individual. In some embodiments, the terms treat, treating, treatment, ameliorate, ameliorating, reducing one or more symptoms, reducing symptoms, reduce one or more symptoms, reduce symptoms, and other grammatical equivalents, refer to alleviating, abating or ameliorating one or more symptoms of a disease or disorder, preventing additional symptoms, 14MOFO-360690948Attorney Docket No. 18654-2001540 ameliorating or preventing the underlying causes of symptoms, inhibiting the disease or disorder, e.g., arresting the development of the disease or disorder, relieving the disease or disorder, causing regression of the disease or disorder, relieving a condition caused by the disease or disorder, or stopping the symptoms of the disease or disorder, and are intended to include prophylaxis. In some embodiments, the terms further include achieving a therapeutic benefit and / or a prophylactic benefit. In some embodiments, a therapeutic benefit refers to eradication or amelioration of the underlying disease or disorder being treated. Also, a therapeutic benefit is achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disease or disorder such that an improvement is observed in the patient, notwithstanding that, in some embodiments, the patient is still afflicted with the underlying disease or disorder. For prophylactic benefit, the pharmaceutical compositions are administered to a patient at risk of developing a particular disease or disorder, or to a patient reporting one or more of the physiological symptoms of a disease or disorder, even if a diagnosis of the disease or disorder has not been made.

[0055] In some embodiments, administration of the antibody results in a reduction in the number of NK cells and / or T cells that express CD94 (z.e., CD94+ NK cells and / or T cells). In some embodiments, administration of the antibody results in a reduction in the number of peripheral blood NK cells and / or CD8+, gamma-delta, or CD8+ / CD4+ T cells in the subject, e.g., that express CD94. In some embodiments, administration of the antibody results in a reduction in the number of peripheral blood NK cells, e.g., that express CD94, in the subject. In some embodiments, administration of the antibody results in a reduction in the number of peripheral blood CD8+ / CD4+ T cells, e.g., that express CD94, in the subject. In some embodiments, administration of the antibody results in a reduction in the number of peripheral blood CD8+ T cells, e.g., that express CD94, in the subject. In some embodiments, administration of the antibody results in a reduction in the number of peripheral blood gamma-delta T cells, e.g., that express CD94, in the subject. In some embodiments, the reduction or depletion is by antibody-dependent cell-mediated cytotoxicity (ADCC) or antibody-dependent cell-mediated phagocytosis (ADCP). In some embodiments, administration of the antibody results in a reduction in the number of NK cells and / or CD8+, gamma-delta, or CD8+ / CD4+ T cells in the subject, e.g., that express CD94, in a sample obtained from the subject, e.g. , from a blood, blister fluid, or tissue (e.g. , skin lesion or skin biopsy) sample.

[0056] In some embodiments, the reduction in the number of peripheral blood NK cells and / or T cells that express CD94 in the subject occurs within the first 24 hours, e.g., any of within about 1 hour, within about 2 hours, within about 3 hours, within about 4 hours, within about 5 hours, within about 6 hours, within about 7 hours, within about 8 hours, within about 9 hours, within about 10 hours, within about 11 hours, within about 12 hours, within about 13 hours, within about 14 hours, within about 15 hours, within about 16 hours, within about 17 hours, within about 18 hours, within about 19 hours, within about 20 hours, within about 21 hours, within about 22 hours, within about 23 hours, or within about 24 hours after administration of the antibody to the subject.15MOFO-360690948Attorney Docket No. 18654-2001540

[0057] In some embodiments, the peripheral blood NK cells that express CD94 are CD3- CD56+. In some embodiments, the peripheral blood T cells that express CD94 are Vdelta T1 / 2+CD8+, or CD8+ and CD4+.

[0058] In some embodiments, the reduction in the number of peripheral blood NK cells and / or T cells that express CD94 in the subject is reversible. In some embodiments, the reduction in the number of peripheral blood NK cells and / or T cells that express CD94 in the subject is reversible within any of about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, or more, after administration of the antibody to the subject.

[0059] In some embodiments, a statement that a cell or a population of cells is positive (+) for, or expresses a particular marker (e.g., CD3, CD4, CD8, CD16, CD94, NKG2A, etc.), refers to the detectable presence on or in the cell of the particular marker. In some embodiments, a statement that a cell or a population of cells is positive for, +, or expresses a surface marker (e.g., a cell surface protein) refers to the presence of cell surface expression of the particular marker, for example, as detected by flow cytometry, for example, by staining with an antibody that specifically binds to the marker and detecting said antibody, wherein the staining is detectable by flow cytometry at a level substantially above the staining detected carrying out the same procedure with an isotype-matched control and / or fluorescence minus one (FMO) gating control under otherwise identical conditions, and / or at a level substantially similar to that for cell known to be positive for the marker, and / or at a level substantially higher than that for a cell known to be negative for the marker.

[0060] In some embodiments, a statement that a cell or a population of cells is negative (-) for, or does not express a particular marker (e.g., CD3, CD4, CD8, CD16, CD94, NKG2A, etc.) refers to the absence of a detectable presence on or in the cell of the particular marker. In some embodiments, a statement that a cell or a population of cells is negative for, -, or does not express a surface marker (e.g., a cell surface protein) refers to the absence of cell surface expression of the particular marker, for example, as detected by flow cytometry, for example, by staining with an antibody that specifically binds to the marker and detecting said antibody, wherein the staining is detectable by flow cytometry at a level substantially similar or below the staining detected carrying out the same procedure with an isotype-matched control and / or fluorescence minus one (FMO) gating control under otherwise identical conditions, and / or at a level below that for cell known to be positive for the marker, and / or at a level substantially similar or below that for a cell known to be negative for the marker.A. Administration and Dosing Regimens

[0061] In some embodiments, administer, administering, administration, and the like, refer to methods that are used to enable delivery of therapeutic or pharmaceutical compositions to the desired site of biological action. In some embodiments, an antibody of the disclosure (and any additional therapeutic agent) for use in any of the methods provided herein may be administered to the subject (e.g., a human) by 16MOFO-360690948Attorney Docket No. 18654-2001540 any suitable means, including parenteral, intrapulmonary, intranasal, and intralesional administration. Parenteral infusions include intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration. Dosing of an antibody of the disclosure can be by any suitable route, e.g., by injections, such as intravenous or subcutaneous injections, depending in part on whether the administration is brief or chronic. In some embodiments, an antibody or composition of the disclosure is administered by intravenous infusion.

[0062] In some embodiments, an anti-CD94 antibody of the present disclosure is administered (e.g., intravenously or subcutaneously) to an individual (e.g., in need thereof) at one or more doses of 24mg, 80mg, 240mg or 450mg (optionally as part of a pharmaceutical composition or an article of manufacture of the present disclosure). In some embodiments, the methods comprise administering to the individual two or more doses of 24mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprise administering to the individual two or more doses of 24mg of the antibody at an interval of 4 weeks or 28 days. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 24mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by a 24mg dose once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20. In some embodiments, the methods comprise administering (e.g., intravenously or subcutaneously) to the individual two or more doses of 24mg of dibotatug at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprise administering to the individual two or more doses of 24mg of dibotatug at an interval of 4 weeks or 28 days. For example, in some embodiments, dibotatug is administered to the individual at a dose of 24mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by a 24mg dose of dibotatug administered once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0063] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 24mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 24mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3, and a VL domain comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NON, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 24mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 24mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20. In some embodiments, the antibody comprises an Fc region (e.g. , a human IgGl Fc region, optionally a non-fucosylated human IgGl Fc region). In some embodiments, the antibody is an anti-CD94 antibody of the present disclosure that comprises a full-length, non-fucosylated human IgGl antibody. In some embodiments, the antibody is dibotatug.17MOFO-360690948Attorney Docket No. 18654-2001540

[0064] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 24mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 24mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain that comprises the amino acid sequence of SEQ ID NO: 16, and a VL domain that comprises the amino acid sequence of SEQ ID NO: 17. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 24mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 24mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20. In some embodiments, the antibody comprises an Fc region (e.g., a human IgGl Fc region, optionally a non-fucosylated human IgGl Fc region). In some embodiments, the antibody is an anti-CD94 antibody of the present disclosure that comprises a full-length, non-fucosylated human IgGl antibody.

[0065] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 24mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 24mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:65 and a light chain comprising the amino acid sequence of SEQ ID NO:66. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 24 mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 24mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0066] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 24mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 24mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain comprising three CDR sequences of a single VH domain shown in Table 1 and a VL domain comprising three CDR sequences of a single VL domain shown in Table 1. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 24mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 24mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0067] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 24mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 24mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain comprising a VH domain sequence shown in Table 2 and a VL domain comprising a VL domain sequence shown in Table 2. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of18MOFO-360690948Attorney Docket No. 18654-200154024mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 24mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0068] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 80mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprise administering to the individual two or more doses of 80mg of the antibody at an interval of 4 weeks or 28 days. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 80mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 80mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20. In some embodiments, the methods comprise administering (e.g., intravenously or subcutaneously) to the individual two or more doses of 80mg of dibotatug at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprise administering to the individual two or more doses of 80mg of dibotatug at an interval of 4 weeks or 28 days. For example, in some embodiments, dibotatug is administered to the individual at a dose of 80mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by an 80mg dose of dibotatug administered once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0069] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof)comprise administering to the individual two or more doses of 80mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 80mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3, and a VL domain comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NON, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 80mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 80mg doses once every 4 weeks, e.g, at Weeks 8, 12, 16, and 20. In some embodiments, the antibody comprises an Fc region (e.g. , a human IgGl Fc region, optionally a non-fucosylated human IgGl Fc region). In some embodiments, the antibody is an anti-CD94 antibody of the present disclosure that comprises a full-length, non-fucosylated human IgGl antibody. In some embodiments, the antibody is dibotatug.

[0070] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 80mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 80mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain that comprises the amino acid sequence of SEQ ID NO: 16, and a VL domain that comprises the amino acid sequence of SEQ ID NO: 17.19MOFO-360690948Attorney Docket No. 18654-2001540For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 80mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 80mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20. In some embodiments, the antibody comprises an Fc region (e.g., a human IgGl Fc region, optionally a non-fucosylated human IgGl Fc region). In some embodiments, the antibody is an anti-CD94 antibody of the present disclosure that comprises a full-length, non-fucosylated human IgGl antibody.

[0071] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 80mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 80mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:65 and a light chain comprising the amino acid sequence of SEQ ID NO:66. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 80mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 80mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0072] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 80mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 80mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain comprising three CDR sequences of a single VH domain shown in Table 1 and a VL domain comprising three CDR sequences of a single VL domain shown in Table 1. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 80mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 80mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0073] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 80mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 80mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain comprising a VH domain sequence shown in Table 2 and a VL domain comprising a VL domain sequence shown in Table 2. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 80mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 80mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0074] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 240mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further20MOFO-360690948Attorney Docket No. 18654-2001540 comprise administering to the individual two or more doses of 240mg of the antibody at an interval of 4 weeks or 28 days. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 240mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 240mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20. In some embodiments, the methods comprise administering (e.g., intravenously or subcutaneously) to the individual two or more doses of 240mg of dibotatug at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprise administering to the individual two or more doses of 240mg of dibotatug at an interval of 4 weeks or 28 days. For example, in some embodiments, dibotatug is administered to the individual at a dose of 240mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by a 240mg dose of dibotatug administered once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0075] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 240mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 240mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3, and a VL domain comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NON, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 240mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 240mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20. In some embodiments, the antibody is a human antibody. In some embodiments, the antibody comprises an Fc region (e.g., a human IgGl Fc region, optionally a non-fucosylated human IgGl Fc region). In some embodiments, the antibody is an anti- CD94 antibody of the present disclosure that comprises a full-length, non-fucosylated human IgGl antibody. In some embodiments, the antibody is dibotatug.

[0076] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 240mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 240mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain that comprises the amino acid sequence of SEQ ID NO: 16, and a VL domain that comprises the amino acid sequence of SEQ ID NO: 17. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 240mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 240mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20. In some embodiments, the antibody comprises an Fc region (e.g., a human IgGl Fc region, optionally a non-fucosylated human IgGl Fc region). In some21MOFO-360690948Attorney Docket No. 18654-2001540 embodiments, the antibody is an anti-CD94 antibody of the present disclosure that comprises a full-length, non-fucosylated human IgGl antibody.

[0077] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 240mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 240mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:65 and a light chain comprising the amino acid sequence of SEQ ID NO:66. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 240mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 240mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0078] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 240mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 240mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain comprising three CDR sequences of a single VH domain shown in Table 1 and a VL domain comprising three CDR sequences of a single VL domain shown in Table 1. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 240mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 240mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0079] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 240mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 240mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain comprising a VH domain sequence shown in Table 2 and a VL domain comprising a VL domain sequence shown in Table 2. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 240mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 240mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0080] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 450mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprise administering to the individual two or more doses of 450mg of the antibody at an interval of 4 weeks or 28 days. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 450mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 450mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20. In some embodiments, the methods comprise administering (e.g., intravenously or subcutaneously) to the individual two or more doses of 22MOFO-360690948Attorney Docket No. 18654-2001540450mg of dibotatug at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprise administering to the individual two or more doses of 450mg of dibotatug at an interval of 4 weeks or 28 days. For example, in some embodiments, dibotatug is administered to the individual at a dose of 450mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by a 450mg dose of dibotatug administered once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0081] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 450mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 450mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3, and a VL domain comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NON, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 450mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 450mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20. In some embodiments, the antibody is a human antibody. In some embodiments, the antibody comprises an Fc region (e.g., a human IgGl Fc region, optionally a non-fucosylated human IgGl Fc region). In some embodiments, the antibody is an anti- CD94 antibody of the present disclosure that comprises a full-length, non-fucosylated human IgGl antibody. In some embodiments, the antibody is dibotatug.

[0082] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 450mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 450mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain that comprises the amino acid sequence of SEQ ID NO: 16, and a VL domain that comprises the amino acid sequence of SEQ ID NO: 17. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 450mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 450mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20. In some embodiments, the antibody comprises an Fc region (e.g., a human IgGl Fc region, optionally a non-fucosylated human IgGl Fc region). In some embodiments, the antibody is an anti-CD94 antibody of the present disclosure that comprises a full-length, non-fucosylated human IgGl antibody.

[0083] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 450mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further23MOFO-360690948Attorney Docket No. 18654-2001540 comprising administering to the individual two or more doses of 450mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:65 and a light chain comprising the amino acid sequence of SEQ ID NO:66. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 450mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 450mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0084] In some embodiments, the methods (e.g., to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 450mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 450mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain comprising three CDR sequences of a single VH domain shown in Table 1 and a VL domain comprising three CDR sequences of a single VL domain shown in Table 1. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 450mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 450mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0085] In some embodiments, the methods (e.g, to treat an autoimmune disease or disorder in an individual in need thereof) comprise administering to the individual two or more doses of 450mg of the anti-CD94 antibody at an interval of 1 week or 7 days and / or 2 weeks or 14 days, and optionally further comprising administering to the individual two or more doses of 450mg of the antibody at an interval of 4 weeks or 28 days, wherein the anti-CD94 antibody comprises a VH domain comprising a VH domain sequence shown in Table 2 and a VL domain comprising a VL domain sequence shown in Table 2. For example, in some embodiments, the anti-CD94 antibody is administered to the individual at a dose of 450mg on Day 1, Day 8, Day 15, and Week 4, optionally followed by one or more 450mg doses once every 4 weeks, e.g., at Weeks 8, 12, 16, and 20.

[0086] In some embodiments, one or more doses of the antibody is / are administered to the individual (e.g, intravenously or subcutaneously) over a single day (e.g., a single dose of the antibody is administered to the individual as a single infusion). In some embodiments, one or more doses of the antibody is / are administered to the individual (e.g, intravenously or subcutaneously) split over two consecutive days. In some embodiments, the first dose of the antibody is administered to the individual (e.g., intravenously or subcutaneously) split over two consecutive days, e.g., on Days 1 and 2, with a first portion of the dose administered on Day 1, and the remaining portion of the dose administered on Day 2. In some embodiments, the first dose of the antibody is administered to the individual (e.g., intravenously or subcutaneously) split over two consecutive days, e.g. , on Days 1 and 2, with lOmg of the dose administered on Day 1, and the remaining portion of the dose administered on Day 2. In some embodiments, the first dose of the antibody is administered to the individual (e.g. , intravenously) split over two consecutive days, e.g., on Days 1 and 2, with lOmg of the dose administered on Day 1, and24MOFO-360690948Attorney Docket No. 18654-200154014mg of the dose administered on Day 2. In some embodiments, the first dose of the antibody is administered to the individual (e.g. , intravenously) split over two consecutive days, e.g. , on Days 1 and 2, with lOmg of the dose administered on Day 1, and 70mg of the dose administered on Day 2. In some embodiments, the first dose of the antibody is administered to the individual (e.g., intravenously) split over two consecutive days, e.g., on Days 1 and 2, with lOmg of the dose administered on Day 1, and 230mg of the dose administered on Day 2. In some embodiments, the dose of the antibody is intravenously administered to the individual in a single infusion on Day 8, Day 15, Week 4, Week 8, Week 12, Week 16, and Week 20.

[0087] In some embodiments, an anti-CD94 antibody of the present disclosure is administered (e.g., intravenously) to an individual (e.g., in need thereof) at a dose of 24mg on Day 1, Day 8, Day 15, Week 4, Week 8, Week 12, Week 16, and Week 20. In some embodiments, an anti-CD94 antibody of the present disclosure is administered (e.g., intravenously) to an individual (e.g., in need thereof) at a dose of lOmg on Day 1, 14mg on Day 2, 24mg on Day 8, 24mg on Day 15, 24mg on Week 4, 24mg on Week 8, 24mg on Week 12, 24mg on Week 16, and 24mg on Week 20. In some embodiments, an anti-CD94 antibody of the present disclosure is administered (e.g., intravenously or subcutaneously) to an individual (e.g., in need thereof) at a dose of 80mg on Day 1, Day 8, Day 15, Week 4, Week 8, Week 12, Week 16, and Week 20. In some embodiments, an anti-CD94 antibody of the present disclosure is administered (e.g., intravenously or subcutaneously) to an individual (e.g., in need thereof) at a dose of lOmg on Day 1, 70mg on Day 2, 80mg on Day 8, 80mg on Day 15, 80mg on Week 4, 80mg on Week 8, 80mg on Week 12, 80mg on Week 16, and 80mg on Week 20. In some embodiments, an anti-CD94 antibody of the present disclosure is administered (e.g., intravenously or subcutaneously) to an individual (e.g., in need thereof) at a dose of 240mg on Day 1, Day 8, Day 15, Week 4, Week 8, Week 12, Week 16, and Week 20. In some embodiments, an anti-CD94 antibody of the present disclosure is administered (e.g., intravenously or subcutaneously) to an individual (e.g., in need thereof) at a dose of lOmg on Day 1, 230mg on Day 2, 240mg on Day 8, 240mg on Day 15, 240mg on Week 4, 240mg on Week 8, 240mg on Week 12, 240mg on Week 16, and 240mg on Week 20. In some embodiments, an anti-CD94 antibody of the present disclosure is administered (e.g., intravenously or subcutaneously) to an individual (e.g., in need thereof) at a dose of 450mg on Day 1, Day 8, Day 15, Week 4, Week 8, Week 12, Week 16, and Week 20. In some embodiments, an anti-CD94 antibody of the present disclosure is administered (e.g., intravenously or subcutaneously) to an individual (e.g., in need thereof) at a dose of lOmg on Day 1, 440mg on Day 2, 450mg on Day 8, 450mg on Day 15, 450mg on Week 4, 450mg on Week 8, 450mg on Week 12, 450mg on Week 16, and 450mg on Week 20. In some embodiments, the antibody is dibotatug.

[0088] In some embodiments, one or more doses of the antibody is / are administered intravenously to the individual over 2-4 hours, 2-3 hours, 2 hours, 3 hours, or 4 hours. In some embodiments, the first dose of the antibody is intravenously administered to the individual split over two consecutive days, e.g., on Days 1 and 2, with a first portion of the dose administered over 4 hours on Day 1, and the remaining portion of the dose administered over 4 hours on Day 2. In some embodiments, the first dose of the antibody is25MOFO-360690948Attorney Docket No. 18654-2001540 intravenously administered to the individual split over two consecutive days, e.g., on Days 1 and 2, with lOmg of the dose administered over 4 hours on Day 1, and the remaining portion of the dose administered over 4 hours on Day 2. In some embodiments, the first dose of the antibody is intravenously administered to the individual split over two consecutive days, e.g., on Days 1 and 2, with lOmg of the dose administered over 4 hours on Day 1, and 14mg of the dose administered over 4 hours on Day 2. In some embodiments, the first dose of the antibody is intravenously administered to the individual split over two consecutive days, e.g., on Days 1 and 2, with lOmg of the dose administered over 4 hours on Day 1, and 70mg of the dose administered over 4 hours on Day 2. In some embodiments, the first dose of the antibody is intravenously administered to the individual split over two consecutive days, e.g., on Days 1 and 2, with lOmg of the dose administered over 4 hours on Day 1, and 230mg of the dose administered over 4 hours on Day 2. In some embodiments, after the first dose, the antibody is intravenously administered to the individual over 2-3 hours. In some embodiments the second and third doses of the antibody are intravenously administered to the individual over 3 hours, e.g., on Day 8 and Day 15. In some embodiments one or more dose(s) of the antibody is / are intravenously administered to the individual over 2 hours, e.g., at Weeks 4, 8, 12, 16, and / or 20. In some embodiments, the antibody is dibotatug.

