PD-1 agonist antibody and method for treating autoimmune diseases using PD-1 agonist antibody

Abstract

The present disclosure relates to methods and uses of novel PD-1 agonist antibodies and anti-human PD-1 agonist antibodies for the treatment of autoinflammatory and / or autoimmune diseases. Dosage and administration regimens for the methods and uses of anti-human PD-1 agonist antibodies for the treatment of autoinflammatory and / or autoimmune diseases, such as RA, are also provided.

Description

[Technical Field]

[0001] (Sequence Listing) This application has been submitted with a Sequence Listing in ST.26 XML format. The Sequence Listing is provided as a file entitled "30388 WO.xml," created on August 4, 2023, and is 48.8 kilobytes in size. The Sequence Listing information in ST.26 XML format is incorporated herein by reference in its entirety.

[0002] FIELD OF THE INVENTION The present disclosure relates generally to methods of treating autoinflammatory and / or autoimmune diseases, such as rheumatoid arthritis (RA), with antibodies that bind to human programmed cell death protein 1, also known as human PD-1, and inhibit T cell activation through agonism of the PD-1 pathway. More particularly, the disclosure relates to methods of treating autoinflammatory and / or autoimmune diseases, such as RA, with the PD-1 agonist monoclonal antibody peresolimab. [Background technology]

[0003] PD-1 and its ligands, PD-L1 and PD-L2, are key components of the PD-1 pathway, which is involved in immune homeostasis. Deficiencies in the PD-1 pathway, which plays an important pathophysiological role, have been demonstrated in autoinflammatory and / or autoimmune diseases, such as psoriasis (Gulati et al., 2015), psoriatic arthritis (PsA) (see, e.g., Bommarito et al., 2017), vasculitis (see, e.g., Zhang et al., 2017), multiple sclerosis (MS) (see, e.g., Trabattoni et al., 2009), systemic lupus erythematosus (SLE) (see, e.g., Mozaffarian, N. et al., 2008), systemic sclerosis (SSc) (see, e.g., Fukasawa et al., 2017), type 1 diabetes mellitus (T1DM) (see, e.g., Guleria, I. et al., 2007), and RA (see, e.g., Canavan et al., 2021).

[0004] RA is an autoimmune disease characterized by chronic inflammation of synovial tissue, leading to the destruction of joint structures. In some individuals, the disease can damage a wide variety of body systems, including the skin, eyes, lungs, heart, and blood vessels. A hallmark of the disease is symmetric polyarthritis, characteristically involving the small joints of the hands and feet. Systemic inflammation is characterized by laboratory abnormalities, such as anemia, elevated erythrocyte sedimentation rate, fibrinogen, and C-reactive protein (CRP), as well as clinical symptoms of fatigue, weight loss, and muscle atrophy in affected joint areas. The presence of polyclonal, high-titer rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies is evidence of immune dysregulation. Increased expression of PD-1 on T cells has been shown to correlate with immune activation and disease activity in RA patients.

[0005] RA can adversely affect a patient's ability to perform daily activities and potentially reduce their health-related quality of life. The primary goals of current RA treatments are to alleviate the signs and symptoms of the disease, prevent structural damage to bone and cartilage, and improve physical function and social participation, thereby improving health-related quality of life. Various treatment options available for managing RA and other autoinflammatory and / or autoimmune diseases include glucocorticoids and disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs (csDMARDs), biological DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs). However, many patients with RA and other autoinflammatory and / or autoimmune diseases are poor responders, non-responders, or intolerant to such treatments, and in the case of RA, disease, including joint destruction, continues to progress despite various currently available treatments. In fact, it is believed that 20–40% of RA patients do not respond to current treatments (see, e.g., NCT05460832).