[0089] In some embodiments, one or more premedication(s) is / are administered to the individual prior to one or more doses of the antibody, e.g., to reduce the likelihood and / or severity of infusion-related reactions (IRRs). In some embodiments, the methods further comprise administering a corticosteroid to the individual prior to one or more doses of the antibody. In some embodiments, the corticosteroid is methylprednisolone or an equivalent thereof. In some embodiments, 80mg methylprednisolone is administered intravenously to the individual at least 60 minutes and no more than 3 hours prior to the one or more dose(s) of the antibody. In some embodiments, 80mg methylprednisolone is administered intravenously to the individual at least 60 minutes and no more than 3 hours prior to the first dose of the antibody, e.g., on Day 1 and optionally Day 2. In some embodiments, 80mg methylprednisolone is administered intravenously to the individual at least 60 minutes and no more than 3 hours prior to the first portion of the first dose on Day 1, and 80mg methylprednisolone is administered intravenously to the individual at least 60 minutes and no more than 3 hours prior to the remaining portion of the first dose on Day 2.

[0090] In some embodiments, the methods further comprise administering an anti-pyretic to the individual prior to one or more doses of the antibody. In some embodiments, the anti-pyretic is acetaminophen (paracetamol) or an equivalent thereof. In some embodiments, 650-1000mg acetaminophen is administered orally to the individual at least 30 minutes and no more than 3 hours prior to one or more doses of the antibody.

[0091] In some embodiments, the methods further comprise administering an antihistamine to the individual prior to one or more doses of the antibody. In some embodiments, the antihistamine is diphenhydramine, cetirizine, loratadine, chlorpheniramine, brompheniramine, promethazine, hydroxyzine, fexofenadine, desloratadine, or levocetirizine. In some embodiments, the antihistamine is26MOFO-360690948Attorney Docket No. 18654-2001540 diphenhydramine or an equivalent thereof. In some embodiments, 50mg diphenhydramine is administered orally to the individual at least 30 minutes and no more than 3 hours prior to one or more doses of the antibody. In some embodiments, the antihistamine is cetirizine or an equivalent thereof. In some embodiments, cetirizine is administered orally to the individual at least 30 minutes and no more than 3 hours prior to one or more doses of the antibody. In some embodiments, the antihistamine is loratadine or an equivalent thereof. In some embodiments, lOmg loratadine is administered orally to the individual at least 30 minutes and no more than 3 hours prior to one or more doses of the antibody.

[0092] In some embodiments, 80mg methylprednisolone is administered intravenously to the individual at least 60 minutes and no more than 3 hours prior to the first portion of the first dose on Day 1, 80mg methylprednisolone is administered intravenously to the individual at least 60 minutes and no more than 3 hours prior to the remaining portion of the first dose on Day 2, 50mg diphenhydramine is administered orally to the individual at least 30 minutes and no more than 3 hours prior to the first portion of the first dose on Day 1, 50mg diphenhydramine is administered orally to the individual at least 30 minutes and no more than 3 hours prior to the remaining portion of the first dose on Day 2, 650-1000mg acetaminophen is administered orally to the individual at least 30 minutes and no more than 3 hours prior to the first portion of the first dose on Day 1, and 650-1000mg acetaminophen is administered orally to the individual at least 30 minutes and no more than 3 hours prior to the remaining portion of the first dose on Day 2. In some embodiments, 650-1000mg acetaminophen is administered orally to the individual at least 30 minutes and no more than 3 hours prior to the anti-CD94 antibody at Day 8, Day 15, Week 4, Week 8, and Week 12, and 50mg diphenhydramine is administered orally to the individual at least 30 minutes and no more than 3 hours prior to the anti-CD94 antibody at Day 8, Day 15, Week 4, Week 8, and Week 12. In some embodiments, 650-1000mg acetaminophen is administered orally to the individual at least 30 minutes and no more than 3 hours prior to the anti-CD94 antibody at Weeks 4, 8, and 12, and 50mg diphenhydramine is administered orally to the individual at least 30 minutes and no more than 3 hours prior to the anti- CD94 antibody at Weeks 4, 8, and 12.

[0093] In any of the above embodiments, the autoimmune disease or disorder is selected from Felty’s syndrome, rheumatoid arthritis (RA), inclusion body myositis, alopecia areata (AA), lichen planus (e.g., cutaneous lichen planus, oral lichen planus, cutaneous lichen planus, esophageal lichen planus, lichen planopilaris (LPP), or another form of lichen planus disclosed herein or known in the art) or vitiligo (VT). For example, in some embodiments, the LP is cutaneous or oral LP.B. Autoimmune Diseases or Disorders

[0094] Certain aspects of the present disclosure relate to methods of treatment for an autoimmune disease or disorder, e.g., in an individual in need thereof. In some embodiments, the autoimmune disease or disorder is rheumatoid arthritis (RA), Felty’s syndrome, inclusion body myositis, alopecia areata (AA), vitiligo (VT), or lichen planus (e.g., cutaneous lichen planus, oral lichen planus, cutaneous lichen planus,27MOFO-360690948Attorney Docket No. 18654-2001540 esophageal lichen planus, lichen planopilaris (LPP), or another form of lichen planus disclosed herein or known in the art).

[0095] Rheumatoid arthritis is an autoimmune disorder that primarily affects the joints but can also affect other organs and can be associated with cardiovascular disease, osteoporosis, interstitial lung disease, infection, cancer, fatigue, and depression. Symptoms of rheumatoid arthritis include swollen, tender, and warm joints, joint inflammation joint pain,joint stiffness, splenomegaly, rheumatoid nodules (e.g., in the skin), necrotizing granuloma, vasculitis, pyoderma gangrenosum, Sweet’s syndrome, drug reactions, erythema nodsum, lobe pannicultis, atrophy of finger skin, palmar erythema, skin fragility, diffuse alopecia areata, lung fibrosis, Caplan’s syndrome, exudative pleural effusions, atherosclerosis, myocardial infarction, stroke, pericarditis, endocarditis, left ventricular failure, valvulitis, fibrosis of the heart and / or blood vessels, anemia, increased platelet count, low white blood cell count, renal amyloidosis, episcleritis, scleritis, keratoconjuctivitis sicca, keratitis, loss of vision, liver problems, peripheral neuropathy, mononeuritis multiplex, carpal tunnel syndrome, myelopathy, atlanto-axial subluxation, vertebrae slipping, fatigue, low grade fever, malaise, morning stiffness, loss of appetite, loss of weight, osteoporosis, cancer (e.g., lymphoma, skin cancer), and periodontitis. In some embodiments of the methods provided herein, the disease or disorder is rheumatoid arthritis, and administration of the antibody results in a reduction in one or more rheumatoid arthritis symptoms in the subject. In some embodiments, the individual to be treated using the methods of the present disclosure has or has been diagnosed with rheumatoid arthritis.

[0096] In some embodiments, symptoms and disease status / progression of rheumatoid arthritis are measured according to the 2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria (see, e.g., Aletaha et al., (2010) Annals of Rheumatic Diseases, 69(9): 1580-8). Symptoms of rheumatoid arthritis may also be measured by any method known in the art, such as using laboratory tests to measure erythrocyte sedimentation rates, C-reactive protein, rheumatoid factor, anti-citrullinated protein antibodies, anemia and other cytopenias, increased platelet count, low white blood cell count, complete blood counts, renal amyloidosis, medical imaging such as X-rays, MRI, CT-scans, ultrasound (e.g., ultrasonography using a high-frequency transducer; Doppler ultrasound), flow cytometry, disease activity score-28 (DAS-28), and DAS-28 with erythrocyte sedimentation rate (ESR).

[0097] Felty’s syndrome is an autoimmune disease characterized by rheumatoid arthritis, splenomegaly (e.g., inflammatory splenomegaly), and a reduced number of neutrophils in the blood. Symptoms of Felty’s syndrome include painful, stiff, and / or swollen joints, physical findings associated with rheumatoid arthritis, splenomegaly, neutropenia, infections, keratoconjunctivitis sicca, fever, weight loss, fatigue, discoloration of the skin, sores (e.g., ulcers), hepatomegaly, anemia, thrombocytopenia, abnormal liver function, enlarged lymph nodes, and vasculitis. In some embodiments of the methods provided herein, the disease or disorder is Felty’s syndrome, and administration of the antibody results in a reduction in one or more Felty’s syndrome symptoms in the subject. Symptoms of Felty’s syndrome include, without limitationjoint inflammation, joint pain, and splenomegaly. In some embodiments, the28MOFO-360690948Attorney Docket No. 18654-2001540 individual to be treated using the methods of the present disclosure has or has been diagnosed with Felty’s syndrome.

[0098] Symptoms of Felty’s syndrome may be measured by any method known in the art, such as using laboratory tests to measure anemia, neutropenia, thrombocytopenia, and other cytopenias, complete blood counts, magnetic resonance imaging (MRI), CT scan, or ultrasound (e.g., to determine splenomegaly and / or hepatomegaly), laboratory tests for abnormal liver function, palpation to determine splenomegaly and / or hepatomegaly, flow cytometry, disease activity score-28 (DAS-28, e.g., as used for monitoring rheumatoid arthritis symptoms), and DAS-28 with erythrocyte sedimentation rate (ESR).

[0099] Inclusion Body Myositis (IBM), also referred to as sporadic inclusion body myositis, is an inflammatory muscle disease characterized by autoimmune and degenerative processes that result in progressive weakness and wasting of distal and / or proximal muscles. Generally, IBM is characterized by invasion of immune cells into muscle tissues. In some cases, patients with IBM have elevated creatine kinase levels in the blood. Symptoms of IBM include progressive muscle weakness, muscle wasting / atrophy, frequent tripping and falling, difficulty manipulating fingers, foot drop, restricted mobility, impaired balance, muscle pain, dysphagia, and fatigue. In some embodiments of the methods provided herein, the disease or disorder is IBM, and administration of the antibody results in a reduction in one or more IBM symptoms in the subject. In some embodiments, the individual to be treated using the methods of the present disclosure has or has been diagnosed with IBM.

[0100] Symptoms of IBM may be measured by any method known in the art, such as muscle biopsies, blood tests (e.g., to measure creatine kinase), electromyography (EMG) studies, blood tests to measure antibodies to NT5C1A, flow cytometry, and myositis disease activity assessment tools including without limitation Myositis Intention to Treat Activity Index (MITAX) and Myositis Disease Activity Assessment Visual Analogue Scales (MYOACT).

[0101] Alopecia areata (AA) is an autoimmune disease characterized by non-scarring hair loss of the scalp and other hair-bearing areas of the body. AA symptoms include patchy hair loss and red, brittle, and pitted finger and toe nails. In some embodiments of the methods provided herein, the disease or disorder is AA, and administration of the antibody results in a reduction in one or more AA symptoms in the subject. In some embodiments, AA symptoms are measured by Severity of Alopecia Tool (SALT) score. SALT divides the scalp into quadrants that are scored for hair loss, then combined into a sum score (Olsen, E. et al. (1999) J Am Acad Dermatol. 40(2 Pt 1) :242-246) . In some embodiments, the methods of the present disclosure result in at least a 30%, at least a 50%, at least a 75%, at least a 90%, or a 100% improvement in SALT score, e.g., as compared to a baseline SALT score obtained prior to treatment.

[0102] In some embodiments, the individual to be treated using the methods of the present disclosure has or has been diagnosed with alopecia areata. In some embodiments, the AA is moderate to severe AA. In some embodiments, the AA is moderate AA. In some embodiments, the AA is severe AA. In some embodiments, prior to administration of the antibody, the individual has a current episode of AA lasting from greater than 6 months to less than 10 years. In some embodiments, the individual does not have29MOFO-360690948Attorney Docket No. 18654-2001540 diffuse AA. In some embodiments, the AA is not diffuse AA. In some embodiments, prior to treatment according to the methods of the present disclosure, the individual has or has been diagnosed with moderate to severe AA with greater than 20% scalp hair loss, e.g., as defined by SALT. In some embodiments, prior to treatment according to the methods of the present disclosure, the individual has a current episode of AA, e.g. , lasting from greater than 6 months to less than 10 years. In some embodiments, prior to treatment according to the methods of the present disclosure, the individual has a current AA episode lasting greater than or equal to 10 years but has experienced hair regrowth in affected areas of the scalp, e.g., in the last 10 years. In some embodiments, prior to treatment according to the methods of the present disclosure, the individual has experienced no spontaneous improvement in AA symptoms in the 6 months prior to treatment. In some embodiments, the AA is not diffuse AA or another form of alopecia or active inflammatory disease of the scalp. In some embodiments, prior to treatment according to the methods of the present disclosure, the individual has not been treated with phototherapy, platelet-rich plasma injections, or non-steroid topical immunosuppressives within 12 weeks or 5 half-lives prior to treatment. In some embodiments, the individual is not treated with phototherapy, platelet-rich plasma injections, or non-steroid topical immunosuppressives during treatment according to the methods of the present disclosure. In some embodiments, prior to treatment according to the methods of the present disclosure, the individual does not have history of disseminated / complicated herpes zoster, or history of eczema herpeticum within 12 months prior to treatment or 2 or more prior episodes of eczema herpeticum.

[0103] Vitiligo (VT) is a depigmenting skin disorder resulting from autoimmune loss of melanocytes leading to loss of pigment in the affected areas of the skin (Bergqvist, C. et al. (2020) Dermatology 236(6): 571-592). In some embodiments, VT symptoms are measured by change (e.g., mean change) from baseline according to Vitiligo Area Scoring Index (VASI). VASI quantifies the severity of VT over the entire body (e.g., T-VASI) and includes the sub-component facial VASI (F-VASI) that scores VT severity in the face (Hamzavi, I. et al. (2004) Arch Dermatol. 140(6): 677-683) . In some embodiments, the methods of the present disclosure result in at least a 50% or at least a 75% improvement in VASI score, e.g. , as compared to a baseline VASI score obtained prior to treatment. In some embodiments, the methods of the present disclosure result in at least a 50% or at least a 75% improvement in T-VASI score, e.g. , as compared to a baseline T-VASI score obtained prior to treatment. In some embodiments, the methods of the present disclosure result in at least a 50% or at least a 75% improvement in F-VASI score, e.g., as compared to a baseline F-VASI score obtained prior to treatment.

[0104] In some embodiments, the individual to be treated using the methods of the present disclosure has or has been diagnosed with vitiligo. In some embodiments, the VT is active VT. In some embodiments, the VT is stable VT. In some embodiments, the VT is non-segmental VT. In some embodiments, the VT is mixed VT. In some embodiments, the VT is active or stable non-segmental VT. In some embodiments, the individual to be treated using the methods of the present disclosure has or has been diagnosed with non-segmental VT for at least 3 months. In some embodiments, prior to treatment 30MOFO-360690948Attorney Docket No. 18654-2001540 according to the methods of the present disclosure, the individual has VT body surface area (BSA) involvement of between 4% and 60% (inclusive), excluding involvements at palms of the hands, dorsal aspect of fingers and thumbs including metacarpophalangeal joints, soles of the feet, or dorsal aspect of the feet. In some embodiments, prior to treatment according to the methods of the present disclosure, the individual has BSA involvement of greater than or equal to 0.25% on the face, excluding involvement at vermilion. In some embodiments, prior to treatment according to the methods of the present disclosure, the individual has at least 1 active lesion. In some embodiments, an active lesion is defined as one or more of: new / extending lesion(s) in the past 3 months, confetti-like lesion(s), trichome lesion(s), and Koebner phenomenon / phenomena (excluding Type 1 [history based isomorphic reaction]). In some embodiments, prior to treatment according to the methods of the present disclosure, the individual has coexistence of halo nevus / nevi (also known as Sutton nevus / nevi). In some embodiments, prior to treatment according to the methods of the present disclosure, the individual does not have an active form of another hypopigmentation disease or disorder, including but not limited to Vogt-Koyanagi-Harada disease, malignancy-induced hypopigmentation [melanoma and mycosis fimgoides], post-inflammatory hypopigmentation, pityriasis alba [minor manifestation of atopic dermatitis], senile leukoderma [age- related depigmentation], chemical / drug -induced leukoderma, ataxia telangiectasia, tuberous sclerosis, melasma, and congenital hypopigmentation disorders including piebaldism, Waardenburg syndrome, hypomelanosis of Ito, incontinentia pigmenti, dyschromatosis symmetrica hereditaria, xeroderma pigmentosum, and nevus depigmentosus. In some embodiments, prior to treatment according to the methods of the present disclosure, the individual does not have an active form of another inflammatory skin disease / disorder or skin condition, including but not limited to morphea, discoid lupus, leprosy, syphilis, psoriasis, seborrheic dermatitis. In some embodiments, prior to treatment according to the methods of the present disclosure, the individual does not have a history of eczema herpeticum within 12 months prior to screening or a history of 2 or more episodes of eczema herpeticum in the past. In some embodiments, the individual is not treated with permanent depigmentation treatment (e.g. , monobenzene or phenol) during treatment according to the methods of the present disclosure. In some embodiments, prior to treatment according to the methods of the present disclosure, the individual has not been treated with ultraviolet B phototherapy, psoralen ultraviolet A therapy, or other phototherapy within 4 weeks of treatment. In some embodiments, prior to treatment according to the methods of the present disclosure, the individual does not have history of disseminated / complicated or relapsing herpes zoster, or history of eczema herpeticum within 12 months prior to treatment or 2 or more prior episodes of eczema herpeticum.

[0105] In some embodiments, prior to treatment according to the methods of the present disclosure, the individual does not have any of the following:• Participation in an investigational drug or device trial in which administration of an investigational drug or device occurred within 28 days or 5 half-lives of screening, whichever is shorter31MOFO-360690948Attorney Docket No. 18654-2001540• Use of live vaccines during the study and within 28 days prior to screening• Known history of chronic alcohol abuse, IV drug abuse, or illicit drug abuse within 1 year before screening• Diagnosis or history of malignant disease within 5 years prior to baseline, with the exceptions of basal cell or squamous epithelial carcinomas of the skin that have been resected or cervical carcinoma in situ, with no evidence of recurrence within the 5 years prior to baseline• Any surgical procedure (except for minor surgery requiring local or no anesthesia and without any complications or sequelae) within 12 weeks prior to screening, or any planned surgical procedure scheduled to occur during the study• Any of the following types of infection within 28 days of screening or before randomization: o Serious (requiring hospitalization and / or IV anti-infective treatment) o Chronic (duration of symptoms, signs, and / or treatment of 6 weeks or longer) o Viral reactivation of cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella-zoster virus (VZV) or herpes simplex virus type (HSV) infection requiring systemic therapy in the last 2 years• Any of the following: o Human immunodeficiency virus (HIV) infection o Current infection with hepatitis B virus (HBV) (i.e., positive for hepatitis B surface antigen and / or polymerase chain reaction positive for HBV DNA) o Current infection with hepatitis C virus (HCV) (i.e., positive for HCV RNA)• Concurrent diagnosis or history of any autoimmune diseases other than AA or VT requiring systemic or topical immunotherapy• Use of topical and oral JAK inhibitors within 4 and 8 weeks of randomization, respectively• Use of lymphocyte depleting agents (e.g., rituximab, ocrelizumab, ofatumumab, ublituximab, thymoglobulin, alemtuzumab, etc.) within 6 months of screening or until lymphocyte counts have normalized• Use of other biologies within 4 weeks of screening• Use of oral immune suppressants (e.g., cyclosporine A, azathioprine, methotrexate, sulfasalazine, systemic corticosteroids, my cophenolate -mofetil) within 28 days of screening. Topical steroid use is prohibited within 2 weeks of screening in VT and on scalp, eyebrows, and eyelids in AA• Intralesional steroid injection within 8 weeks of screening or within 5 half-lives, whichever is longer• Herbal medications, including traditional Chinese medicine formulations, with unknown properties or known beneficial effects for VT or alopecia32MOFO-360690948Attorney Docket No. 18654-2001540• Untreated latent tuberculosis as indicated by IFNy release assay, without documentation of appropriate treatment (appropriate therapy as defined by the World Health Organization and / or the United States Centers for Disease Control and Prevention)• Estimated glomerular filtration rate < 30 mE / min / 1 ,73m2(using the Chronic Kidney Disease Epidemiology Collaboration formula; Levey, A.S. et al. (2009) Ann Intern Med. 150(9):604-612)• Total bilirubin >1.5 upper limit of normal (ULN; >3 x ULN if known Gilbert’s disease)• Aspartate aminotransferase and alanine aminotransferase > 2.5 x ULN

[0106] Lichen planus (LP) is a chronic, inflammatory disease that can involve the skin, oral mucosa, genitals, nails, esophagus, and other areas. Symptoms of LP may be measured by any method known in the art. In some embodiments, LP symptoms are measured by Physician Global Assessment (PGA) of skin with treatment response defined as PGA 0 to 3. In some embodiments, the methods of the present disclosure results in at least a 50% PGA score reduction, e.g., as compared to PGA score prior to treatment. In some embodiments, LP symptoms are measured by changes in modified Composite Assessment of Index Lesion Severity (mCAILS). In some embodiments, LP symptoms are measured by total body lesion count. In some embodiments, LP symptoms are measured by affected BSA. In some embodiments, LP symptoms are measured by pruritus numeric rating scale (NRS). In some embodiments, LP symptoms are measured by pruritus verbal rating scale (VRS). In some embodiments, LP symptoms are measured by pruritus visual analog scale (VAS). In some embodiments, LP symptoms are measured by pain NRS. In some embodiments, LP symptoms are measured by and Skindex-16.

[0107] In some embodiments, the individual to be treated using the methods of the present disclosure has or has been diagnosed with LP. In some embodiments, the LP is cutaneous LP or oral LP. In some embodiments, the LP is mucosal LP. In some embodiments, the LP is appendageal LP. In some embodiments, the LP is lichen planopilaris (LPP).III. Antibodies

[0108] A variety of anti-CD94 antibodies suitable for use in the methods of the present disclosure are provided infra. In some embodiments, the anti-CD94 antibodies bind to CD94 and have immunoglobulin Pc part with modifications including reduced fucosylation, non-fucosylation, or mutations that enhance ADCC activities and / or improve affinity of the Fc region to Fc receptors such as CD16 (e.g., CD16a). In some embodiments, the anti-CD94 antibodies have one or more of the following characteristics: bind to human CD94 and cynomolgus monkey CD94, do not block binding of HLA-E to the CD94 / NKG2A heterodimer, have a low degree of target (e.g., CD94) internalization, are non-fucosylated or have reduced fucosylation, and / or induce or promote ADCC activity.A. Antibody Targets and Affinities

[0109] In some embodiments, the antibodies provided herein bind to CD94. In some embodiments, the antibodies provided herein bind to human CD94 (e.g., an extracellular domain of human CD94). In some33MOFO-360690948Attorney Docket No. 18654-2001540 embodiments, the antibodies provided herein bind to cynomolgus monkey CD94 (e.g., an extracellular domain of cynomolgus CD94). In some embodiments, the antibodies provided herein bind to human CD94 and to cynomolgus monkey CD94. In some embodiments, an antibody of the disclosure binds to CD94 on the surface ofNK cells and / or T cells.

[0110] In some embodiments, an antibody of the disclosure binds to a human CD94 protein or a part thereof, or a protein having at least 80% (e.g., any of at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) homology to a human CD94 protein or a part thereof. Amino acid sequences of exemplary human CD94 proteins are provided in the sequences of SEQ ID NOs: 42-44:MAVFKTTLWRLISGTLGIICLSLMSTLGILLKNSFTKLSIEPAFTPGPNIELQKDSDCCSCQEKWVGYRCNCYFISSEQKTWNESRHLCASQKSSLLQLQNTDELDFMSSSQQFYWIGLS YSEEHTAWLWENGSALSQYLFPSFETFNTKNCIAYNPNGNALDESCEDKNRYICKQQLI ( SEQ ID NO :42 )MAVFKTTLWRLISGTLGIICLSLMSTLGILLKNSFTKLSIEPAFTPGPNIELQKDSDCCS CQEKWVGYRCNCYFISSEQKTWNESRHLCASQKSSLLQLQNTDELQDFMSSSQQFYWIGLSYSEEHTAWLWENGSALSQYLFPSFETFNTKNCIAYNPNGNALDESCEDKNRYICKQQLI ( SEQ ID NO : 43 )MAAFTKLSIEPAFTPGPNIELQKDSDCCSCQEKWVGYRCNCYFISSEQKTWNESRHLCAS QKSSLLQLQNTDELDFMSSSQQFYWIGLSYSEEHTAWLWENGSALSQYLFPSFETFNTKN CIAYNPNGNALDESCEDKNRYICKQQLI SYSEEHTAWLWENGSALSQYLFPSFETFNTKNCIAYNPNGNALDESCEDKNRYICKQQLI ( SEQ ID NO : 44 )[oni] In some embodiments, the terms bind, specifically binds to, or is specific for refer to measurable and reproducible interactions such as binding between a target and an antibody, which is determinative of the presence of the target in the presence of a heterogeneous population of molecules including biological molecules. For example, an antibody that binds to or specifically binds to a target (which can be an epitope) is an antibody that binds this target with greater affinity, avidity, more readily, and / or with greater duration than it binds to other targets. In one embodiment, the extent of binding of an antibody to an unrelated target is less than about 10% of the binding of the antibody to the target as measured, e.g., by a radioimmunoassay (RIA). In certain embodiments, an antibody that specifically binds to a target has a dissociation constant (KD) of < IpM, < 100 nM, < 10 nM, < 1 nM, or < 0.1 nM. In certain embodiments, an antibody specifically binds to an epitope on a protein that is conserved among the protein from different species. In another embodiment, specific binding can include, but does not require exclusive binding.34MOFO-360690948Attorney Docket No. 18654-2001540

[0112] In some embodiments, the antibodies provided herein bind to human CD94 (Natural killer cells antigen CD94; CD94 Entrez Gene ID: 3824; KLRD1 (HGNC Symbol); UniProtKB identifier: Q13241; HGNC6378; Ensembl: ENSG00000134539 OMIM: 602894; KP43).

[0113] In some embodiments, an antibody of the disclosure binds to a cynomolgus monkey CD94 protein or a part thereof, or a protein having at least 80% (e.g., any of at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) homology to a cynomolgus monkey CD94 protein or a part thereof. The amino acid sequences of cynomolgus monkey CD94 proteins are known in the art, for example, UniProtKB identifier: Q68VD4.

[0114] In certain embodiments, the affinity of an antibody for its target (e.g., CD94) may be represented by the dissociation constant (KD). Affinity can be measured by common methods known in the art, such as flow cytometry or Western blotting, and using assays described herein (e.g., in the Examples). In some embodiments, the KDis measured using a radiolabeled antigen binding assay (RIA) performed with the Fab version of an antibody of the disclosure and its target (e.g., CD94). In some embodiments, the KD is measured using surface plasmon resonance assays. Exemplary assays are described, e.g., in Drake, A.W. and Klakamp, S.L. (2007) Immunol. Methods 318: 147-152.

[0115] In some embodiments, the binding of an antibody of the disclosure to CD94, e.g., human CD94 and / or cynomolgus monkey CD94, may be assessed using any method known in the art. For example, binding of an antibody of the disclosure to human CD94 may be assessed in an ex vivo flow cytometrybased assay using peripheral blood mononuclear cells (PMBCs) and / or NK cells, e.g., as described in the Examples. Titration curves and EC50 may be generated and evaluated using methods known in the art, such as using Graphpad prism. In another example, binding of an antibody of the disclosure to cynomolgus monkey CD94 may be assessed in an ex vivo or in vitro flow cytometry-based assay using cynomolgus monkey CD94-expressing cells such as cynomolgus monkey CD94-expressing HEK293 cells, e.g., as described in the Examples.

[0116] In certain embodiments, an antibody of the disclosure has a KDof less than about 10 pM for binding to its target (e.g., human and / or cynomolgus CD94). In certain embodiments, an antibody of the disclosure has a KDof less than about 1 pM for binding to its target (e.g., human and / or cynomolgus CD94). In certain embodiments, an antibody of the disclosure has a KDof any of less than about 1000 nM, less than about 900 nM, less than about 800 nM, less than about 700 nM, less than about 600 nM, less than about 500 nM, less than about 400 nM, less than about 300 nM, less than about 200 nM, less than about 100 nM, less than about 90 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 9 nM, less than about 8 nM, less than about 7 nM, less than about 6 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM, less than about 0.5 nM, or less than about 0.1 nM for binding to its target (e.g., human and / or cynomolgus CD94). In some embodiments, an antibody of the disclosure has a KD of any of less than about 100 pM, less than about 75 pM, less than about 50 pM, less than about 25 pM, less than about 1035MOFO-360690948Attorney Docket No. 18654-2001540 pM, less than about 5 pM, less than about 1 pM, less than about 0.5 pM, or less than about 0.1 pM for binding to its target (e.g., human and / or cynomolgus CD94).

[0117] In certain embodiments, an antibody of the disclosure has a KD of less than about 100 nM, less than about 90 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 9 nM, less than about 8 nM, less than about 7 nM, less than about 6 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM, less than about 0.5 nM, or less than about 0.1 nM for binding to human CD94 on human NK cells or T cells. In certain embodiments, an antibody of the disclosure has a KDof less than about 75 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 9 nM, less than about 8 nM, less than about 7 nM, less than about 6 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM, less than about 0.5 nM, or less than about 0.1 nM for binding to human CD94 on human NK cells or T cells. In certain embodiments, an antibody of the disclosure has a KD of between about 2 nM and about 80 nM for binding to human CD94 on human NK cells or T cells.

[0118] In certain embodiments, an antibody of the disclosure has a KD of less than about 100 nM, less than about 90 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 9 nM, less than about 8 nM, less than about 7 nM, less than about 6 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM, less than about 0.5 nM, or less than about 0.1 nM for binding to cynomolgus CD94 on cells expressing cynomolgus monkey CD94. In certain embodiments, an antibody of the disclosure has a KDof less than about 75 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 9 nM, less than about 8 nM, less than about 7 nM, less than about 6 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM, less than about 0.5 nM, or less than about 0. 1 nM for binding to cynomolgus CD94 on cells expressing cynomolgus monkey CD94. In certain embodiments, an antibody of the disclosure has a KDof between about 2 nM and about 80 nM for binding to cynomolgus CD94 on cells expressing cynomolgus monkey CD94.

[0119] In some embodiments, an antibody of the disclosure binds to its target (e.g., CD94) in the same or a different epitope as an antibody known in the art for that target. In some embodiments, an antibody of the disclosure binds to a different epitope as an antibody known in the art. In some embodiments, an antibody of the disclosure specifically binds to human CD94, wherein the antibody does not bind to the same epitope on human CD94 as anti-CD94 antibody clones HP-3D9, DX22, HP-3B1, 131412, or 12K45. In some embodiments, an antibody of the disclosure specifically binds to human CD94, wherein the antibody does not bind to the same epitope on human CD94 as anti-CD94 antibody clones DX22,36MOFO-360690948Attorney Docket No. 18654-2001540HP-3B1, or 131412. In some embodiments, an antibody of the disclosure specifically binds to human CD94, wherein the antibody binds to the same epitope on human CD94 as anti-CD94 antibody clones HP-3D9, DX22, HP-3B1, 131412, or 12K45. In some embodiments, an antibody of the disclosure specifically binds to human CD94, wherein the antibody binds to the same epitope on human CD94 as anti-CD94 antibody clone HP-3D9. In some embodiments, an antibody of the disclosure specifically binds to human CD94, wherein the antibody binds to the same epitope on human CD94 as anti-CD94 antibody clone 12K45.

[0120] In some embodiments, if an antibody of the disclosure does not bind to its target (e.g., CD94,) in the same epitope as another antibody for that target, e.g., a commercially available antibody or an antibody known in the art for that target, then the antibody of the disclosure does not block binding of the other antibody to the target in a competition assay (e.g., as described in the Examples), e.g., by 50% or more.

[0121] In some embodiments, an antibody of the disclosure binds to its target (e.g., CD94) with a higher affinity than an antibody known in the art for that target. In some embodiments, an antibody of the disclosure binds to its target (e.g., CD94) with a higher affinity than anti-CD94 antibody clones HP-3D9, DX22, HP-3B1, 131412, or 12K45. In some embodiments, an antibody of the disclosure binds to its target (e.g., CD94) with a higher affinity than anti-CD94 antibody clones HP-3B1, 131412, or 12K45.

[0122] In some embodiments, an antibody of the disclosure specifically binds to human CD94, wherein the antibody binds to human CD94 with a greater affinity than anti-CD94 antibody clones HP-3D9, DX22, HP-3B1, 131412, or 12K45. In some embodiments, an antibody of the disclosure specifically binds to human CD94, wherein the antibody binds to human CD94 with a greater affinity than anti-CD94 antibody clones HP-3B1, 131412, or 12K45.

[0123] In some embodiments, an antibody of the disclosure binds to its target (e.g., CD94) with any of at least 1.5-fold, at least 2-fold, at least 2.5-fold, at least 3-fold, at least 3.5-fold, at least 4-fold, at least 4.5-fold, at least 5-fold, at least 5.5-fold, at least 6-fold, at least 6.5-fold, at least 7-fold, at least 7.5-fold, at least 8-fold, at least 8.5-fold, at least 9-fold, at least 9.5-fold, at least 10-fold, or more, greater affinity than another antibody known in the art for that target.B. Exemplary Anti-CD94 Antibodies

[0124] Certain aspects of the present disclosure relate to antibodies that bind (e.g., specifically bind) to human CD94, wherein the antibodies comprise a heavy chain variable (VH) domain and a light chain variable (VL) domain. In some embodiments, the antibody is a human antibody. In some embodiments, provided herein are variants of the anti-CD94 antibody ATX-130, which is described in International Appl. No. PCT / US2021 / 052668, filed Sept. 29, 2021.

[0125] In some embodiments, the antibodies comprise a VH domain that comprises the amino acid sequence37MOFO-360690948Attorney Docket No. 18654-2001540EVQLX1ESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISX2SSX3X4IYYADS VKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDLGRYYYYMDVWGKGTTVTVS S, wherein Xi is L or V; wherein X2 is T or S; wherein X3 is N or S; and wherein X4 is F or Y (SEQ ID NO:47); and / or a VL domain that comprises the amino acid sequence DIX1MTQSPSSLSASVGDRVTITCRASQSISSWLAWX2QQKPX3KX4PKX5LIYAASSLQSGVPSX6FS GSGSGTDFTLTISSLQPEDX7ATYYCQX8YNSX9PFTFGPGTKVDIK, wherein Xi is V or Q; wherein X2is Y or F; wherein X3 is G or E; wherein X4 is A or V; wherein X5 is S or L; wherein Xe is K or R; wherein X7is V or F; wherein X8is K or Q; and wherein X9is A or Y (SEQ ID NO:48); wherein the antibody does not comprise a CDR-H1 comprising the amino acid sequence SYSMN (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence SISTSSNFIYYADSVKG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence DLGRYYYYMDV (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence RASQSISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO:5), and a CDR-L3 comprising the amino acid sequence QKYNSAPFT (SEQ ID NO:6). In some embodiments, the antibodies comprise a VH domain comprising 1, 2, 3, or 4 amino acid substitutions present in SEQ ID Nos:29-32, relative to the amino acid sequence of SEQ ID NO: 16; and / or the antibodies comprise a VL domain comprising 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions present in SEQ ID Nos:33-41, relative to the amino acid sequence of SEQ ID NO: 17.

[0126] In some embodiments, the antibodies comprise a VH domain that comprises: a CDR-H1 comprising the amino acid sequence SYSMN (SEQ ID NO: 1); a CDR-H2 comprising an amino acid sequence selected from the group consisting of SISTSSNFIYYADSVKG (SEQ ID NO: 2), SISSSSNFIYYADSVKG (SEQ ID NO: 18), SISTSSSFIYYADSVKG (SEQ ID NO: 21), and SISTSSNYIYYADSVKG (SEQ ID NO: 24); and a CDR-H3 comprising the amino acid sequence DLGRYYYYMDV (SEQ ID NO: 3); and / or a VL domain that comprises: a CDR-L1 comprising the amino acid sequence RASQSISSWLA (SEQ ID NO: 4); a CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO: 5); and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QKYNSAPFT (SEQ ID NO: 6), QQYNSAPFT (SEQ ID NO: 27), and QKYNSYPFT (SEQ ID NO: 28); wherein the antibody does not comprise a CDR-H1 comprising the amino acid sequence SYSMN (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence SISTSSNFIYYADSVKG (SEQ ID NO: 2), a CDR-H3 comprising the amino acid sequence DLGRYYYYMDV (SEQ ID NO: 3), a CDR-L1 comprising the amino acid sequence RASQSISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QKYNSAPFT (SEQ ID NO: 6).

[0127] In some embodiments, the antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence SYSMN (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence SISTSSNFIYYADSVKG (SEQ ID NO: 2), and a CDR-H3 comprising the amino acid sequence DLGRYYYYMDV (SEQ ID NO: 3). In some embodiments, the antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence SYSMN (SEQ ID NO: 1), a CDR-H2 38MOFO-360690948Attorney Docket No. 18654-2001540 comprising the amino acid sequence SISSSSNFIYYADSVKG (SEQ ID NO: 18), and a CDR-H3 comprising the amino acid sequence DLGRYYYYMDV (SEQ ID NO: 3). In some embodiments, the antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence SYSMN (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence SISTSSSFIYYADSVKG (SEQ ID NO: 21), and a CDR-H3 comprising the amino acid sequence DLGRYYYYMDV (SEQ ID NO: 3). In some embodiments, the antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence SYSMN (SEQ ID NO: 1), a CDR-H2 comprising the amino acid sequence SISTSSNYIYYADSVKG (SEQ ID NO: 24), and a CDR-H3 comprising the amino acid sequence DLGRYYYYMDV (SEQ ID NO: 3). Any of the VH domains or sets of three CDRs from a VH domain of the present disclosure may be combined with any of the VL domains or sets of three CDRs from a VL domain of the present disclosure.

[0128] In some embodiments, the VH domain further comprises: (a) a FR1 comprising an amino acid sequence selected from the group consisting of EVQLLESGGGLVKPGGSLRLSCAASGFTFS (SEQ ID NO:49) and EVQLVESGGGLVKPGGSLRLSCAASGFTFS (SEQ ID NO:50); (b) a FR2 comprising the amino acid sequence of WVRQAPGKGLEWVS (SEQ ID NO:51); (c) a FR3 comprising the amino acid sequence of RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR (SEQ ID NO:52); and (d) a FR4 comprising the amino acid sequence of WGKGTTVTVSS (SEQ ID NO:53). In some embodiments, the VH domain further comprises: (a) a FR1 comprising the amino acid sequence of EVQLLESGGGLVKPGGSLRLSCAASGFTFS (SEQ ID NO:49); (b) a FR2 comprising the amino acid sequence of WVRQAPGKGLEWVS (SEQ ID NO:51); (c) a FR3 comprising the amino acid sequence of RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR (SEQ ID NO:52); and (d) a FR4 comprising the amino acid sequence of WGKGTTVTVSS (SEQ ID NO:53). In some embodiments, the VH domain further comprises: (a) a FR1 comprising the amino acid sequence of EVQLVESGGGLVKPGGSLRLSCAASGFTFS (SEQ ID NO:50); (b) a FR2 comprising the amino acid sequence of WVRQAPGKGLEWVS (SEQ ID NO:51); (c) a FR3 comprising the amino acid sequence of RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR (SEQ ID NO:52); and (d) a FR4 comprising the amino acid sequence of WGKGTTVTVSS (SEQ ID NO:53).

[0129] In some embodiments, the antibody comprises a VL domain comprising a CDR-L1 comprising the amino acid sequence RASQSISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QKYNSAPFT (SEQ ID NO: 6). In some embodiments, the antibody comprises a VL domain comprising a CDR-L1 comprising the amino acid sequence RASQSISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQYNSAPFT (SEQ ID NO: 27). In some embodiments, the antibody comprises a VL domain comprising a CDR-L1 comprising the amino acid sequence RASQSISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QKYNSYPFT (SEQ ID NO: 28). Any of the VL domains or sets of three CDRs from a VL 39MOFO-360690948Attorney Docket No. 18654-2001540 domain of the present disclosure may be combined with any of the VH domains or sets of three CDRs from a VH domain of the present disclosure.

[0130] In some embodiments, the VL domain further comprises: (a) a FR1 comprising an amino acid sequence selected from the group consisting of DIVMTQSPSSLSASVGDRVTITC (SEQ ID NO:54) and DIQMTQSPSSLSASVGDRVTITC (SEQ ID NO: 55); (b) a FR2 comprising an amino acid sequence selected from the group consisting of WYQQKPGKAPKSLIY (SEQ ID NO:56), WFQQKPGKAPKSLIY (SEQ ID NO:57), WYQQKPEKAPKSLIY (SEQ ID NO:58), WYQQKPGKVPKSLIY (SEQ ID NO:59), and WYQQKPGKAPKLLIY (SEQ ID NO:60); (c) a FR3 comprising an amino acid sequence selected from the group consisting of GVPSKFSGSGSGTDFTLTISSLQPEDVATYYC (SEQ ID NO:61), GVPSRFSGSGSGTDFTLTISSLQPEDVATYYC (SEQ ID NO:62), and GVPSKFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO:63); and (d) a FR4 comprising the amino acid sequence of FGPGTKVDIK (SEQ ID NO:64).

[0131] In some embodiments, the VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 16 and 29-32 and / or the VL domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 17 and 33-41. In some embodiments, the antibody does not comprise a VH domain comprising the amino acid sequence of SEQ ID NO: 16 and a VL domain comprising the amino acid sequence of SEQ ID NO: 17.