[0006] Although the PD-1 pathway has been reported to have an important pathophysiological role in autoinflammatory and / or autoimmune diseases, there has been intense interest in targeting this pathway for at least 15 years, and anti-PD-1 antibodies that are reported to be agonists have been generated (see, e.g., WO 2019 / 168745 and WO 2017 / 058859), the field has yet to provide a safe and effective method for treating any disease, including autoinflammatory and / or autoimmune diseases, using PD-1 agonist antibodies.

[0007] Thus, there remains a significant need for novel PD-1 agonist antibodies and / or improved therapeutic approaches, particularly in the form of PD-1 agonist antibody dosing regimens, that result in stimulation of physiological immunoinhibitory pathways to restore immunoregulation and safely provide superior and / or durable efficacy in patients with autoinflammatory and / or autoimmune diseases, including patients with moderate to severe active RA who have had an inadequate response to previous csDMARDs, bDMARDs and / or tsDMARDs. Summary of the Invention

[0008] Accordingly, in a first aspect of the present disclosure, there is provided a method of treating an autoinflammatory disease and / or an autoimmune disease, comprising administering to a patient in need of treatment an effective amount of a polypeptide that binds to the human PD-1 extracellular domain (ECD) with an affinity of about 1 pM to about 100 nM, as measured by surface plasmon resonance (SPR) at 25°C, and that binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) administering an antibody that binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, wherein binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist.

[0009] In a second aspect of the present disclosure, there is provided a method for treating an autoinflammatory disease and / or an autoimmune disease, the method comprising administering to a patient in need of treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises a heavy chain variable region (HCVR) and a light chain variable region (LCVR), the HCVR comprising heavy chain complementarity determining regions (HCDRs) HCDR1, HCDR2, and HCDR3, and the LCVR comprising light chain complementarity determining regions (LCDRs) LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO:10.

[0010] In a third aspect of the present disclosure, there is provided a method for treating an autoinflammatory disease and / or an autoimmune disease, the method comprising administering to a patient in need of treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises an HCVR and an LCVR, the HCVR comprising heavy chain complementarity-determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprising light chain complementarity-determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) The antibody binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, and the binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist.

[0011] In another aspect, an antibody is provided that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, and binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD; a) human IgG1 Fc region variants, including P247I and A339Q; b) a human IgG1 Fc region variant comprising S298A, E333A, and K334A; c) human IgG1 Fc region variants, including S239D and I332E; d) human IgG1 Fc region variants, including S239D, I332E, and A330L; e) human IgG1 Fc region variants, including G236A, S239D, and I332E; and f) human IgG1 Fc region variants comprising G236A, S239D, I332E, and A330L, wherein the antibody is a human PD-1 agonist.

[0012] In another aspect, the disclosure provides an antibody, wherein the antibody binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, and the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody a) human IgG1 Fc region variants, including P247I and A339Q; b) a human IgG1 Fc region variant comprising S298A, E333A, and K334A; c) human IgG1 Fc region variants, including S239D and I332E; d) human IgG1 Fc region variants, including S239D, I332E, and A330L; e) human IgG1 Fc region variants, including G236A, S239D, and I332E; and f) human IgG1 Fc region variants comprising G236A, S239D, I332E, and A330L, wherein the antibody is a human PD-1 agonist. [Brief explanation of the drawings]