[0132] In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain comprises the amino acid sequence of SEQ ID NO:33. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain comprises the amino acid sequence of SEQ ID NO:34. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain comprises the amino acid sequence of SEQ ID NO:35. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain comprises the amino acid sequence of SEQ ID NO:36. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain comprises the amino acid sequence of SEQ ID NO:37. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain comprises the amino acid sequence of SEQ ID NO:38. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain comprises the amino acid sequence of SEQ ID NO:39. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain comprises the amino acid sequence of SEQ ID NO:40. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain comprises the amino acid sequence of SEQ ID NO:41. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:29, and the VL domain comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:29, and the VL domain comprises the amino acid sequence of SEQ ID NO:33. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:29, and the VL domain comprises the amino acid sequence of SEQ ID NO:34. In some embodiments, the VH domain40MOFO-360690948Attorney Docket No. 18654-2001540 comprises the amino acid sequence of SEQ ID NO:29, and the VL domain comprises the amino acid sequence of SEQ ID NO:35. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:29, and the VL domain comprises the amino acid sequence of SEQ ID NO:36. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:29, and the VL domain comprises the amino acid sequence of SEQ ID NO:37. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:29, and the VL domain comprises the amino acid sequence of SEQ ID NO:38. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:29, and the VL domain comprises the amino acid sequence of SEQ ID NO:39. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:29, and the VL domain comprises the amino acid sequence of SEQ ID NO:40. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:29, and the VL domain comprises the amino acid sequence of SEQ ID NO:41. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:30, and the VL domain comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:30, and the VL domain comprises the amino acid sequence of SEQ ID NO:33. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:30, and the VL domain comprises the amino acid sequence of SEQ ID NO:34. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:30, and the VL domain comprises the amino acid sequence of SEQ ID NO:35. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:30, and the VL domain comprises the amino acid sequence of SEQ ID NO:36. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:30, and the VL domain comprises the amino acid sequence of SEQ ID NO:37. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:30, and the VL domain comprises the amino acid sequence of SEQ ID NO:38. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:30, and the VL domain comprises the amino acid sequence of SEQ ID NO:39. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:30, and the VL domain comprises the amino acid sequence of SEQ ID NO:40. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:30, and the VL domain comprises the amino acid sequence of SEQ ID NO:41. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:31, and the VL domain comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:31, and the VL domain comprises the amino acid sequence of SEQ ID NO:33. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:31, and the VL domain comprises the amino acid sequence of SEQ ID NO:34. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:31, and the VL domain comprises the amino acid sequence of SEQ ID NO:35. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:31, and the VL domain comprises the amino acid sequence of SEQ ID NO:36. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:31, and the VL domain comprises the amino acid sequence of SEQ ID NO:37.41MOFO-360690948Attorney Docket No. 18654-2001540In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:31, and the VL domain comprises the amino acid sequence of SEQ ID NO:38. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:31, and the VL domain comprises the amino acid sequence of SEQ ID NO:39. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:31, and the VL domain comprises the amino acid sequence of SEQ ID NO:40. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:31, and the VL domain comprises the amino acid sequence of SEQ ID NO:41. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:32, and the VL domain comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:32, and the VL domain comprises the amino acid sequence of SEQ ID NO:33. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:32, and the VL domain comprises the amino acid sequence of SEQ ID NO:34. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:32, and the VL domain comprises the amino acid sequence of SEQ ID NO:35. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:32, and the VL domain comprises the amino acid sequence of SEQ ID NO:36. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:32, and the VL domain comprises the amino acid sequence of SEQ ID NO:37. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:32, and the VL domain comprises the amino acid sequence of SEQ ID NO:38. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:32, and the VL domain comprises the amino acid sequence of SEQ ID NO:39. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:32, and the VL domain comprises the amino acid sequence of SEQ ID NO:40. In some embodiments, the VH domain comprises the amino acid sequence of SEQ ID NO:32, and the VL domain comprises the amino acid sequence of SEQ ID NO:41.

[0133] In some embodiments, an antibody of the disclosure comprises a VH domain comprising 1, 2, or 3 CDRs from a single VH domain listed in Table 1 and / or a VL domain comprising 1, 2, or 3 CDRs from a single VL domain listed in Table 1. In some embodiments, an antibody of the disclosure comprises a VH domain comprising 1, 2, or 3 CDRs from a single VH domain listed in Table 2 and / or a VL domain comprising 1, 2, or 3 CDRs from a single VL domain listed in Table 2. In some embodiments, an antibody of the disclosure comprises a VH and / or VL domain listed in Table 2. As illustrated below and described herein, in some embodiments, any set of 3 VH CDRs shown in Table 1 can be combined with any set of 3 VL CDRs shown in Table 1 in an antibody of the present disclosure. In some embodiments, any set of 3 CDRs from a VH domain shown in Table 2 can be combined with any set of 3 CDRs from a VL domain shown in Table 2 in an antibody of the present disclosure. In some embodiments, any VH domain shown in Table 2 can be combined with any VL domain shown in Table 2 in an antibody of the present disclosure.42MOFO-360690948Attorney Docket No. 18654-2001540Table 1. Anti-CD94 antibody CDR sequences43MOFO-360690948Attorney Docket No. 18654-200154044MOFO-360690948Attorney Docket No. 18654-200154045MOFO-360690948Attorney Docket No. 18654-2001540Table 2. Anti-CD94 antibody variable domain sequences46MOFO-360690948Attorney Docket No. 18654-2001540

[0134] Many definitions for CDR sequences of an antibody variable domain are known in the art and may be used to describe an antibody of the present disclosure, e.g., by CDR sequences. In some embodiments, antibody CDR sequences are defined as in Kabat (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991). In some embodiments, antibody CDR sequences are defined as in Chothia (see, e.g., Chothia and Lesk J. Mol. Biol. 196:901-917 (1987)). In some embodiments, antibody CDR sequences are defined as in IMGT (see, e.g., Lefranc, M.P. (1999) The Immunologist 1: 132-136). In some embodiments, CDR sequences of a single antibody are defined as by mixing two or more definitions, e.g., Kabat, Chothia, and / or IMGT.

[0135] In some embodiments, the VH domain comprises: a CDR-H1 comprising the amino acid sequence GFTFSSYS (SEQ ID NO: 7); a CDR-H2 comprising an amino acid sequence selected from the group consisting of ISTSSNFI (SEQ ID NO: 8), ISSSSNFI (SEQ ID NO: 19), ISTSSSFI (SEQ ID NO: 22), and ISTSSNYI (SEQ ID NO: 25); and a CDR-H3 comprising the amino acid sequence ARDLGRYYYYMDV (SEQ ID NO: 9); and / or the VL domain comprises: a CDR-L1 comprising the amino acid sequence QSISSW (SEQ ID NO: 10); a CDR-L2 comprising the amino acid sequence AAS (SEQ ID NO: 11); and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QKYNSAPFT (SEQ ID NO: 12), QQYNSAPFT (SEQ ID NO: 27), and QKYNSYPFT (SEQ ID NO: 28); wherein the antibody does not comprise a CDR-H1 comprising the amino acid sequence GFTFSSYS (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence ISTSSNFI (SEQ ID NO: 8), a CDR-H3 comprising the amino acid sequence ARDLGRYYYYMDV (SEQ ID NO: 9), a CDR-L1 comprising the amino acid sequence QSISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence AAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QKYNSAPFT (SEQ ID NO: 12).47MOFO-360690948Attorney Docket No. 18654-2001540In some embodiments, the antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence GFTFSSYS (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence ISTSSNFI (SEQ ID NO: 8), and a CDR-H3 comprising the amino acid sequence ARDLGRYYYYMDV (SEQ ID NO: 9). In some embodiments, the antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence GFTFSSYS (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence ISSSSNFI (SEQ ID NO: 19), and a CDR-H3 comprising the amino acid sequence ARDLGRYYYYMDV (SEQ ID NO: 9). In some embodiments, the antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence GFTFSSYS (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence ISTSSSFI (SEQ ID NO: 22), and a CDR-H3 comprising the amino acid sequence ARDLGRYYYYMDV (SEQ ID NO: 9). In some embodiments, the antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence GFTFSSYS (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence ISTSSNYI (SEQ ID NO: 25), and a CDR-H3 comprising the amino acid sequence ARDLGRYYYYMDV (SEQ ID NO: 9). In some embodiments, the antibody comprises a VL domain comprising a CDR-L1 comprising the amino acid sequence QSISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence AAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QKYNSAPFT (SEQ ID NO: 12). In some embodiments, the antibody comprises a VL domain comprising a CDR-L1 comprising the amino acid sequence QSISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence AAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QQYNSAPFT (SEQ ID NO: 27). In some embodiments, the antibody comprises a VL domain comprising a CDR-L1 comprising the amino acid sequence QSISSW (SEQ ID NO: 10), a CDR-L2 comprising the amino acid sequence AAS (SEQ ID NO: 11), and a CDR-L3 comprising the amino acid sequence QKYNSYPFT (SEQ ID NO: 28).

[0136] In some embodiments, the VH domain comprises: a CDR-H1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 13); a CDR-H2 comprising an amino acid sequence selected from the group consisting of STSSNF (SEQ ID NO: 14), SSSSNF (SEQ ID NO: 20), STSSSF (SEQ ID NO: 23), and STSSNY (SEQ ID NO: 26); and a CDR-H3 comprising the amino acid sequence DLGRYYYYMDV (SEQ ID NO: 15); and / or the VL domain comprises: a CDR-L1 comprising the amino acid sequence RASQSISSWLA (SEQ ID NO: 4); a CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO: 5); and a CDR-L3 comprising an amino acid sequence selected from the group consisting of QKYNSAPFT (SEQ ID NO: 6), QQYNSAPFT (SEQ ID NO: 27), and QKYNSYPFT (SEQ ID NO: 28); wherein the antibody does not comprise a CDR-H1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence STSSNF (SEQ ID NO: 14), a CDR-H3 comprising the amino acid sequence DLGRYYYYMDV (SEQ ID NO: 15), a CDR-L1 comprising the amino acid sequence RASQSISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QKYNSAPFT (SEQ ID NO: 6). In some embodiments, the antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence 48MOFO-360690948Attorney Docket No. 18654-2001540STSSNF (SEQ ID NO: 14), and a CDR-H3 comprising the amino acid sequence DLGRYYYYMDV (SEQ ID NO: 15). In some embodiments, the antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence SSSSNF (SEQ ID NO: 20), and a CDR-H3 comprising the amino acid sequence DLGRYYYYMDV (SEQ ID NO: 15). In some embodiments, the antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence STSSSF (SEQ ID NO: 23), and a CDR-H3 comprising the amino acid sequence DLGRYYYYMDV (SEQ ID NO: 15). In some embodiments, the antibody comprises a VH domain comprising a CDR-H1 comprising the amino acid sequence GFTFSSY (SEQ ID NO: 13), a CDR-H2 comprising the amino acid sequence STSSNY (SEQ ID NO: 26), and a CDR-H3 comprising the amino acid sequence DLGRYYYYMDV (SEQ ID NO: 15). In some embodiments, the antibody comprises a VL domain comprising a CDR-L1 comprising the amino acid sequence RASQSISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QKYNSAPFT (SEQ ID NO: 6). In some embodiments, the antibody comprises a VL domain comprising a CDR-L1 comprising the amino acid sequence RASQSISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QQYNSAPFT (SEQ ID NO: 27). In some embodiments, the antibody comprises a VL domain comprising a CDR-L1 comprising the amino acid sequence RASQSISSWLA (SEQ ID NO: 4), a CDR-L2 comprising the amino acid sequence AASSLQS (SEQ ID NO: 5), and a CDR-L3 comprising the amino acid sequence QKYNSYPFT (SEQ ID NO: 28).

[0137] In some embodiments, an antibody of the disclosure comprises an Fc region. In some embodiments, the Fc region is a human IgGl Fc region. In some embodiments, the antibody comprises a human Fc region that is non-fucosylated. In some embodiments, the antibody binds to a human cellular Fc gamma receptor IIIA to a greater extent than an antibody comprising a wild type human IgGl Fc region. In some embodiments, the antibody is capable of inducing antibody-dependent cellular cytotoxicity (ADCC) against a cell expressing human CD94 on its surface.

[0138] In some embodiments, the anti-CD94 antibody comprises an antibody heavy chain comprising the amino acid sequence of EVQLLESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISTSSNFIYYADSVK GRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDLGRYYYYMDVWGKGTTVTVSSASTKGPSV FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS SLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTP EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:65) and / or an antibody light chain comprising the amino acid sequence of DIVMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKSLIYAASSLQSGVPSKFSGSG 49MOFO-360690948Attorney Docket No. 18654-2001540SGTDFTLTISSLQPEDVATYYCQKYNSAPFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVV CLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT HQGLSSPVTKSFNRGEC (SEQ ID NO:66). In some embodiments, the anti-CD94 antibody comprises an antibody heavy chain comprising the amino acid sequence of SEQ ID NO:65 and an antibody light chain comprising the amino acid sequence of SEQ ID NO:66. In some embodiments, the antibody heavy chain comprises the amino acid sequence of SEQ ID NO:65 with a C-terminal lysine. In some embodiments, the antibody heavy chain is non-fucosylated.

[0139] In some embodiments, the term antibody is used in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments so long as they exhibit the desired antigen-binding activity. In some embodiments, an antibody of the disclosure is an isolated antibody. An "isolated" antibody is one which has been identified and separated and / or recovered from a component of its natural environment. Contaminant components of its natural environment are materials which would interfere with research, diagnostic, and / or therapeutic uses for the antibody, and may include enzymes, hormones, and other proteinaceous or nonproteinaceous solutes. In some embodiments, an antibody is purified (1) to greater than 95% by weight of antibody as determined by, for example, the Lowry method, and in some embodiments, to greater than 99% by weight; (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of, for example, a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under reducing or nonreducing conditions using, for example, Coomassie blue or silver stain. An isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody's natural environment will not be present. Ordinarily, however, an isolated antibody will be prepared by at least one purification step.

[0140] In some embodiments, a monoclonal antibody is an antibody obtained from a population of substantially homogeneous antibodies, z.e., the individual antibodies comprising the population are identical and / or bind the same epitope, except for possible variant antibodies, e.g., containing naturally occurring mutations or arising during production of a monoclonal antibody preparation, such variants generally being present in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen. Thus, in some embodiments, a monoclonal antibody is obtained from a substantially homogeneous population of antibodies. Monoclonal antibodies may be produced using any method known in the art. For example, monoclonal antibodies to be used in accordance with the present disclosure may be made by a variety of techniques, including but not limited to the hybridoma method, recombinant DNA methods, phagedisplay methods, and methods utilizing transgenic animals containing all or part of the human immunoglobulin loci.C. Blocking ofHLA-E binding50MOFO-360690948Attorney Docket No. 18654-2001540

[0141] Major histocompatibility complex class I, E (HLA-E) is the ligand of the CD94 / NKG2A heterodimer and plays a crucial role in the inhibition of NK cell and CD8+ T cell activity when bound to the CD94 / NKG2A heterodimer. Thus, without wishing to be bound to theory, blocking HLA-E and CD94 / NKG2A interaction may result in activation and proliferation of target cells, e.g., cells expressing CD94. Thus, it may be beneficial that an anti-CD94 antibody does not block HLA-E interaction with the CD94 / NKG2A heterodimer, e.g., in a subject with an NK / T cell lymphoma administered the anti-CD94 antibody. In some embodiments, HLA-E is human HLA-E, also known as QA1 and HLA-6.2. For an exemplary HLA-E gene, see, e.g., NCBI Gene ID No. 3133; for an exemplary HLA-E polypeptide, see, e.g., NP_005507.3.

[0142] In some embodiments, blocking of binding of HLA-E to the CD94 / NKG2A heterodimer refers to blocking of binding of HLA-E to the CD94 / NKG2A heterodimer, blocking of binding of HLA-E to CD94, and / or blocking of binding of HLA-E to NKG2A.

[0143] Blocking of binding of HLA-E to the CD94 / NKG2A heterodimer by an antibody of the disclosure may be assessed using any method known in the art. For example, blocking of binding of HLA- E to the CD94 / NKG2A heterodimer by an antibody of the disclosure may be assessed using an ex vivo assay using PBMCs and / or NK cells, e.g., as described in the Examples. In an exemplary assay, PBMCs, e.g., obtained from healthy donors, are incubated with human Fc block (Biolegend, San Diego, CA) and cell viability dye (Thermo Fisher, Carlsbad, CA) for 30 minutes on ice and protected from light. Cells are then washed once with FACS buffer (PBS with 2% IgG low FBS). Anti-CD94 antibodies or isotype control antibodies at saturating concentrations are incubated with the cells for 30 minutes on ice and protected from light. Cells are then washed and incubated with HLA-E tetramer PE (Creative Biolabs, Shirley, NY), CD3 pacific blue, and CD56 FITC antibodies (Biolegend, San Diego, CA) for 30 minutes on ice and protected from light. Cells then receive a final wash in FACS buffer before quantification on a flow cytometer. Data acquisition and fluorescence compensation may be performed using methods known in the art, such as using a CytoFlex flow cytometer (Beckman Coulter, Chaska, MN). Data analysis may be performed using any method known in the art, such as using the FlowJo software. NK cells are identified through gating on lymphocytes on the forward and side scatter, followed by doublet and dead cell exclusion, and gated on the CD3-CD56+ population. HLA-E is then quantified on the CD3-CD56+ NK cell population. Percent blocking of binding of HLA-E to the CD94 / NKG2A heterodimer by an anti- CD94 antibody compared to a control antibody, e.g., an isotype control antibody, is calculated as: 100 - ((percent HLA-E positive for anti-CD94 antibody ) / (percent HLA-E positive for isotype)* 100).

[0144] In some embodiments, an antibody blocks binding of HLA-E to the CD94 / NKG2A heterodimer if it blocks more than about 20% of HLA-E binding to the CD94 / NKG2A heterodimer, e.g., compared to an isotype control antibody. In some embodiments, an antibody blocks binding of HLA-E to the CD94 / NKG2A heterodimer if it blocks about 21%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%,51MOFO-360690948Attorney Docket No. 18654-2001540 about 90%, about 95%, about 99%, or 100% of HLA-E binding to the CD94 / NKG2A heterodimer, e.g., compared to an control antibody, e.g., an isotype control antibody

[0145] In some embodiments, an antibody does not block binding of HLA-E to the CD94 / NKG2A heterodimer if it blocks about 20% or less of HLA-E binding to the CD94 / NKG2A heterodimer, e.g., compared to an isotype control antibody. In some embodiments, an antibody does not block binding of HLA-E to the CD94 / NKG2A heterodimer if it blocks about 20%, about 18%, about 16%, about 14%, about 12%, about 10%, about 8%, about 6%, about 4%, about 2%, about 1%, about 0.5%, or 0% of HLA- E binding to the CD94 / NKG2A heterodimer, e.g., compared to an control antibody, e.g., an isotype control antibody.

[0146] In some embodiments, an antibody provided herein does not block binding of HLA-E to the CD94 / NKG2A heterodimer. In some embodiments, an antibody provided herein blocks about 20% or less, about 19% or less, about 18% or less, about 17% or less, about 16% or less, about 15% or less, about 14% or less, about 13% or less, about 12% or less, about 11% or less, about 10% or less, about 9% or less, about 8% or less, about 6% or less, about 5% or less, about 4% or less, about 3% or less, about 2% or less, about 1% or less, about 0.5% or less, or 0% of binding of HLA-E to the CD94 / NKG2A heterodimer, compared to a control antibody, e.g., an isotype control antibody. In some embodiments, an antibody provided herein blocks 0% of binding of HLA-E to the CD94 / NKG2A heterodimer, compared to a control antibody, e.g., an isotype control antibody.D. Enhanced ADCC Activity

[0147] In some embodiments, antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular cytotoxicity, antibody directed cell cytotoxicity, or ADCC refer to a cell-mediated reaction in which non-specific cytotoxic cells producing Fc receptors, e.g. natural killer cells (NK cells), neutrophils, and macrophages, recognize an antibody bound to a target cell and then cause lysis of the target cell. The primary mediator cells are natural killer (NK) cells. NK cells express FcyRIII (Ravetch et al. (1991) Annu. Rev. Immunol., 9:457-92). In some embodiments, ADCC activity refers to the ability of an antibody or Fc fusion protein to elicit an ADCC reaction.

[0148] In some embodiments, the antibodies provided herein have enhanced antibody-dependent cellular cytotoxicity (ADCC) activity. In some embodiments, enhanced ADCC activity refers to an antibody or an Fc region of an antibody mediating or inducing ADCC more efficiently and / or more effectively than a native or wild type antibody and / or a native or wild type Fc region of an antibody in the presence of effector cells in vitro or in vivo, which may be determined using an ADCC assay, e.g., as described herein or as is commonly known in the art. In some embodiments, effector cells are leukocytes that produce one or more Fc receptors and perform effector functions. In some embodiments, such cells produce at least FcyRIII and perform the ADCC effector function. Examples of ADCC-mediated human leukocytes include peripheral blood mononuclear cells (PBMCs), natural killer cells (NK), monocytes, cytotoxic T cells, and neutrophils.52MOFO-360690948Attorney Docket No. 18654-2001540

[0149] In some embodiments, ADCC activity can be assessed directly using an in vitro assay, using a51Cr release assay using peripheral blood mononuclear cells (PBMC) and / or NK effector cells, see e.g., Shields et al. (2001) J. Biol. Chem., 276:6591-6604, or another suitable method. ADCC activity may be expressed as the number of remaining cells following an ADCC assay, or a concentration of antibody or Fc fusion protein at which the lysis of target cells is half-maximal (e.g., EC50 or IC50). In some embodiments, ADCC activity is determined using an ex vivo assay using PBMCs and / or NK cells, and the ADCC activity of an antibody of the disclosure is described as the percent of target cells remaining after the ADCC assay and / or the IC50 or EC50 of the antibody (i.e., the concentration of an antibody of the disclosure at which half the maximum target cell depletion or cell lysis is achieved). The IC50 or EC50 of an antibody may be determined using any method known in the art, e.g., using a dosage response curve and GraphPad Prism.

[0150] In some embodiments, the antibodies provided herein induce ADCC activity with an IC50 or EC50 measured using an ex vivo assay of between about 1 ng / ml to about 100 ng / ml (e.g., any of about 1 ng / ml, about 2 ng / ml, about 3 ng / ml, about 4 ng / ml, about 5 ng / ml, about 10 ng / ml, about 15 ng / ml, about 20 ng / ml, about 25 ng / ml, about 30 ng / ml, about 35 ng / ml, about 40 ng / ml, about 45 ng / ml, about 50 ng / ml, about 55 ng / ml, about 60 ng / ml, about 65 ng / ml, about 70 ng / ml, about 75 ng / ml, about 80 ng / ml, about 85 ng / ml, about 90 ng / ml, about 95 ng / ml, or about 100 ng / ml). In some embodiments, the antibodies provided herein induce ADCC activity with an IC50 or EC50 measured using an ex vivo assay of about 20 ng / ml or less. In some embodiments, the antibodies provided herein induce ADCC activity with an IC50 or EC50 measured using an ex vivo assay of about 60 ng / ml or less. In some embodiments, an antibody of the disclosure exhibits an IC50 or EC50 that is at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% lower than the IC50 or EC50 of a control antibody (e.g., a wild type control antibody, or an antibody known in the art or commercially available against the same target).

[0151] In some embodiments, IC50 or EC50 refers to the concentration of a compound (e.g., an antibody) which induces a response halfway between the baseline and maximum after a specified exposure time. For example, IC50 or EC50 may be used to measure the potency of an antibody for mediating and / or inducing an effector function, e.g., ADCC activity. In some embodiments, the IC50 or EC50 of a dose response curve represents the concentration of a compound (e.g., an antibody) where 50% of its maximal effect is observed.

[0152] In some embodiments, an antibody of the disclosure has a higher maximal target cell lysis compared to a control antibody (e.g., a wild type control antibody, or an antibody known in the art or commercially available against the same target). For example, antibodies of the disclosure may exhibit a maximal target cell lysis that is at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100% higher than53MOFO-360690948Attorney Docket No. 18654-2001540 that of a control antibody (e.g., a wild type control antibody, or an antibody known in the art or commercially available against the same target).(i) Enhanced Binding to Fc Receptors

[0153] In some embodiments, the antibodies provided herein include a human immunoglobulin Fc region that has enhanced ADCC activity compared to a wild type Fc region. In some embodiments, the antibodies provided herein bind to a human cellular Fc receptor to a greater extent than an antibody comprising a wild type Fc region. In some embodiments, an Fc receptor (FcR) is a receptor that is capable of binding to an Fc region of an antibody. Certain Fc receptors can bind to IgG (i.e., y-receptor); such receptors include subclasses of FcyRI, FcyRII and FcyRIII, as well as their allelic variants and alternative splicing events. For an overview of the Fc receptors see Ravetch and China: Annu. Port. Immunol. 9, 457 (1991); Capel et al. hnmunomethods, 4, 25 (1994); and de Haas et al., J. Leg. Clin. Med. 126, 330 (1995).

[0154] In some embodiments, the antibodies provided herein bind to a human cellular Fc gamma receptor IIIA to a greater extent than an antibody comprising a wild type Fc region. In some embodiments, the human cellular Fc gamma receptor IIIA comprises a valine residue or a phenylalanine residue at amino acid residue position 158. See, e.g., UniProt Accession P08637 or VAR_003960. In some embodiments, the human cellular Fc gamma receptor IIIA comprises the sequence of SEQ ID NO: 45 or 46.Human cellular Fc gamma receptor IIIA 158FMWQLLLPTALLLLVSAGMRTEDLPKAVVFLEPQWYRVLEKDSVTLKCQGA YSPEDNSTQWFHNESLISSQASSYFIDAATVDDSGEYRCQTNLSTLSDPV QLEVHIGWLLLQAPRWVFKEEDPIHLRCHSWKNTALHKVTYLQNGKGRKY FHHNSDFYIPKATLKDSGSYFCRGLFGSKNVSSETVNITITQGLAVSTIS SFFPPGYQVSFCLVMVLLFAVDTGLYFSVKTNIRSSTRDWKDHKFKWRKD PQDK ( SEQ ID NO : 45 )Human cellular Fc gamma receptor IIIA 158VMWQLLLPTALLLLVSAGMRTEDLPKAVVFLEPQWYRVLEKDSVTLKCQGA YSPEDNSTQWFHNESLISSQASSYFIDAATVDDSGEYRCQTNLSTLSDPV QLEVHIGWLLLQAPRWVFKEEDPIHLRCHSWKNTALHKVTYLQNGKGRKY FHHNSDFYIPKATLKDSGSYFCRGLVGSKNVSSETVNITITQGLAVSTIS SFFPPGYQVSFCLVMVLLFAVDTGLYFSVKTNIRSSTRDWKDHKFKWRKD PQDK ( SEQ ID NO : 46 )

[0155] In some embodiments, an antibody provided herein is of the IgG (e.g., IgGl, IgG2, IgG3, or IgG4), IgA (IgAl or IgA2), IgD, IgM, or IgE isotype. In some embodiments, an antibody provided herein is of the IgG, isotype. In some embodiments, an antibody provided herein is of the IgGl, isotype. In some embodiments, antibodies provided herein bind to a human cellular Fc gamma receptor IIIA (FcyRIIIA) to 54MOFO-360690948Attorney Docket No. 18654-2001540 a greater extent than an antibody comprising a wild type human IgGl Fc region. In some embodiments, the human cellular Fc gamma receptor IIIA comprises a valine residue or a phenylalanine residue at amino acid residue position 158. Exemplary assays for determining binding to a human cellular Fc gamma receptor IIIA are known in the art; see, e.g., Lazar, G.A. et al. (2006) Proc. Natl. Acad. Sci. 103:4005-1010; and Ferrara, C. et al. (2011) roc. Natl. Acad. Sci. 108: 12669-12674.

[0156] In some embodiments, an Fc region is a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. In some embodiments, an Fc region includes a native Fc region or a variant Fc region. In one embodiment, a human IgG heavy chain Fc region extends from Cys226, or from Pro230, to the carboxyl -terminus of the heavy chain. However, the C-terminal lysine (Lys447) of the Fc region may or may not be present. In some embodiments, a full-length antibody of the present disclosure may or may not comprise the C-terminal lysine. In some embodiments, numbering of amino acid residues in an Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991. In some embodiments, a wild type Fc region or a native Fc region are an Fc region that comprises an amino acid sequence that is identical to the amino acid sequence of the Fc region found in nature. In some embodiments, a variant Fc region is an Fc region that comprises an amino acid sequence that differs from the native or wild type sequence of the Fc region in at least one amino acid. In some embodiments, a variant Fc region has at least one amino acid substitution, e.g., approximately 1-10 or 1-5 amino acid substitutions. In some embodiments, the Fc region variant is at least approximately 80% (e.g., at least about 90%, or at least about 95%) homologous to a native or wild type sequence Fc region and / or an Fc region of an original polypeptide. In some embodiments, the at least one amino acid substitution in the variant Fc region enhances the effector function of the variant Fc region compared to a native or wild type Fc region. In some embodiments, an effector function is a biological activity attributable to the Fc region of an antibody, which vary with the antibody isotype. Examples of antibody effector functions include: Clq binding and complement dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); antibody-dependent cell-mediated phagocytosis (ADCP); down regulation of cell surface receptors (e.g., B-cell receptor); and B-cell activation.

[0157] The binding affinity of an antibody for an Fc receptor may be assessed using any method known in the art, such as using surface plasmon resonance, and / or ELISA, e.g., as described in Shields et al. (2001) J. Biol. Chem., 276:6591-6604. In some embodiments, the affinity of an antibody of the disclosure for FcyRIIIA may be above that of the wild-type control by any of at least about 1.5-fold, at least about 2-fold, at least about 3 -fold, at least about 4-fold, at least about 5 -fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold, at least about 10-fold, at least about 20 fold, at least about 30-fold, at least about 40-fold, at least about 50-fold, or higher.

[0158] In some embodiments, affinity refers to the strength of the sum total of noncovalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen or a 55MOFO-360690948Attorney Docket No. 18654-2001540 target). For example, the affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (KD). Affinity can be measured by common methods known in the art, including those described herein.

[0159] In some embodiments, statements that a molecule (e.g., an antibody and / or an Fc region) binds to a greater extent than another molecule (e.g., an antibody and / or an Fc region), or that a molecule (e.g., an antibody and / or an Fc region) binds with a greater affinity than another molecule (e.g., an antibody and / or an Fc region), or other grammatical equivalents, refer to a molecule (e.g., an antibody and / or an Fc region) binding more tightly (e.g., having a lower dissociation constant) to a target (e.g., an Fc receptor, a cell surface protein) than another molecule (e.g., an antibody and / or an Fc region) in binding assays (e.g., as described herein and / or as commonly known in the art) under substantially the same conditions. For example, the statement that an antibody “X” binds to an Fc receptor to a greater extent than an antibody “Y” indicates that antibody “X” binds more tightly (e.g., has a lower dissociation constant) to an Fc receptor than antibody “Y” in binding assays (e.g., as described herein and / or as commonly known in the art) under substantially the same conditions. In another example, the statement that an antibody “X” binds to a target (e.g., a cell surface protein, such as CD94) with a greater affinity than an antibody “Y” indicates that antibody “X” binds more tightly (e.g., has a lower dissociation constant) to a target (e.g., a cell surface protein, such as CD94) than antibody “Y” in binding assays (e.g., as described herein and / or as commonly known in the art) under substantially the same conditions.(ii) Reduced Fucosylation

[0160] In some embodiments, an antibody of the present disclosure is non-fucosylated or fucose- deficient, e.g., a glycosylation antibody variant comprising an Fc region wherein a carbohydrate structure attached to the Fc region has reduced fucose or lacks fucose. In some embodiments, an antibody with reduced fucose or lacking fucose has improved ADCC function. Non-fucosylated or fucose-deficient antibodies have reduced fucose relative to the amount of fucose on the same antibody produced in a cell line. In some embodiments, a non-fucosylated or fucose-deficient antibody composition of the present disclosure is a composition in which less than about 50% of the N-linked glycans attached to the Fc region of the antibodies in the composition comprise fucose.

[0161] In some embodiments, fucosylation or fucosylated refers to fucose residues within the oligosaccharides attached to the peptide backbone of an antibody of the present disclosure. Specifically, a fucosylated antibody comprises a (l,6)-linked fucose at the innermost N-acetylglucosamine (GlcNAc) residue in one or both of the N-linked oligosaccharides attached to the antibody Fc region, e.g., at position Asn 297 of the human IgGl Fc domain (EU numbering of Fc region residues). Asn297 may also be located about + 3 amino acids upstream or downstream of position 297, i.e., between positions 294 and 300, due to minor sequence variations in immunoglobulins.

[0162] In some embodiments, a degree of fucosylation is a percentage of fucosylated oligosaccharides relative to all oligosaccharides, e.g., as identified by methods known in the art, such as in an N- glycosidase F treated antibody composition assessed by matrix-assisted laser desorption-ionization time- 56MOFO-360690948Attorney Docket No. 18654-2001540 of-flight mass spectrometry (MALDI-TOF MS). In a composition of a fully fucosylated antibody, at least 90% or essentially all oligosaccharides comprise fucose residues, i.e. are fucosylated. Accordingly, an individual antibody in such a composition typically comprises fucose residues in each of the two N-linked oligosaccharides in the Fc region. In some embodiments, in a composition of a fully non-fucosylated antibody, less than about 10% or essentially none of the oligosaccharides are fucosylated, and an individual antibody in such a composition does not contain fucose residues in either of the two N-linked oligosaccharides in the Fc region. In a composition of a partially fucosylated antibody, only part of the oligosaccharides comprise fucose. An individual antibody in such a composition can comprise fucose residues in none, one or both of the N-linked oligosaccharides in the Fc region, provided that the composition does not comprise essentially all individual antibodies that lack fucose residues in the N- linked oligosaccharides in the Fc region, nor essentially all individual antibodies that contain fucose residues in both of the N- linked oligosaccharides in the Fc region. In one embodiment, a composition of a partially fucosylated antibody has a degree of fucosylation of about 10% to about 80% (e.g., about 50% to about 80%, about 60% to about 80%, or about 70% to about 80%).

[0163] In some embodiments, a glycosylation antibody variant comprises an Fc region, wherein a carbohydrate structure attached to the Fc region lacks fucose. Such variants have improved ADCC function. Examples of defucosylated or fucose-deficient antibodies are described in: US 2003 / 0157108; WO 2000 / 61739; WO 2001 / 29246; US 2003 / 0115614; US 2002 / 0164328; US 2004 / 0093621; US 2004 / 0132140; US 2004 / 0110704; US 2004 / 0110282; US 2004 / 0109865; WO 2003 / 085119; WO 2003 / 084570; WO 2005 / 035586; WO 2005 / 035778; W02005 / 053742; Okazaki et al. J. Mol. Biol. 336: 1239-1249 (2004); Yamane-Ohnuki et al. Biotech. Bioeng. 87: 614 (2004).

[0164] Antibodies with reduced fucosylation, or antibodies that are non-fucosylated may be produced using any method known in the art. In some embodiments of the antibodies of the disclosure, at least one or two of the heavy chains of the antibody can be non-fucosylated. For example, antibodies of the disclosure with reduced fucosylation, or antibodies of the disclosure that are non-fucosylated may be produced in a cell line having a alphal,6-fucosyltransferase (Fut8) knockout, and / or overexpressing [31,4- N-acetylglycosminyltransferase III (GnT-III), and / or overexpressing Golgi p-mannosidase II (Manll). Antibodies with reduced fucosylation, or antibodies that are non-fucosylated may also be generated using a cell line that is deficient for 'FUT8', alpha- 1,6 fucosyltransferase, which catalyzes the transfer of fucose; using Chinese hamster ovary (CHO) cells, e.g., that are deficient in FUT8 (Y amane-Ohnuki et al., 2004); or using small interfering RNAs (siRNAs) to block the expression of the FUT8 gene (Mori et al., 2004). Other cell lines that may be used to produce non-fucosylated or defucosylated antibodies or antibodies with reduced fucosylation are known in the art, e.g., include Eecl3 CHO cells deficient in protein fucosylation (Ripka et al. Arch. Biochem. Biophys. 249:533-545 (1986); US Pat Appl No US 2003 / 0157108 Al, Presta, E; and WO 2004 / 056312 Al, Adams et al., especially at Example 11), and knockout cell lines, such as alpha- 1,6-fucosyltransferase gene, FUT8, knockout CHO cells (Yamane-57MOFO-360690948Attorney Docket No. 18654-2001540Ohnuki et al. Biotech. Bioeng. 87: 614 (2004)), and cells overexpressing [31,4-N- acetylglycosminyltransferase III (GnT-III) and Golgi p-mannosidase II (Manll).

[0165] In some embodiments, antibodies of the present disclosure have reduced fucose relative to the amount of fucose on the same antibody produced in a wild-type CHO cell. For example, an antibody can have a lower amount of fucose than it would otherwise have if produced by native CHO cells (e.g., a CHO cell that produce a native glycosylation pattern, such as, a CHO cell containing a native FUT8 gene). In some embodiments, an antibody provided herein is one wherein less than about 50%, 40%, 30%, 20%, 10%, 5% or 1% of the N-linked glycans thereon comprise fucose. In certain embodiments, an antibody provided herein is one wherein none of the N-linked glycans thereon comprise fucose, i.e., wherein the antibody is completely without fucose, or has no fucose, or is non-fucosylated, or is afiicosylated. The amount of fucose can be determined by one of skill in the art, e.g., by calculating the average amount of fucose within the sugar chain at Asn297, relative to the sum of all glycostructures attached to Asn297 (e.g., complex, hybrid and high mannose structures) as measured by MALDI-TOF mass spectrometry, as described in WO 2008 / 077546, for example. Asn297 refers to the asparagine residue located at about position 297 in the Fc region (Eu numbering of Fc region residues); however, Asn297 may also be located about ± 3 amino acids upstream or downstream of position 297, i.e., between positions 294 and 300, due to minor sequence variations in antibodies. In some embodiments, at least one or two of the heavy chains of the antibody is non-fucosylated.

[0166] Antibodies lacking 1,6-fiicose on their heavy chain glycosylation may have enhanced binding affinity to the FcyRIII receptor and increased ADCC activity (see, e.g., Shields et al., 2002; Shinkawa et al, 2002; Okazaki, 2004; Dall'Ozzo, 2004). In some embodiments, the antibodies provided herein include an Fc region with modifications including reduced fucosylation, non-fiicosylation, and / or mutations that enhance ADCC activities and / or improve affinity of the Fc region for Fc receptors such as FcyRIII and CD16 (e.g., CD16a). In some embodiments, the molecules (e.g., the antibodies provide herein) induce antibody directed cell cytotoxicity (ADCC) and deplete or reduce the number of NK cells and / or T cells that express CD94 to a higher extent over a fucosylated or wild type antibody.

[0167] In some embodiments, an antibody of the disclosure is engineered to improve ADCC activity by reducing fucosylation. In some embodiments, the molecules provided herein (e.g., the antibodies provided herein) can induce antibody directed cell cytotoxicity (ADCC) and deplete or reduce number of NK cells and / or T cells that express CD94 to a higher extent than a fucosylated or wild type antibody. In some embodiments, at least one or two of the heavy chains of an antibody of the disclosure are non-fucosylated. In some embodiments, an antibody of the disclosure is modified such that the carbohydrates of the antibody are non-fucosylated. In some embodiments, an antibody of the disclosure is modified such that less than about 90%, e.g., less than any of about 90%, about 80%, about 70%, about 60%, about 50%, about 40%, about 30%, about 20%, about 10%, about 5%, or about 1%, of the carbohydrates of the antibody contain fucose. In some embodiments, an antibody of the disclosure is modified such that less58MOFO-360690948Attorney Docket No. 18654-2001540 than about 40% of the carbohydrates of the antibody contain fucose. In some embodiments, the antibodies provided herein are non-fucosylated.

[0168] In some embodiments, the molecules (e.g., antibodies) provided herein induce antibody directed cell cytotoxicity (ADCC) and deplete or reduce the number of NK cells and / or T cells that express CD94 to a higher extent over a fucosylated or wild type antibody.(Hi) Mutations that Enhance ADCC Activity

[0169] An antibody of the disclosure may comprise a variant Fc region. In some embodiments, the variant Fc region includes at least one amino acid substitution in the Fc region that improves ADCC activity. For example, an antibody of the disclosure may have a variant IgGl Fc region which comprises one or more of the Fc mutations selected from S239D, A330L, I332E, F243L and G236A. In another example, an antibody of the disclosure may have a human IgGl Fc variant region which comprises one or more of the Fc mutations selected from S239D, A330L, I332E, F243L and G236A. Other amino acid substitutions that are known to enhance ADCC activity may be used, for example, as described in Lazar et al., PNAS 103, 4005-4010 (2006); Shields et al., J. Biol. Chem. 276, 6591-6604 (2001); Stewart et al., Protein Engineering, Design and Selection 24, 671-678 (2011), and Richards et al., Mol Cancer Ther 7, 2517-2527 (2008).(iv) Reduced Internalization

[0170] In some embodiments, an antibody of the disclosure has a low degree of internalization, e.g., receptor-induced internalization or target internalization (i.e., internalization of surface expressed CD94), e.g., as compared to a wild type control antibody, or an antibody known in the art or commercially available for the same target. Antibodies with lower internalization have a higher receptor (e.g., CD94) occupancy on the cell surface and higher level of the receptor-antibody complexes on the cell surface, which may enhance ADCC activity. An antibody of the disclosure may be tested in vitro for its internalization capabilities. An antibody of the disclosure may be tested in an ex vivo assay, e.g., using PBMCs and / or NK cells, for its internalization capabilities, e.g., as described in the Examples. The internalization of the target (e.g., CD94) may be expressed as the percent decrease in mean fluorescence intensity (MFI) over a period of time using a flow cytometry-based assay, e.g., as described in the Examples. For example, the internalization of the target (i.e., the internalization capabilities of an antibody of the disclosure) may be expressed as the percent decrease in MFI, calculated by computing the difference in MFI over a 24 hour period (e.g., between 0.5 and 24 hours) in cells incubated with the antibody at 37 degrees Celsius, and multiplying by 100, e.g., as described in the Examples.

[0171] In some embodiments, an antibody has a high degree of internalization if it results in an MFI decrease of greater than 50%, calculated by computing the difference in MFI over a 24 hour period (e.g., between 0.5 and 24 hours) in cells incubated with antibody at 37°C, and multiplying by 100, as measured by an ex vivo assay, e.g., using PBMCs and / or NK cells, as described in the Examples. In some embodiments, an antibody has a high degree of internalization if incubating the antibody with a cell expressing human CD94 on its surface for 24 hours at 37°C results in a decrease in surface antibody 59MOFO-360690948Attorney Docket No. 18654-2001540 staining of greater than 50% due to internalization, assessed using methods known in the art and / or as described above.