[0013] [Figure 1] The primary efficacy outcome measure in a Phase 2(a) study of peresolimab in participants with moderately to severely active RA, DAS28-CRP CFB at week 12, showed significantly greater improvements in participants treated with intravenous (IV) Q4W 700 mg peresolimab (LSM=-2.09, CI=-2.46, -1.72, p<0.001) and 300 mg peresolimab (LSM=-1.88, CI=-2.37, -1.38, p=0.017) versus placebo (LSM=-0.99, CI=-1.51, -0.47). [Figure 2] Participants treated with 700 mg peresolimab (p<0.001) and 300 mg peresolimab (p<0.01) administered intravenously Q4W demonstrated significantly greater improvement versus placebo in CDAI at week 12 in a Phase 2(a) study of peresolimab in participants with moderately to severely active RA. [Figure 3]In a Phase 2(a) study of peresolimab in participants with moderately to severely active RA, patients treated with intravenous peresolimab 700 mg and 300 mg Q4W who achieved a CDAI at week 14 maintained a high level of CDAI response through week 24. *p<0.05, ***p<0.001 vs. placebo; multiplicity was not controlled and nominal p-values ​​are reported. aLSM change from baseline to week 12; observed mean change from baseline from weeks 14 to 24. [Figure 4] PD-1 mAb agonism correlates with PD-1 binding affinity, indicating that higher affinity mAbs are more effective in inhibiting T cell proliferation. More specifically, human CFSE-labeled PBMCs were incubated for 3 days in the presence of SEB and 30 μg of one of human IgG1 PD-1 mAbs A–D. Proliferation upon mAb treatment was quantified by assessing the number of CD4 T cells with reduced CFSE staining using flow cytometry. The half maximal inhibitory concentration (IC50) for each PD-1 affinity variant is shown. Data are representative of two independent experiments. [Figure 5] Figure 1 shows the effect of PD-1 mAb with a human IgG1 Fc variant on SEB-induced human PBMC proliferation. Human PBMC were stimulated in triplicate for 3 days in the presence of SEB and 30 μg / mL of F1-derived PD-1 mAb (A) or G2-derived PD-1 mAb (B) treatment. Results shown are the % T cell proliferation compared to untreated samples, mean + / - SEM of 6 donors for (A) and 8-10 donors for (B). DETAILED DESCRIPTION OF THE INVENTION

[0014] This disclosure describes novel PD-1 agonist antibodies and enhancers of PD-1 antibody-mediated agonism, and provides the first meaningful evidence of the clinical efficacy of PD-1 agonists in autoinflammatory and / or autoimmune diseases, and the first such results in rheumatism.

[0015] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the analogs, pharmaceutical compositions, and methods, the preferred methods and materials are described herein.

[0016] Furthermore, the reference to an element by the indefinite article "a" or "an" does not exclude the possibility that a plurality of elements is present, unless the context clearly requires that there is one and only one element. Thus, the indefinite article "a" or "an" normally means "one."

[0017] Specific abbreviations are defined as follows: ACR = American College of Rheumatology, ACR20 = 20% improvement on American College of Rheumatology criteria, ACR50 = 50% improvement on American College of Rheumatology criteria, ACR70 = 70% improvement on American College of Rheumatology criteria, AE = adverse event, CI = confidence interval, CFB = change from baseline, CDAI = Clinical Disease Activity Index, CRP = C-reactive protein, hsCRP = high-sensitivity C-reactive protein, DAS28 = Disease Activity Score modified to include 28 mobile joint counts, HAQ-DI = Health Assessment Questionnaire Disability Index, LSM = least squares means, LDA = low disease activity, PRO = patient-reported outcome, SAE = serious adverse event, SDAI = simplified Disease Activity Index, SF-36 = 36-item Short-Form Health Status Questionnaire, VAS = visual analog scale.

[0018] The term "about," when used to modify a numerically defined parameter, means that the parameter may vary by as much as 10% above and below the stated numerical value for that parameter. For example, a dose of about 1000 mg administered subcutaneously once every four weeks (SC Q4W) should be understood to mean that the dose may vary from 900 mg SC Q4W to 1100 mg SC Q4W.

[0019] As used herein, the phrase "active rheumatoid arthritis" or "active RA" is used to mean RA with obvious signs and symptoms (eg, swelling, difficulty bending, etc.).