[0172] In some embodiments, an antibody has a low degree of internalization if it results in an MFI decrease of less than 50% (e.g., any of about 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, 5% or less, 1% or less, or 0%), calculated by computing the difference in MFI over a 24 hour period (e.g., between 0.5 and 24 hours) in cells incubated with antibody at 37°C, and multiplying by 100, as measured by an ex vivo assay, e.g., using PBMCs and / or NK cells, as described in the Examples. In some embodiments, an antibody of the disclosure has a low degree of internalization and results in an MFI decrease of about 50% or less, about 40% or less, about 35% or less, about 30% or less, about 25% or less, about 20% or less, about 15% or less, about 10% or less, about 5% or less, about 2.5% or less, about 1% or less, or about 0%, calculated as described above. In some embodiments, an antibody has a low degree of internalization if incubating the antibody with a cell expressing human CD94 on its surface for 24 hours at 37°C results in a decrease in surface antibody staining of less than 50% due to internalization, assessed using methods known in the art and / or as described above.

[0173] In some embodiments, an antibody of the disclosure has or results in internalization activity that is at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 99%, or about 100% lower the internalization of a control antibody, e.g., a commercial or wild type control antibody, or an isotype control antibody, wherein internalization is assessed as described above and / or using any suitable method known in the art.

[0174] Antibody candidates with no or low internalization activity may be further tested for binding to a target from cynomolgus monkeys and / or from humans (e.g., cynomolgus and / or human CD94). Antibodies that bind to a cynomolgus monkey and / or human target may be used for cell killing assays (e.g., ADCC assays) in vitro and in vivo. The cell killing activity (e.g., ADCC activity) of the selected antibodies may be compared to the commercially available antibodies or antibodies known in the art.E. Generation of Antibodies

[0175] An antibody of the disclosure may be generated using any technologies and / or methods known in the art. Techniques for preparing antibodies, e.g., monoclonal antibodies (mAbs), against virtually any target antigen are well known in the art. See, for example, Kohler and Milstein, Nature 256: 495 (1975), and Coligan et al. (eds ), CURRENT PROTOCOLS IN IMMUNOLOGY, VOL. 1, pages 2.5.1-2.6.7 (John Wiley & Sons 1991). Briefly, monoclonal antibodies can be obtained by injecting mice with a composition comprising an antigen (e.g., CD94, or a part thereof), removing the spleen to obtain B- lymphocytes, fusing the B-lymphocytes with myeloma cells to produce hybridomas, cloning the hybridomas, selecting positive clones which produce antibodies to the antigen, culturing the clones that produce antibodies to the antigen, and isolating the antibodies from the hybridoma cultures. The person of60MOFO-360690948Attorney Docket No. 18654-2001540 ordinary skill will realize that where antibodies are to be administered to human subjects, the antibodies will bind to human antigens (e.g., human CD94, or a part thereof).

[0176] MAbs can be isolated and purified from hybridoma cultures by a variety of well-established techniques. Such isolation techniques include affinity chromatography with Protein-A or Protein-G Sepharose, size-exclusion chromatography, and ion-exchange chromatography. See, for example, Coligan at pages 2.7.1-2.7.12 and pages 2.9. 1-2.9.3. Also, see Baines et al., “Purification of Immunoglobulin G (IgG),” in METHODS IN MOLECULAR BIOLOGY, VOL. 10, pages 79-104 (The Humana Press, Inc. 1992).

[0177] After the initial raising of antibodies to the immunogen (e.g., CD94, or a part thereof), the antibodies can be sequenced and subsequently prepared by recombinant techniques. Humanization and chimerization of murine antibodies and antibody fragments are well known to those skilled in the art, as discussed below.

[0178] In an exemplary method of generating an antibody of the disclosure, recombinant targets (e.g., CD94) may be utilized for immunization of mice. Antibodies generated following immunization of mice, e.g., as described above, may be analyzed for specific or selective binding to its target (e.g., CD94) by ELISA and flow cytometry. Antibodies may be selected based on their ability to bind to a target (e.g., CD94).

[0179] In some embodiments, non-human primate antibodies may be generated. General techniques for raising therapeutically useful antibodies in baboons may be found, for example, in Goldenberg et al., WO 91 / 11465 (1991), and in Losman et al., Int. J. Cancer 46: 310 (1990).

[0180] In some embodiments, an antibody may be a human antibody. In some embodiments, an antibody may be a monoclonal human antibody. In some embodiments, a human antibody possesses an amino acid sequence which corresponds to that of an antibody produced by a human or a human cell or derived from a non-human source that utilizes human antibody repertoires or other human antibodyencoding sequences. Such antibodies may be obtained from transgenic mice that have been engineered to produce specific human antibodies in response to antigenic challenge e.g., CD94, or a part thereof. Methods for producing fully human antibodies using either combinatorial approaches or transgenic animals transformed with human immunoglobulin loci are known in the art (e.g., Mancini et al., 2004, New Microbiol. 27:315-28; Conrad and Scheller, 2005, Comb. Chem. High ThroughputScreen. 8: 117-26; Brekke and Loset, 2003, Curr. Opin. Phamacol. 3:544-50). In certain embodiments, the claimed methods and procedures may utilize human antibodies produced by such techniques. Other methods of producing fully human antibodies include phage display, e.g., as described in Dantas-Barbosa et al., 2005, Genet. Mol. Res. 4: 126-40, generation of antibodies in normal humans or from humans that exhibit a particular disease state, e.g., as described in Dantas-Barbosa et al., 2005, or using transgenic animals (e.g., mice) that have been genetically engineered to produce human antibodies using standard immunization protocols as discussed above, e.g., as described in Green et al., 1999, J. Immunol.61MOFO-360690948Attorney Docket No. 18654-2001540Methods 231: 11-23, Green et al., Nature Genet. 7: 13 (1994), Lonberg et al., Nature 368:856 (1994), and Taylor et al., Int. Immun. 6:579 (1994).(i) In Vitro Cell Killing Assays

[0181] Generation of an antibody of the disclosure may involve testing the in vitro ADCC activity of the antibody. The improved cell killing or ADCC activity of an antibody of the disclosure may be tested as described above, as described in the Examples, and / or using methods known in the art. The improved cell killing or ADCC activity of an antibody of the disclosure may be tested for depletion of NK cells and / or T cells that express CD94. Depletion ofNK cells and / or T cells that express CD94 may be tested using an exemplary in vitro model that recapitulates activity in humans (Tomasevic, et al, Growth Factors, 2014; 32(6): 223-235; Huang, et al, JCI insight, 2016;l(7):e86689). Peripheral blood lymphocytes (PBL) isolated from the blood of normal (i.e., healthy) donors are incubated with antibodies that have a human Fc region with and without fucose and / or with and without Fc region mutations. The level of killing of NK cells and / or T cells that express CD94 in the PBLs (e.g., in a PBL sample) is measured using any method known in the art, such as flow cytometry (e.g., as described in the Examples). The cell killing activity (e.g., ADCC activity) of antibodies may be tested as described above, e.g., using the assay described above, using a variety of biospecimens such as blood, synovial fluid, bone marrow and spleen intact cell homogenates.

[0182] In addition to the cell killing assay described above, in vitro ADCC and antibody-dependent cellular phagocytosis (ADCP) assays using antibodies of the disclosure, purified target cells (e.g., NK cells and / or T cells that express CD94), and / or effector cells such as NK cells or monocytes / macrophages may be performed to assay the cell killing, ADCC and / or ADCP activity of antibodies of the disclosure. Cell killing, ADCC and / or ADCP assays, and other assay methods known in the art may be used, for example, as described in Koibeck et al., J Allergy Clin Immunol.2010;125(6): 1344-1353. e2; Gomez-Roman et al., J. Immunol. Methods, 2006, 308, pp. 53-67; and Ackerman et al., J. Immunol. Methods, 2011, 366, pp. 8-19. The in vitro activity of an antibody of the disclosure may be compared to a commercially available antibody or an antibody known in the art against the same target.(ii) In Vivo Cell Killing Assays

[0183] Generation of an antibody of the disclosure may involve testing the in vivo ADCC activity of the antibody, e.g., to show activity of the selected antibody candidates in vivo for depletion or reduction in the levels of NK cells and / or T cells that express CD94. The in vivo cell killing activity (e.g., ADCC and / or ADCP activity) of an antibody of the disclosure may be determined using any method known in the art. For example, the ability of an antibody of the disclosure to deplete or reduce NK cells and / or T cells that express CD94 in vivo may be tested in cynomolgus monkeys using methods known in the art. For example, in an exemplary method to test the in vivo cell killing activity (e.g., ADCC and / or ADCP activity) of an antibody of the disclosure, a cohort of cynomolgus monkeys are bled one day prior to62MOFO-360690948Attorney Docket No. 18654-2001540 administration of a single dose of an antibody of the disclosure, e.g., antibody treatment, to identify the pre-dose levels of NK cells and / or T cells that express CD94 by flow cytometry. After administration of an antibody of the disclosure, e.g., upon treatment with antibodies of the disclosure, the monkeys are bled at the following time points: 1 hour, 1 day, 7 days, 14 days and 30 days. The levels of NK cells and / or T cells that express CD94 in blood and other biospecimens such as synovial fluids, bone marrow and spleen are determined by flow cytometry at each of the time points. The in vivo activity of an antibody of the disclosure may be compared to a commercially available antibody or an antibody known in the art against the same target. An anti-CD94 antibody of the disclosure may be compared to anti-CD94 antibody clones DX22, HP-3D9, HP-3B1, 131412, or 12K45.

[0184] A skilled artisan will readily appreciate that other methods known in the art for testing ADCC activity in vivo may be used to assay the in vivo ADCC activity of antibodies of the disclosure (e.g., transgenic animals such as transgenic mice).

[0185] Other known antibodies against the target (e.g., CD94) may also be used in the methods provided herein. For example, an anti-CD94 antibody of the disclosure may be tested (e.g., for in vitro or in vivo ADCC activity, or for any other characteristic described herein) together with the following anti- CD94 antibodies: HP-3D9 (LSBio Catalog # LS-C 134679- 100; Abnova Catalog #: MAB6947); 212; 131412 (R&D Systems Catalog #: MAB1058); 13B146 (US Biological Catalog #: 030068); 13B147 (US Biological Catalog #: 030069); 1H1 (Abnova Catalog #: MAB10543); 3G2 (Biorbyt Catalog #: orb69389); DX22 (Biolegend Catalog # 305502); REA113 (Miltenyi Biotec Catalog #: 130-098-967); KP43; EPR21003; AT13E3 (ATGen Catalog: ATGA0487); HP-3B1; 12K45; and B-D49.(Hi) Humanization

[0186] An antibody of the disclosure may be humanized according to any method known in the art. In some embodiments, a humanized antibody is a chimeric antibody comprising amino acid residues from non-human hypervariable regions (HVRs) and amino acid residues from human framework regions (FRs). In certain embodiments, a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the HVRs (e.g., CDRs) correspond to those of a non-human antibody, and all or substantially all of the FRs correspond to those of a human antibody. A humanized antibody optionally may comprise at least a portion of an antibody constant region derived from a human antibody. In some embodiments, a humanized form of an antibody, e.g., a non-human antibody, refers to an antibody that has undergone humanization.

[0187] For example, a monoclonal antibody may be humanized by transferring mouse CDRs from the heavy and light variable chains of a mouse immunoglobulin into the corresponding variable domains of a human antibody. The mouse framework regions (FR) in the chimeric monoclonal antibody may also be replaced with human FR sequences. To preserve the stability and antigen specificity of the humanized monoclonal antibody, one or more human FR residues may be replaced by the mouse counterpart residues. Humanized monoclonal antibodies may be used for therapeutic treatment of subjects.Techniques for the production of humanized monoclonal antibodies are well known in the art, e.g., as 63MOFO-360690948Attorney Docket No. 18654-2001540 described in Jones et al., 1986, Nature, 321:522; Riechmann et al., Nature, 1988, 332:323; Verhoeyen et al., 1988, Science, 239: 1534; Carter et al., 1992, Proc. Nat'l Acad. Sci. USA, 89:4285; Sandhu, Crit. Rev. Biotech., 1992, 12:437; Tempest et al., 1991, Biotechnology 9:266; Singer et al., J. Immun., 1993, 150:2844.

[0188] An antibody of the disclosure may have one or more of the characteristics described above, e.g., enhanced in vitro and / or in vivo cell killing activity (e.g., ADCC and / or ADCP activity), enhanced binding to one or more Fc receptors, reduced fucosylation or non-fucosylation, cross-reactivity (e.g., binding to human CD94 and to cynomolgus monkey CD94), lack of blocking of HLA-E binding to the CD94 / NKG2A heterodimer, competition with commercially available antibodies (e.g., commercially available anti-CD94 antibodies), low internalization, and / or desirable affinity for its target protein (e.g., CD94, human CD94, and / or cynomolgus CD94).

[0189] In some embodiments, an antibody of the disclosure is soluble at concentrations higher than about lOmg / mL. In some embodiments, an antibody of the disclosure forms a low level of soluble aggregates (e.g., less than 5%, less than 4%, less than 3%, less than 2%, or less than 1% soluble aggregates). In some embodiments, an antibody of the disclosure has an ability to maintain binding to its target (e.g., CD94) during storage, e.g., for at least 1 week, at least 2 weeks, at least 3 weeks, at least 1 month, at least 2 months, at least 3 months, at least 4 months, or more, at any of about 2°C, about 3°C, about 4°C, about 5°C, about 6°C, about 7°C, about 8°C. In some embodiments, an antibody of the disclosure has stability (e.g., lack of degradation products, e.g., as measured by SDS-PAGE) during storage, e.g., for at least 1 week, at least 2 weeks, at least 3 weeks, at least 1 month, at least 2 months, at least 3 months, at least 4 months, or more, at any of about 2°C, about 3 °C, about 4°C, about 5 °C, about 6°C, about 7°C, or about 8°C.

[0190] In some embodiments, an antibody of the disclosure is tested for toxicology. Toxicology analysis of an antibody of the disclosure may be carried out using any method known in the art. In an exemplary toxicology analysis, an antibody of the disclosure is tested for toxicity in cynomolgus monkeys at doses that are more than 5 times higher (e.g., any of about 5 times higher, about 10 times higher, about 15 times higher, about 20 times higher, about 25 times higher, about 30 times higher, about 35 times higher, about 40 times higher, about 45 times higher, about 50 times higher, about 55 times higher, about 60 times higher, about 65 times higher, about 70 times higher, about 75 times higher, about 80 times higher, about 85 times higher, about 90 times higher, about 95 times higher, about 100 times higher, or more) than the doses anticipated to be used in human subjects.

[0191] In some embodiments, an antibody of the disclosure is capable of depleting or reducing the level of NK cells and / or T cells that express CD94 in vitro and / or in vivo. Depletion or reduction in the level of NK cells and / or T cells that express CD94 may be measured using any method known in the art. For example, depletion of NK cells and / or T cells that express CD94 may be measured using a cell killing, ADCC, and / or ADCP assay, e.g., as described above and / or as described in the Examples.64MOFO-360690948Attorney Docket No. 18654-2001540

[0192] In some embodiments, an antibody of the disclosure is soluble at concentrations higher than lOmg / mL, has low level of soluble aggregates (<5%), maintains its binding to the target as measured by ELISA (>90% potency), with no degradation products as measured by SDS PAGE when incubated for 3 months at 2-8°C. In some embodiments, toxicology analysis of an antibody of the disclosure can be performed in cynomolgus monkeys at doses that are more than 5 times higher than the doses anticipated to be used in human subjects.

[0193] In some embodiments, the antibodies that bind to CD94 may deplete or reduce the level of NK cells and / or T cells that express CD94 and may have clear benefits for patients (e.g., human patients) with autoimmune diseases or disorders such as rheumatoid arthritis (RA), Felty’s syndrome, inclusion body myositis, alopecia areata (AA), vitiligo (VT), and lichen planus (LP). In some embodiments, the LP is cutaneous or oral LP.IV Pharmaceutical Formulations

[0194] In some embodiments, an antibody of the disclosure is administered as part of a pharmaceutical composition or formulation, e.g., comprising the antibody and one or more pharmaceutically acceptable carriers. In some embodiments, a pharmaceutical composition, a composition, or a pharmaceutical formulation refer to a biologically active compound (e.g., an antibody of the disclosure), optionally mixed with at least one pharmaceutically acceptable chemical component, such as, though not limited to carriers, stabilizers, diluents, dispersing agents, suspending agents, thickening agents, excipients and the like.

[0195] Pharmaceutical compositions, pharmaceutical formulations, and / or compositions of any of the antibodies of the disclosure for use in any of the methods as described herein may be prepared by mixing such antibody having the desired degree of purity with one or more optional pharmaceutically acceptable carriers (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the form of lyophilized formulations or aqueous solutions.

[0196] Pharmaceutically acceptable carriers are generally nontoxic to recipients at the dosages and concentrations employed, and include, but are not limited to: buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride; benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; saltforming counter-ions such as sodium; metal complexes (e.g., Zn-protein complexes); and / or non-ionic surfactants such as polyethylene glycol (PEG). Exemplary pharmaceutically acceptable carriers herein65MOFO-360690948Attorney Docket No. 18654-2001540 further include insterstitial drug dispersion agents such as soluble neutral-active hyaluronidase glycoproteins (sHASEGP), for example, human soluble PH-20 hyaluronidase glycoproteins, such as rHuPH20 (HYLENEX®, Baxter International, Inc.). Certain exemplary sHASEGPs and methods of use, including rHuPH20, are described in US Patent Publication Nos. 2005 / 0260186 and 2006 / 0104968. In one aspect, a sHASEGP is combined with one or more additional glycosaminoglycanases such as chondroitinases.

[0197] The formulation herein may also contain more than one active ingredient as necessary for the particular indication (e.g., a disease or disorder) being treated, preferably those with complementary activities that do not adversely affect each other.

[0198] Active ingredients may be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatinmicrocapsules and poly-(methylmethacylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles and nanocapsules) or in macroemulsions. Such techniques are disclosed in Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980).

[0199] Sustained-release preparations may be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody or immunoconjugate, which matrices are in the form of shaped articles, e.g., fdms, or microcapsules.

[0200] The formulations to be used for in vivo administration are generally sterile. Sterility may be readily accomplished, e.g., by filtration through sterile filtration membranes.K Kits and Articles of Manufacture

[0201] In another aspect of the disclosure, a kit or an article of manufacture containing materials useful for the methods provided herein, e.g., treatment of the autoimmune diseases or disorders described above, are provided.

[0202] In some embodiments, the kit or article of manufacture comprises one or more doses of an anti- CD94 antibody of the present disclosure, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg. In some embodiments, the kit or article of manufacture comprises a container comprising one or more doses of an anti-CD94 antibody of the present disclosure, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg. For example, in some embodiments, each of the one or more doses is 24mg of the antibody. In some embodiments, each of the one or more doses is 80mg of the antibody. In some embodiments, each of the one or more doses is 240mg of the antibody. In some embodiments, each of the one or more doses is 450mg of the antibody. In some embodiments, the one or more doses of the antibody are provided in container. In some embodiments, the anti-CD94 antibody is dibotatug. In some embodiments, the kit or article of manufacture is for use in the treatment of an autoimmune described herein, e.g., an autoimmune66MOFO-360690948Attorney Docket No. 18654-2001540 disease or disorder selected from Felty’s syndrome, rheumatoid arthritis (RA), inclusion body myositis, alopecia areata (AA), lichen planus (e.g., cutaneous lichen planus, oral lichen planus, esophageal lichen planus, lichen planopilaris (LPP), or another form of lichen planus disclosed herein or known in the art) or vitiligo (VT). For example, in some embodiments, the LP is cutaneous or oral LP.

[0203] In some embodiments, the kit or article of manufacture may comprise a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, IV solution bags, etc. The containers may be formed from a variety of materials such as glass or plastic. The container holds a composition which is by itself or combined with another composition effective for the methods provided herein, e.g., treatment of the autoimmune diseases or disorders described above, and may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). At least one active agent in the composition is an antibody of the disclosure.

[0204] The label or package insert indicates that the composition is used for the methods provided herein, e.g., treatment of the autoimmune diseases or disorders described above in a subject. In some embodiments, the package insert comprises instructions for administering the antibody or composition according to any of the methods disclosed herein. In some embodiments, the instructions are for administering the antibody to an individual in need thereof at one or more doses of 24mg, 80mg, 240mg, or 450mg, e.g., as described herein. In some embodiments, the one or more doses are the same dose selected from 24mg, 80mg, 240mg, and 450mg.

[0205] Moreover, the kit or article of manufacture may comprise (a) a first container with a composition contained therein, wherein the composition comprises an antibody of the disclosure; and (b) a second container with a composition contained therein, wherein the composition comprises a further therapeutic agent. The kit or article of manufacture in this embodiment of the invention may further comprise a package insert indicating that the compositions can be used to treat a particular autoimmune disease or disorder, e.g., as described herein. Alternatively, or additionally, the kit or article of manufacture may further comprise a second (or third) container comprising a pharmaceutically-acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution or dextrose solution. It may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, and syringes.