[0020] As used herein, an "antibody" is an immunoglobulin molecule capable of specifically binding to a protein target, such as human PD-1, through at least one antigen recognition site located in the variable region of the immunoglobulin molecule. As used herein, the term "antibody" refers to an engineered, non-naturally occurring polypeptide complex comprising an intact antibody and any antigen-binding fragment thereof (i.e., the "antigen-binding portion" or "antibody-binding domain" of an antibody). An intact antibody structurally comprises four polypeptide chains: two heavy chains and two light chains interconnected by disulfide bonds. Each heavy chain is composed of an N-terminal heavy chain variable region (HCVR) and a heavy chain constant region. Each light chain is composed of an N-terminal light chain variable region (LCVR) and a light chain constant region. The HCVRs and LCVRs can be further subdivided into regions of high variability called complementarity-determining regions (CDRs), separated by more conserved regions called framework regions (FRs). Each HCVR and LCVR consists of three CDRs and four FRs, arranged from the amino terminus to the carboxy terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen.The assignment of amino acid residues to CDRs can be performed using the sequences of Kabat (Kabat et al., "Sequences of Proteins of Immunological Interest," National Institutes of Health, Bethesda, Md. (1991)), Chothia (Chothia et al., "Canonical structures for the hypervariable regions of immunoglobulins," Journal of Molecular Biology, 196, 901-917 (1987); Al-Lazikani et al., "Standard conformations for the canonical structures of immunoglobulins," Journal of Molecular Biology, 273, 927-948 (1997)), North (North et al., "A New Clustering of Antibody CDR Loop Conformations," Journal of Molecular Biology, 406, 228-256 (2011)), or IMGT (the international standard available at www.imgt.org). This may be done according to well-known schemes, including those described in the ImMunoGeneTics database; see Lefranc et al., Nucleic Acids Res. 1999;27:209-212). A combination of the IMGT and North CDR definitions was used for the exemplary human PD-1 agonist antibodies described herein. It is further understood that the term "antibody" encompasses any cellular post-translational modifications to antibodies, including, but not limited to, acylation and glycosylation.

[0021] The term "Fc region" as used herein defines the C-terminal region of an immunoglobulin heavy chain containing at least a portion of the constant region. This term includes native-sequence Fc regions and variant Fc regions. 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. Unless otherwise specified herein, the numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system (also referred to as 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.

[0022] As used herein, an "amino acid substitution" refers to the replacement of at least one existing amino acid residue in a given amino acid sequence with another, different, "replacement" amino acid residue.

[0023] As used herein, the term "variant Fc region" or "Fc region variant" refers to the amino acid sequence of an Fc region that differs from the sequence of a parent Fc region (or fragment thereof) by at least one amino acid substitution. Furthermore, substitutions are designated herein by the amino acid in the parent Fc, followed by the position number where the substitution occurs, followed by the amino acid that replaces the amino acid in the parent Fc region at the same position. For example, human IgG1 Fc region variant P247I indicates that the proline residue at position 247 of the parent human IgG1 Fc region has been replaced by an isoleucine residue.

[0024] As used herein, the term "disease-modifying antirheumatic drug (DMARD)" refers to a class of drugs used to slow disease progression in the treatment of autoinflammatory and / or autoimmune diseases. DMARDs include csDMARDs, bDMARDs, and tsDMARDs.

[0025] As used herein, the term "conventional synthetic antirheumatic drug (csDMARD)" refers to a class of synthetic drugs (not biologics) used in the treatment of autoinflammatory and / or autoimmune diseases. Exemplary csDMARDs include, but are not limited to, azathioprine, methotrexate, hydroxychloroquine, leflunomide, and sulfasalazine.

[0026] As used herein, the term "biological disease-modifying antirheumatic drug (bDMARD)" refers to drugs produced using biotechnology methods. There are two main categories: TNF inhibitors (including, but not limited to, adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab, and biosimilars of any of the foregoing) and non-TNF inhibitors (including, but not limited to, tocilizumab, sarilumab, abatacept, anakinra, rituximab, and biosimilars of any of the foregoing).