[0206] The following description is presented to enable a person of ordinary skill in the art to make and use the various embodiments. Descriptions of specific devices, techniques, and applications are provided only as examples. Various modifications to the examples described herein will be readily apparent to those of ordinary skill in the art, and the general principles defined herein may be applied to other examples and applications without departing from the spirit and scope of the various embodiments. Thus, the various embodiments are not intended to be limited to the examples described herein and shown, but are to be accorded the scope consistent with the claims.67MOFO-360690948Attorney Docket No. 18654-2001540EXAMPLESExample 1: A Pilot Safety and Clinical Activity Phase lb Study of Anti-CD94 Antibody in Adults with Alopecia Areata or Vitiligo or Lichen PlanusRationale

[0207] AA is an autoimmune disease characterized by non-scarring hair loss of the scalp and other hairbearing areas of the body. A large meta-analysis, including 300 million subjects, estimated the global prevalence of AA as 2.11% of the global population (Lee, H.H. et al. (2020) J Am Acad Dermatol. 82(3):675-682). Until recently there were no US Food and Drug Administration (FDA) -approved treatments for AA, and a variety of approaches were used, including contact irritants, contact immunotherapy, corticosteroids, prostaglandins, vitamin D / analogs, immunosuppressives such as cyclosporine, tacrolimus, azathioprine, methotrexate, minoxidil, antihistamines, hydroxychloroquine, aprimilast, HMG-CoA reductase inhibitors, anti-IL4 / 13 (e.g., duplimumab), anti-IL-17 (e.g., secukinumab), platelet rich plasma, and laser and light therapy (Lepe, K. et al. , PMID 30725685; Sibbald, C. (2023) J Cutan Med Surg. 27(3):241-259). The effectiveness of these treatments varies, especially for severe disease. Recently, two orally administered Janus kinase (JAK) inhibitors have been approved for AA: baricitinib (OLUMIANT™) and ritlecitinib (LITFULO™). Both drugs have black box warnings including serious infections leading to hospitalization, tuberculosis (TB), lymphoma / other malignancies, and thrombosis. In addition, the ritlecitinib warning includes all-cause mortality, major adverse cardiac events, and serious infections leading to death. In the registration studies, the proportion of patients who had >80% scalp hair regrowth was 15 to 16% better at Week 36 in patients who received baricitinib at 2mg / day compared with placebo and 21.4% better at Week 24 for patients who received ritlecitinib at 50mg / day. The safety concerns and efficacy profile of FDA -approved therapies suggest there is still an unmet need in this area. In particular, a targeted biologic immunotherapy such as anti-CD94 antibody may offer a favorable risk / benefit.

[0208] VT is a depigmenting skin disorder resulting from autoimmune loss of melanocytes leading to loss of pigment in the affected areas of the skin (Bergqvist, C. et al. (2020) Dermatology 236(6) :571-592). VT is the most common skin depigmenting disease and affects 0.5 to 2% of the population globally. For stable non-segmental (NSV) disease, topical treatment with corticosteroids or calcineurin inhibitors are used as first-line therapy (Frisoli, M.L. et al. (2020) Annu Rev Immunol. 38:621-648) and typically 2-3 months of therapy are given before response is evaluated. Second-line treatments are phototherapy with narrowband ultraviolet B or psoralen with ultraviolet A and systemic steroids. For rapidly progressing disease, systemic steroids are given. In July 2022 ruxolitinib (JAK1 / 2 inhibitor; OPZELURA™) topical cream was approved for “non-segmental vitiligo in adults and adolescents aged 12 and upward,” originally approved in 2011 for atopic dermatitis. Despite the topical delivery in VT the label carries black box warnings of the risk of serious infections, mortality, and malignancy from the oral delivery68MOFO-360690948Attorney Docket No. 18654-2001540 forms of the drug. This suggests that there is potential for a targeted biologic immunotherapy, such as anti-CD94 antibody, which may have a favorable risk / benefit profde.

[0209] Cytotoxic or terminal effector CD8 T cells are thought to play pathological roles in the development of autoimmune diseases such as alopecia areata (AA) and vitiligo (VT) (Gleave, A. et al. (2023) Biomolecules 13(2):388; Frisoli, M.L. et al. (2020) Annu Rev Immunol. 38:621-648; Xing, L. et al. (2 A) Nat. Med. 20(9): 1043-1049; Lee, E.Y. et al. (2023) Proc Natl Acad Sci USA 120(29):e2305764120; Harris, J.E. et al. (2012) J Invest Dermatol. 132(7): 1869-1876). A body of evidence suggests that these CD8 T cells are elevated by 2- to 3-fold in blood and diseased skin compared to healthy individuals (Lee, E.Y. et al. (2023) Proc Natl Acad Sci USA 120(29):e2305764120; Nigam, P.K. et al. (2011) Indian J Dermatol Venereol Leprol. 77(1): 111). These CD8 T cells are clonally expanded, proximal to the tissue site where damage occurs, and produce granzyme B and IFNy (Gellatly,K.J. et al. (2021) Sci Transl Med. 13(610):eabd8995; de Jong, A. et al. (2018) JCI Insight. 3(19):el21949; Nigam, P.K. et al. (2011) Indian J Dermatol Venereol Leprol. 77(1): 111; Xing, L. et al. (2014) Nat. Med. 20(9): 1043-1049; Turk, L. et al. (2024) Front. Immunol. 15: 1285798; Takahashi, R. et al. (2024) J Invest Dermatol. S0022-202X(24):25-3; van den Boom, J.G. et al. (2009) J Invest Dermatol. 129(9):2220- 2232). These cells are known to be activated upon antigen encounter and play a direct role in destruction of melanocytes and hair follicles in AA and VT (Gleave, A. et al. (2023) Biomolecules 13(2):388; Frisoli, M.L. et al. (2020) Annu Rev Immunol. 38:621-648).

[0210] Cytotoxic CD8+ T cells are thought to be the major producers of IFNy and granzyme B in AA and VT. In vivo studies of IFNy inhibition in AA and VT mouse models demonstrated reversible hair loss and skin re-pigmentation upon IFNy blockade (Harris, J.E. et al. (2012) J Invest Dermatol. 132(7): 1869- 1876; Xing, L. et al. (2014) Nat. Med. 20(9): 1043-1049). Furthermore, responders to Janus kinase (JAK) inhibitors in clinical studies of AA not only experienced hair regrowth 12 weeks post treatment, but also suppression of granzyme B+ CD8 T cells (Xing, L. et al. (2014) Nat. Med. 20(9): 1043-1049). From bulk and single-cell RNA-sequencing studies, CD94 is upregulated by 2.8-fold in lesional skin of AA patients and is significantly increased in blood and lesional skin of VT patients relative to healthy controls (Xing,L. et al. (2 A) Nat. Med. 20(9): 1043-1049; Gellatly, K.J. et al. (2021) Sci Transl Med.13(610):eabd8995; Subramanya, R.D. et al. (2010) Genomics 96(3): 146-153).

[0211] Taken together, CD94 is highly expressed in AA and VT skin lesions and is positively correlated with granzyme B and IFNy expression on the pathological CD8+ T cells. In addition, given the association between IFNy / granzyme B levels in the skin and disease severity (Koguchi-Yoshioka, H. et al. (2021) J Invest Dermatol. 141(2):427-429.el0; Ng, C.Y. et al. (2022) Front Immunol. 13:872458), CD94 may also contribute to disease severity in AA and VT. These preclinical findings, along with the recent approval of JAK inhibitors in these diseases (OLUMIANT® or baricitinib, LITFULO® or ritlecitinib, OPZELURA® or ruxolitinib) suggest that anti-CD94 antibody treatment has the potential to eliminate pathologic CD8 T cells and may bring clinical benefit in AA and VT patients.69MOFO-360690948Attorney Docket No. 18654-2001540

[0212] LP is a chronic, inflammatory disease that can involve the skin, oral mucosa, genitals, nails, esophagus, and other areas. It is difficult to treat with 30-50% being refractory to current therapies (Passeron et al. Br J Dermatol 2024; 00: 1-11), and LP frequently has significant impacts on quality of life, as symptoms associated with LP include intense pruritus and pain. In addition, LP may lead to longterm or permanent effects, depending on the site involved, including scarring and hair loss (for cutaneous forms), nail disfigurement (when nails are involved), and esophageal strictures (for esophageal LP). No well-controlled RCT has demonstrated efficacy, and typical first-line therapy consists of corticosteroids (topical, intralesional, or systemic, depending on the extent and type of LP), but corticosteroids are well- known to cause various toxicities and adverse effects that can be local (e.g., skin atrophy) or systemic (e.g., cataracts, bone density loss, skin changes, susceptibility to infections, etc.). Thus, there is an unmet medical need for safe, more effective therapies.

[0213] As shown by biopsies of active LP lesions (e.g., skin biopsy for cutaneous LP), histopathology is typified by a set of characteristic pathologic findings including a dense lymphocytic infiltrate at the dermal-epidermal junction, and cytotoxic CD8+ T cells directed against basal keratinocytes are thought to play a central role (Lehman et al. Int J Dermatol. 2009;48(7):682). These cytotoxic cells are depleted in circulation and in tissue by DR-01, a novel molecule that is being developed in several indications (vitiligo, alopecia areata, cytotoxic T-cell and NK-cell lymphomas, and LGL leukemia) and has been discovered by the Applicant to be active in cutaneous disease, as demonstrated by its early efficacy in cytotoxic T-cell lymphomas, many of which involve the skin.

[0214] Applicant has discovered that the anti-CD94 antibody dibotatug, also known as DR-01, can safely deplete pathogenic, autoreactive cytotoxic cell types in the skin and other tissues. Based at least in part on this discovery, treatment of LP patients with DR-01 is expected to be safe, effective, and steroid- sparing. The clinical investigation described in this Example 1, to demonstrate safety, PK, PD, and preliminary efficacy in LP highlights the utility for DR-01 in the treatment of cutaneous lichen planus and other forms of lichen planus, including, but not limited to, Oral Lichen Planus, Cutaneous Lichen Planus, Esophageal Lichen Planus, Genital Lichen Planus, Lichen Planopilaris, Nail Lichen Planus, Lichen Planus Pigmentosus, Hypertrophic Lichen Planus, Bullous Lichen Planus, and Inverse Lichen Planus. Forms of Lichen Planus are well known in the art, and are reviewed, e.g., in Boch et al. (Boch et al. Lichen Planus. Front Med (Lausanne). 2021 Nov 1 ;8: 737813) and Weston et al. (Int J Womens Dermatol. 2015 Aug; 1(3): 140-149).

[0215] This Example describes a phase lb study on the safety and clinical activity of dibotatug (also known as DR-01) treatment in adults with AA or VT or LP (e.g., cutaneous lichen planus or lichen planopilaris or mucosal / oral, genital, esophageal, otic, or nail lichen planus).Objectives and Endpoints70MOFO-360690948Attorney Docket No. 18654-2001540

[0216] A primary objective of this study (for both AA and VT) is to evaluate the safety and tolerability of the anti-CD94 antibody (dibotatug) in adults with AA or VT. The primary endpoints for this objective are adverse events (AEs), vital signs, and clinical laboratory values.

[0217] A primary objective of this study for AA is to explore the effect of the anti-CD94 antibody (dibotatug) on AA disease activity measures at Week 24. The primary endpoint for this objective is the mean change from baseline in Severity of Alopecia Tool (SALT) score.

[0218] A primary objective of this study for VT is to explore the effect of the anti-CD94 antibody (dibotatug) on VT disease activity measures at Week 24. The primary endpoint for this objective is the mean change from baseline in vitiligo area scoring index (VASI).

[0219] A secondary objective of this study (for both AA and VT) is to characterize the pharmacokinetics (PK) of the anti-CD94 antibody (dibotatug). The secondary endpoints for this objective are anti-CD94 antibody (dibotatug) concentrations in blood over time and derived PK parameters including maximum observed concentration (Cmax), trough concentration (Ctrough), area under the concentration time curve (AUC), and half-life (ti / 2).

[0220] Another secondary objective of this study (for both AA and VT) is to evaluate the immunogenicity of the anti-CD94 antibody (dibotatug). The secondary endpoints for this objective are incidence and persistence of anti-drug antibodies (ADAs) in blood.

[0221] For LP, endpoints include overall response by Physician Global Assessment (PGA) of skin with treatment response defined as PGA 0 to 3 (with > 50% score reduction), changes in modified CAILS (mCAILS), total body lesion count, affected BSA, pruritus numeric rating scale (NRS), pruritus verbal rating scale (VRS), pruritus visual analog scale (VAS), pain NRS, and Skindex-16.Study Design

[0222] This is a 48-week, parallel-group, open-label, randomized Phase lb study to explore the safety and clinical activity of the anti-CD94 antibody (dibotatug) in adults with AA or VT or LP. An overview of the study design is provided in FIG. 1.

[0223] Each subject’s participation in the study includes the following periods:• Screening: up to 28 days• Treatment period: Day 1 to Week 24• Safety follow-up (SFU) period: Week 24 to 48

[0224] Subjects with AA or VT or LP may be eligible for the study and may enter screening after providing signed informed consent. After having satisfied applicable disease-specific and general inclusion and exclusion criteria, approximately 80 subjects are randomized at a ratio of 1: 1: 1: 1 to one of the following 4 fixed-dose arms:• Anti-CD94 antibody (dibotatug), 24mg• Anti-CD94 antibody (dibotatug), 80mg• Anti-CD94 antibody (dibotatug), 240mg71MOFO-360690948Attorney Docket No. 18654-2001540• Anti-CD94 antibody (dibotatug), 450mg

[0225] Subjects are stratified 1 : 1 : 1 : 1 by disease so that the number of AA and VT and LP subjects in each arm is balanced with approximately equal numbers of subjects per arm. For VT, the proportion of subjects with active and stable disease in each arm is balanced by stratification. Similarly, for AA, the proportion of subjects with severe and moderate disease in each arm is balanced by stratification. Subjects who discontinue prior to Week 24 may be replaced. Anti-CD94 antibody (dibotatug) is administered on Day 1, Day 8, Day 15, Week 4, then once every 4 weeks as described below, with the last dose being given at Week 20.

[0226] Anti-CD94 antibody (dibotatug) is administered IV on Day 1, Day 8, Day 15, Week 4, then once every 4 weeks to Week 20.

[0227] For the first dose of anti-CD94 antibody only, all subjects receive corticosteroid (e.g., methylprednisolone 80mg or equivalent) intravenous (IV) at least 60 minutes (and no more than 3 hours) prior to infusion. This is performed at Day 1 and Day 2 of the split first dose. Prior to every dose of anti- CD94 antibody, all subjects receive premedication, which includes an antipyretic (e.g., acetaminophen 650-1000mg) and antihistamine (e.g., diphenhydramine 50mg) orally (PO) at least 30 minutes (and no more than 3 hours) prior to infusion. For subjects not experiencing any infusion-related reactions (IRRs), premedication may be tapered as follows. For Day 1 and Day 2, premedications include antihistamine PO, antipyretic PO, and corticosteroid IV. For Days 8 and 15 and Weeks 4, 8, and 12, premedications include antihistamine PO and antipyretic PO. For Weeks 16 and 20, premedications may continue to be weaned per Investigator judgement if subject has never experienced an IRR or may continue to use 2 drug premedication throughout.

[0228] The first dose of anti-CD94 antibody (dibotatug) is administered over 2 days with lOmg being given on Day 1, and the remainder of the dose being given on Day 2. Subsequent doses are given as a single infusion. If a subject is unable to receive the entire dose as a single infusion, the remaining volume needed to complete the entire dose is administered the following day (i.e., the entire dose can be administered over 2 sequential days).

[0229] The entire dose of anti-CD94 antibody (dibotatug) is administered over approximately 4 hours. If no Grade 2 or higher IRR occurs, the infusion time can be reduced as follows. For Day 1 and Day 2, infusion time is ~4 hours with 3 hours post-dose observation. For Day 8 and Day 15, infusion time is ~3 hours with 2 hours post-dose observation. For Week 4 and all subsequent doses, infusion time is ~2 hours with 2 hours post-dose observation.

[0230] For LP subjects, disease assessments every 2-4 weeks will be conducted throughout the study. Assessments will include photography, investigator assessments, and patient-reported outcome measures. PD will be assessed by skin biopsy changes and measurements taken from these biopsies (e.g., immunostaining, cytokine measurements, quantification of cytotoxic and other cell types).Subject Eligibility Criteria72MOFO-360690948Attorney Docket No. 18654-2001540

[0231] General inclusion criteria include:• Age > 18 with the ability to understand and comply with protocol-required study procedures and voluntarily sign written informed consent document• Women of childbearing potential must agree to use a highly effective method of contraception from enrollment through at least 20 weeks after last dose of the anti-CD94 antibody (dibotatug)• Male subjects must agree to use acceptable effective method(s) of contraception from enrollment through at least 20 weeks after last dose of the anti-CD94 antibody (dibotatug)

[0232] Alopecia areata-specific inclusion criteria include:• Diagnosed with moderate to severe AA with > 20% scalp hair loss at screening, according to SALT (Olsen, E. et al. (1999) J am Acad Dermatol. 40(2 Pt l):242-246)• Current episode of AA lasting from > 6 months to < 10 years prior to screening• No spontaneous improvement in the 6 months prior to screening or between screening and baseline (decrease in SALT score of < 10, > 10 would be an improvement)• Patients with a current episode of AA lasting for > 10 years may participate if there was regrowth in affected areas of the scalp over the 10 years prior to screening• Agree not to use any AA treatments during the study (exception: chronic treatment with bimatoprost ophthalmic solution for eyelashes and chronic treatment with 5 alpha reductase inhibitors, oral or topical minoxidil)• Agree not to use adhesive wigs (other than banded perimeter wig) during the study• Be willing to maintain the same hair style and hair dyeing throughout the study period. Subjects who shave their scalp must be willing to refrain from shaving their scalp for at least 2 weeks prior to each SALT assessment. Hair trimming outside the treatment areas to maintain the current hair style is permitted.

[0233] Vitiligo-specific inclusion criteria include:• Have active or stable non-segmental VT at screening and baseline defined as follows: o Clinical diagnosis of non-segmental VT for at least 3 months; and o Body surface area (BSA) involvement 4% to 60% excluding involvements at palms of the hands, dorsal aspect of fingers and thumbs including metacarpophalangeal joints, soles of the feet, or dorsal aspect of the feet; and o BSA > 0.25% involvement on the face excluding involvement at vermilion (confirmed by photographs at screening); and o Subjects with active VT should have at least 1 active lesion defined as 1 of the following:■ New / extending lesion(s) in the past 3 months (confirmed by photographs or medical record);■ Confetti-like lesion(s);■ Trichrome lesion(s);73MOFO-360690948Attorney Docket No. 18654-2001540■ Koebner phenomenon / phenomena (excluding Type 1 [history based isomorphic reaction]); o Coexistence of halo nevus / nevi (also known as Sutton nevus / nevi) is permitted• If receiving concomitant medications for any reason other than VT, must be on a stable regimen, which is defined as not starting a new drug or changing dosage within 7 days or 5 half-lives (whichever is longer) prior to Day 1. Subject must be willing to stay on a stable regimen during the duration of the study.• Must agree to follow the usual and habitual exposure to sunlight and not change the use of sunblock and not use tanning booths, sun lamps, or other ultraviolet light sources other than provided / requested by the study team during the study.

[0234] General exclusion criteria include the following. Subjects meeting any of the following criteria are ineligible.• Participation in an investigational drug or device trial in which administration of an investigational drug or device occurred within 28 days or 5 half-lives of screening, whichever is shorter• Use of live vaccines during the study and within 28 days prior to screening• Known history of chronic alcohol abuse, IV drug abuse, or illicit drug abuse within 1 year before screening• Diagnosis or history of malignant disease within 5 years prior to baseline, with the exceptions of basal cell or squamous epithelial carcinomas of the skin that have been resected or cervical carcinoma in situ, with no evidence of recurrence within the 5 years prior to baseline• Any surgical procedure (except for minor surgery requiring local or no anesthesia and without any complications or sequelae) within 12 weeks prior to screening, or any planned surgical procedure scheduled to occur during the study• Any of the following types of infection within 28 days of screening or before randomization: o Serious (requiring hospitalization and / or IV anti-infective treatment) o Chronic (duration of symptoms, signs, and / or treatment of 6 weeks or longer) o Viral reactivation of cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella-zoster virus (VZV) or herpes simplex virus type (HSV) infection requiring systemic therapy in the last 2 years• Any of the following: o Human immunodeficiency virus (HIV) infection o Current infection with hepatitis B virus (HBV) (i.e., positive for hepatitis B surface antigen and / or polymerase chain reaction positive for HBV DNA) o Current infection with hepatitis C virus (HCV) (i.e., positive for HCV RNA)74MOFO-360690948Attorney Docket No. 18654-2001540• Concurrent diagnosis of history of any autoimmune diseases other than AA or VT requiring systemic or topical immunotherapy• Use of topical and oral JAK inhibitors within 4 and 8 weeks of randomization, respectively• Use of lymphocyte depleting agents (e.g., rituximab, ocrelizumab, ofatumumab, ublituximab, thymoglobulin, alemtuzumab, etc.) within 6 months of screening or until lymphocyte counts have normalized• Use of other biologies within 4 weeks of screening• Use of oral immune suppressants (e.g., cyclosporine A, azathioprine, methotrexate, sulfasalazine, systemic corticosteroids, my cophenolate -mofetil) within 28 days of screening. Topical steroid use is prohibited within 2 weeks of screening in VT and on scalp, eyebrows, and eyelids in AA• Intralesional steroid injection within 8 weeks of screening or within 5 half-lives, whichever is longer• Herbal medications, including traditional Chinese medicine formulations, with unknown properties or known beneficial effects for VT or alopecia• Untreated latent tuberculosis as indicated by IFNy release assay, without documentation of appropriate treatment (appropriate therapy as defined by the World Health Organization and / or the United States Centers for Disease Control and Prevention)• Estimated glomerular filtration rate < 30 mE / min / 1 ,73m2(using the Chronic Kidney Disease Epidemiology Collaboration formula; Levey, A.S. et al. (2009) Ann Intern Med. 150(9): 604-612)• Total bilirubin >1.5 upper limit of normal (ULN; >3 x ULN if known Gilbert’s disease)• Aspartate aminotransferase and alanine aminotransferase > 2.5 x ULN

[0235] Alopecia areata-specific exclusion criteria include:• Diffuse AA, other forms of alopecia, and other active inflammatory diseases of the scalp• Use of phototherapy, platelet-rich plasma injections, or non-steroid topical immunosuppressives during the trial and within 12 weeks or 5 half-lives prior to screening• Any history of disseminated / complicated herpes zoster• History of eczema herpeticum within 12 months prior to screening or a history of 2 or more episodes of eczema herpeticum in the past

[0236] Vitiligo-specific exclusion criteria include:• Subjects that have other types of VT (including but not limited to segmental VT). Mixed VT is permitted• Currently have active forms of other hypopigmentation (including but not limited to Vogt- Koyanagi-Harada disease, malignancy-induced hypopigmentation [melanoma and mycosis fungoides], post-inflammatory hypopigmentation, pityriasis alba [minor manifestation of atopic dermatitis], senile leukoderma [age-related depigmentation], chemical / drug -induced leukoderma, ataxia telangiectasia, tuberous sclerosis, melasma, and congenital hypopigmentation disorders75MOFO-360690948Attorney Docket No. 18654-2001540 including piebaldism, Waardenburg syndrome, hypomelanosis of Ito, incontinentia pigmenti, dyschromatosis symmetrica hereditaria, xeroderma pigmentosum, and nevus depigmentosus). Coexistence of halo nevus / nevi (also known as Sutton nevus / nevi) is permitted• Currently active forms of inflammatory skin disease(s) or evidence of skin conditions (including but not limited to morphea, discoid lupus, leprosy, syphilis, psoriasis, seborrheic dermatitis) at screening that in the opinion of the Investigator would interfere with evaluation of VT or response to treatment• Use of permanent depigmentation treatment for VT and / or other types of depigmentation disorders (e.g., monobenzene or phenol) at any time• Use of ultraviolet B phototherapy, psoralen ultraviolet A therapy, or other phototherapy within 4 weeks of screening• Any history of disseminated / complicated or relapsing herpes zoster• History of eczema herpeticum within 12 months prior to screening or a history of 2 or more episodes of eczema herpeticum in the past

[0237] Safety assessments including monitoring of AEs, clinical laboratory tests (blood), physical examinations, and vital signs. Toxicities are graded and documented according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).

[0238] For subjects with AA, clinical activity is evaluated using the SALT score (Olsen, E. et al. (1999) Jam Acad Dermatol. 40(2 Pt l):242-246). This system divides the scalp into quadrants which are scored for hair loss and combined to a sum score.

[0239] For subjects with VT, clinical activity is evaluated using the facial-VASI (F-VASI). The total- VASI (T-VASI) evaluating the whole body is also used as a supportive clinical activity measure. T-VASI was developed to quantify severity of disease over the whole body (Hamzavi, I. et al. (2004) Arch Dermatol. 140(6):677-683), and F-VASI represents the facial component of the score.

[0240] For LP, eligible subjects include biopsy-confirmed, moderate to severe, treatment-refractory LP eligible for systemic therapy, including all forms of LP (e.g., cutaneous, mucosal / oral, genital, esophageal, otic, nail) and also lichen planopilaris.Example 2: Pre-Clinical Study of Anti-CD94 AntibodyMaterials and MethodsAssessment of CD94 by flow cytometry in peripheral blood of healthy donors and autoimmune patients

[0241] CD94+CD8+ T cells as a percentage of live peripheral blood mononuclear cells (PBMCs) of 18 healthy donors (HD), 1 alopecia areata (AA), 14 rheumatoid arthritis (RA), and 2 vitiligo (VT) patients were assessed by flow cytometry. Briefly, PBMCs were resuspended in fragment crystallizable region (Fc) block (BioLegend, Cat#422302) at a ratio of 1: 100 and cell viability dye (eBioscience, Cat#65-0866-76MOFO-360690948Attorney Docket No. 18654-200154018) at a ratio of 1: 1000 in fluorescent activated cell sorting (FACS) buffer [lx phosphate buffered saline (VWR, Cat#45000-446) and 2% fetal bovine serum (VWR, Cat#10018-830)] and incubated on ice for 30 minutes protected from light. Cells were washed and incubated in an appropriate amount of cell surface antibody cocktail containing anti-human CD3 (BioLegend, Cat#:317324), CD4 (BioLegend, Cat#317426), CD8 (BioLegend, Cat#344756), CD56 (BD, Cat#566573), CD16 (BioLegend, Cat#302018), CD45RA (BioLegend, Cat#304114), CCR7 (BioLegend, Cat#353204), and CD94 (BD, Cat#559876) antibodies. Cells were incubated with antibody for 30 minutes on ice protected from light, followed by 1 wash step. The cells were acquired on the flow cytometer (CytoFLEX LX, ID# 80567067, Beckman Coulter). Cell populations were identified using appropriate markers.CD94 immunohistochemistry of lichen planus skin biopsies

[0242] Formalin-fixed paraffin-embedded (FFPE) skin biopsies from n=10 lichen planus (LP) patients and n=10 healthy donors (HD) were procured from Precision for Medicine and iSpecimen, respectively. Samples were analyzed by immunohistochemistry (IHC) for the expression of CD94 using a proprietary method developed and qualified at Mosaic Laboratories (Lake Forest, CA, USA). Digital images of the CD94-stained sections as well as hematoxylin and eosin (H&E)-stained sections were provided to a certified pathologist for interpretation. H-scoring was used to semi-quantify CD94 expression on the mononuclear cells.ResultsAssessment of CD94 by flow cytometry in peripheral blood of healthy donors and autoimmune patients

[0243] The percentage of CD94+CD8+ T cells was determined in PBMC samples of patients with autoimmune disease and healthy donors by flow cytometry. There was on average a 3.5-fold increase in the percentage of CD94+CD8+ T cells in the peripheral blood of autoimmune patients relative to those of healthy donor controls (FIG. 2).CD94 immunohistochemistry of lichen planus skin biopsies

[0244] The percentage of CD94 cells and CD94 expression levels by H-score in 10 LP and 10 HD skin biopsy samples were determined by IHC. There was on average a 3-fold increase in the abundance of CD94+ mononuclear cells and CD94 expression level in LP samples compared to HD samples (FIG. 3A and FIG. 3B). Example histological images of the skin biopsies show increased inflammation within the dermis of LP, as opposed to HD in which no inflammation was observed. CD94 staining was also apparent in the LP sample compared to the HD sample (FIG. 3C and FIG. 3D).

[0245] These data demonstrate that alopecia areata, vitiligo, rheumatoid arthritis, including Felty’s syndrome, and inclusion body myositis are strong candidates for treatment with anti-CD94 antibodies, such as DR-01.77MOFO-360690948Attorney Docket No. 18654-2001540

[0246] Although the present disclosure has been described in some detail by way of illustration and example for purposes of clarity of understanding, the descriptions and examples should not be construed as limiting the scope of the present disclosure. The disclosures of all patent and scientific literature cited herein are expressly incorporated in the entirety by reference.MOFO-360690948

Claims

1. Attorney Docket No. 18654-2001540CLAIMSWhat is claimed is:

1. A method of treating an autoimmune disease or disorder in an individual in need thereof, the method comprising administering to the individual one or more doses of an antibody that specifically binds to human CD94, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg; wherein the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3, and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6.

2. The method of claim 1, wherein the autoimmune disease or disorder is Felty’s syndrome, rheumatoid arthritis (RA), inclusion body myositis, alopecia areata (AA), vitiligo (VT), or lichen planus (LP).

3. The method of claim 2, wherein the AA is moderate to severe AA.

4. The method of claim 2 or claim 3, wherein, prior to administration of the antibody to the individual, the individual has a current episode of AA lasting from greater than 6 months to less than 10 years.

5. The method of any one of claims 2-4, wherein the individual does not have diffuse AA.

6. The method of claim 2, wherein the VT is non-segmental VT.

7. The method of claim 2, wherein the LP is cutaneous LP, mucosal LP, appendageal LP, or lichen planopilaris.

8. The method of claim 2, wherein the LP is selected from Oral Lichen Planus, Cutaneous Lichen Planus, Esophageal Lichen Planus, Genital Lichen Planus, Lichen Planopilaris, Nail Lichen Planus, Lichen Planus Pigmentosus, Hypertrophic Lichen Planus, Bullous Lichen Planus, and Inverse Lichen Planus.

9. The method of any one of claims 1-8, wherein administration of the antibody to the individual results in a reduction in one or more symptoms of the autoimmune disease or disorder in the individual.

10. The method of any one of claims 1-9, wherein administration of the antibody to the individual results in depletion of CD94+ cells in the individual.79MOFO-360690948Attorney Docket No. 18654-200154011. The method of claim 10, wherein administration of the antibody to the individual results in depletion of CD8+ CD94+ T cells in the individual.

12. The method of any one of claims 1-11, wherein the one or more doses of the antibody is / are administered to the individual as part of a pharmaceutical composition comprising the antibody and one or more pharmaceutically acceptable carriers.

13. The method of any one of claims 1-12, wherein the one or more doses of the antibody is / are administered intravenously to the individual.

14. The method of any one of claims 1-13, comprising administering to the individual two or more doses of 24mg, 80mg, 240mg, or 450mg of the antibody at an interval of 1 week or 7 days.

15. The method of any one of claims 1-14, comprising administering to the individual two or more doses of 24mg, 80mg, 240mg, or 450mg of the antibody at an interval of 2 weeks or 14 days.

16. The method of any one of claims 1-15, comprising administering to the individual two or more doses of 24mg, 80mg, 240mg, or 450mg of the antibody at an interval of 4 weeks or 28 days.

17. The method of any one of claims 1-16, wherein the antibody is administered to the individual on Day 1, Day 8, Day 15, and Week 4.

18. The method of claim 17, wherein, after Week 4, the antibody is administered to the individual once every 4 weeks.

19. The method of any one of claims 1-18, wherein at least one of the doses of the antibody is administered to the individual intravenously in a first portion of the dose on a first day and the remaining portion of the dose on the next day.

20. The method of claim 19, wherein the first dose of the antibody is administered to the individual intravenously in a first portion of the first dose on Day 1 and the remaining portion of the first dose on Day 2.

21. The method of claim 20, wherein the first dose of the antibody is administered to the individual intravenously in a first portion of lOmg on Day 1 and the remainder of the first dose on Day 2.

22. The method of claim 20 or claim 21, wherein the first portion of the first dose is administered to the individual intravenously over 4 hours on Day 1, and the remainder of the first dose is administered to the individual intravenously over 4 hours on Day 2.80MOFO-360690948Attorney Docket No. 18654-200154023. The method of any one of claims 1-22, wherein, after the first dose, the antibody is administered intravenously to the individual over 2-3 hours.

24. The method of claim 23, wherein the antibody is administered intravenously to the individual over 3 hours on Day 8 and Day 15, and over 2 hours on Week 4 and subsequent doses.

25. The method of any one of claims 1-13, wherein the antibody is administered to the individual at a dose of 24mg on Day 1, Day 8, Day 15, Week 4, Week 8, Week 12, Week 16, and Week 20.

26. The method of any one of claims 1-13, wherein the antibody is administered to the individual at a dose of lOmg on Day 1, 14mg on Day 2, 24mg on Day 8, 24mg on Day 15, 24mg on Week 4, 24mg on Week 8, 24mg on Week 12, 24mg on Week 16, and 24mg on Week 20.

27. The method of any one of claims 1-13, wherein the antibody is administered to the individual at a dose of 80mg on Day 1, Day 8, Day 15, Week 4, Week 8, Week 12, Week 16, and Week 20.

28. The method of any one of claims 1-13, wherein the antibody is administered to the individual at a dose of lOmg on Day 1, 70mg on Day 2, 80mg on Day 8, 80mg on Day 15, 80mg on Week 4, 80mg on Week 8, 80mg on Week 12, 80mg on Week 16, and 80mg on Week 20.

29. The method of any one of claims 1-13, wherein the antibody is administered to the individual at a dose of 240mg on Day 1, Day 8, Day 15, Week 4, Week 8, Week 12, Week 16, and Week 20.

30. The method of any one of claims 1-13, wherein the antibody is administered to the individual at a dose of lOmg on Day 1, 230mg on Day 2, 240mg on Day 8, 240mg on Day 15, 240mg on Week 4, 240mg on Week 8, 240mg on Week 12, 240mg on Week 16, and 240mg on Week 20.

31. The method of any one of claims 1-13, wherein the antibody is administered to the individual at a dose of 450mg on Day 1, Day 8, Day 15, Week 4, Week 8, Week 12, Week 16, and Week 20.

32. The method of any one of claims 1-13, wherein the antibody is administered to the individual at a dose of lOmg on Day 1, 440mg on Day 2, 450mg on Day 8, 450mg on Day 15, 450mg on Week 4, 450mg on Week 8, 450mg on Week 12, 450mg on Week 16, and 450mg on Week 20.

33. The method of any one of claims 1-32, further comprising administering a corticosteroid to the individual prior to one or more doses of the antibody.

34. The method of claim 33, wherein the corticosteroid is methylprednisolone.

35. The method of claim 34, wherein 80mg methylprednisolone is administered intravenously to the individual at least 60 minutes and no more than 3 hours prior to the first dose of the antibody.81MOFO-360690948Attorney Docket No. 18654-200154036. The method of claim 35, wherein the first dose of the antibody is administered to the individual intravenously in a first portion of the first dose on Day 1 and the remaining portion of the first dose on Day 2, and wherein 80mg methylprednisolone is administered intravenously to the individual at least 60 minutes and no more than 3 hours prior to the first portion of the first dose on Day 1 and at least 60 minutes and no more than 3 hours prior to the remaining portion of the first dose on Day 2.

37. The method of any one of claims 1-36, further comprising administering an anti -pyretic to the individual prior to one or more doses of the antibody.

38. The method of claim 37, wherein the anti-pyretic is acetaminophen.

39. The method of claim 38, wherein 650-1000mg acetaminophen is administered orally to the individual at least 30 minutes and no more than 3 hours prior to one or more doses of the antibody.

40. The method of any one of claims 1-39, further comprising administering an antihistamine to the individual prior to one or more doses of the antibody.

41. The method of claim 40, wherein the antihistamine is diphenhydramine, cetirizine, or loratadine.

42. The method of claim 41, wherein 50mg diphenhydramine is administered orally to the individual at least 30 minutes and no more than 3 hours prior to one or more doses of the antibody.

43. The method of any one of claims 1-42, wherein the VH domain of the antibody comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain of the antibody comprises the amino acid sequence of SEQ ID NO: 17.

44. The method of any one of claims 1-43, wherein the antibody is a human antibody.

45. The method of any one of claims 1-44, wherein the antibody is a full-length antibody that comprises an Fc region.

46. The method of claim 45, wherein the Fc region is a human IgGl Fc region.

47. The method of claim 45 or claim 46, wherein the antibody comprises a human Fc region that is non-fucosylated.

48. The method of any one of claims 1-43, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:65 and a light chain comprising the amino acid sequence of SEQ ID NO:66.

49. The method of any one of claims 1-48, wherein the antibody is a monoclonal, monospecific antibody.82MOFO-360690948Attorney Docket No. 18654-200154050. The method of any one of claims 1-43, wherein the antibody is dibotatug.

51. An antibody that specifically binds to human CD94 for use in a method of treating an autoimmune disease or disorder in an individual in need thereof, said method comprising administering the antibody to the individual one or more doses of the antibody, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg; wherein the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3; and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6; optionally wherein the VH domain of the antibody comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain of the antibody comprises the amino acid sequence of SEQ ID NO: 17; optionally wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:65 and a light chain comprising the amino acid sequence of SEQ ID NO:66; optionally wherein the antibody is dibotatug.

52. Use of an antibody that specifically binds to human CD94 in the manufacture of a medicament for treating an autoimmune disease or disorder in an individual in need thereof, wherein the medicament comprises one or more doses of 24mg, 80mg, 240mg, or 450mg of the antibody.

53. An article of manufacture, comprising a container comprising one or more doses of an antibody that specifically binds to human CD94, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg; wherein the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3, and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6; optionally wherein the VH domain of the antibody comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain of the antibody comprises the amino acid sequence of SEQ ID NO: 17; optionally wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:65 and a light chain comprising the amino acid sequence of SEQ ID NO:66; optionally wherein the antibody is dibotatug.

54. The article of manufacture of claim 53, wherein the container comprises one or more doses of 24mg of the antibody.83MOFO-360690948Attorney Docket No. 18654-200154055. The article of manufacture of claim 53, wherein the container comprises one or more doses of 80mg of the antibody.

56. The article of manufacture of claim 53, wherein the container comprises one or more doses of 240mg of the antibody.

57. The article of manufacture of claim 53, wherein the container comprises one or more doses of 450mg of the antibody.

58. The article of manufacture of any one of claims 53-57 for use in the treatment of an autoimmune disease or disorder, wherein the autoimmune disease or disorder is Felty’s syndrome, rheumatoid arthritis (RA), inclusion body myositis, alopecia areata (AA), vitiligo (VT), or lichen planus (LP).

59. The article of manufacture of any one of claims 53-58, wherein the antibody is dibotatug.

60. A kit, comprising:(a) one or more doses of an antibody that specifically binds to human CD94, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg, wherein the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3; and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR- L3 comprising the amino acid sequence of SEQ ID NO:6; and(b) a package insert with instructions for administering the antibody to an individual in need thereof at one or more doses selected from 24mg, 80mg, 240mg, and 450mg according to the method of any one of claims 1-50.

61. A method of treating an autoimmune disease or disorder in an individual in need thereof, the method comprising administering to the individual one or more doses of dibotatug, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg.

62. The method of claim 61, wherein the autoimmune disease or disorder is rheumatoid arthritis (RA), Felty’s syndrome, inclusion body myositis, alopecia areata (AA), vitiligo (VT), or lichen planus (LP).

63. An article of manufacture, comprising a container comprising one or more doses of dibotatug, wherein each of the one or more doses is the same dose selected from 24mg, 80mg, 240mg, and 450mg.84MOFO-360690948Attorney Docket No. 18654-200154064. The article of manufacture of claim 63, wherein the container comprises one dose of dibotatug, and wherein the dose is selected from 24mg, 80mg, 240mg, and 450mg.

65. A method of treating an autoimmune disease or disorder in an individual in need thereof, the method comprising administering to the individual one or more doses of an antibody that specifically binds to human CD94, wherein the autoimmune disease or disorder is alopecia areata (AA), vitiligo (VT), or lichen planus (LP).

66. The method of claim 65, wherein the individual is a human.

67. The method of claim 65 or claim 66, wherein the AA is moderate to severe AA.

68. The method of claim 65 or claim 66, wherein the VT is non-segmental VT.

69. The method of claim 65 or claim 66, wherein the LP is cutaneous LP, mucosal LP, appendagealLP, or lichen planopilaris.

70. The method of claim 65 or claim 66, wherein the LP is selected from Oral Lichen Planus, Cutaneous Lichen Planus, Esophageal Lichen Planus, Genital Lichen Planus, Lichen Planopilaris, Nail Lichen Planus, Lichen Planus Pigmentosus, Hypertrophic Lichen Planus, Bullous Lichen Planus, and Inverse Lichen Planus.

71. The method of any one of claims 65-70, wherein binding of the antibody to human CD94 does not block binding between human CD94 and human HLA-E.

72. The method of any one of claims 65-71, wherein the antibody binds human CD94 expressed on the surface of a cell, optionally a human natural killer (NK) cell or a human CD8+ CD94+ T cell.

73. The method of any one of claims 65-72, wherein the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3, and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6.

74. The method of claim 73, wherein the VH domain of the antibody comprises the amino acid sequence of SEQ ID NO: 16, and the VL domain of the antibody comprises the amino acid sequence of SEQ ID NO: 17.

75. The method of any one of claims 65-74, wherein the antibody is a human antibody.85MOFO-360690948Attorney Docket No. 18654-200154076. The method of any one of claims 65-75, wherein the antibody is a full-length antibody that comprises an Fc region.

77. The method of claim 76, wherein the Fc region is a human IgGl Fc region.

78. The method of claim 76 or claim 77, wherein the antibody comprises a human Fc region that is non-fucosylated.

79. The method of any one of claims 65-72, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:65 and a light chain comprising the amino acid sequence of SEQ ID NO:66.

80. The method of any one of claims 65-79, wherein the antibody is a monoclonal, monospecific antibody.

81. The method of any one of claims 65-72, wherein the antibody is dibotatug.86MOFO-360690948

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