[0027] An "effective amount" of a therapeutic agent, e.g., a pharmaceutical formulation, refers to an amount effective, at the necessary dosage and for the necessary period of time, to achieve the desired therapeutic or prophylactic result. An "effective amount" of a therapeutic agent provided herein can be administered by any suitable means, including parenteral, subcutaneous, intraperitoneal, intrapulmonary, and intranasal. Parenteral infusions include intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration. In certain embodiments, the medication is given by injection, e.g., intravenous or subcutaneous injection. In yet other embodiments, the therapeutic agent is administered using a syringe (e.g., pre-filled or unfilled) or an auto-injector.

[0028] PD-1 polypeptide "extracellular domain" or "ECD" refers to a form of PD-1 polypeptide that is essentially free of transmembrane and cytoplasmic domains. Preferably, the PD-1 ECD has less than 1% of the transmembrane and cytoplasmic domains, and more preferably, the PD-1 ECD has less than 0.5% of such domains. Even more preferably, the human PD-1 ECD polypeptide is as set forth in SEQ ID NO: 14, the cynomolgus monkey PD-1 ECD polypeptide is as set forth in SEQ ID NO: 16, and the mouse PD-1 ECD is as set forth in SEQ ID NO: 18. PD-1 polypeptide ECDs may be prepared using methods well known in the art. Alternatively, human PD-1 polypeptide ECDs can be commercially purchased from various vendors, such as Sino Biological (Beijing, China; reference number 10377-H08) and R&D Systems (Minneapolis, MN, USA; cat. #8986-PD). Cynomolgus monkey PD-1 polypeptide ECD can be commercially purchased from R&D Systems (Minneapolis, MN, USA, cat. #8509-PD).

[0029] As used herein, a "human PD-1 agonist antibody" refers to an antibody that binds to human PD-1 and, when administered in vivo, results in at least one significantly reduced autoimmune activity, such as reduced anti-double-stranded DNA (ds-DNA) titers, inhibition of T cell activation, inhibition of T cell proliferation, reduced disease score, or reduced inflammatory cytokines.

[0030] The term "patient" or "subject" refers to any single subject for whom treatment is desired or who is participating in a clinical trial, epidemiological study, or used as a control. A "patient" or "subject" according to the present disclosure includes, but is not limited to, an individual who may have had an inadequate response to, or who may have failed, or who may be intolerant to, a currently available DMARD, csDMARD, bDMARD, or tsDMARD, or an individual who has not previously been treated with a bDMARD.

[0031] As used herein, the term "peresolimab" refers to a monoclonal antibody that binds to human PD-1 and comprises two light chains and two heavy chains, each of which comprises the amino acid sequence of SEQ ID NO: 2 and each of which comprises the amino acid sequence of SEQ ID NO: 1. Furthermore, the light chain variable region and heavy chain variable region of peresolimab comprise the amino acid sequence of SEQ ID NO: 4 and SEQ ID NO: 3, respectively. Furthermore, as used herein, the term "peresolimab" is known in the art as LY3462817 and as Antibody 1 in WO 2019 / 168745, and is described in the World Health Organization (2021) "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 126" WHO Drug Information 35(4), pages 1056-1057. Preparation of peresolimab is described in WO 2019 / 168745.

[0032] As used herein, the term "4D8" refers to a humanized rabbit monoclonal antibody that binds to human PD-1 and human PD-1 ECD. Monoclonal antibody 4D8 comprises two light chains and two heavy chains, each of which comprises the amino acid sequence of SEQ ID NO: 20 and each of which comprises the amino acid sequence of SEQ ID NO: 19. Furthermore, the light chain variable region and heavy chain variable region of mAb 4D8 comprise the amino acid sequences of SEQ ID NO: 4 and SEQ ID NO: 3, respectively. Compared to peresolimab, 4D8 mAb binds to a similar, but not identical, epitope on human PD-1 ECD, and when bound to human PD-1 ECD, 4D8 mAb, like peresolimab, does not block the binding of human PDL1 to human PD-1 ECD.

[0033] As used herein, the term "F1" refers to the antigen-binding domain of mAb 4D8. As described herein, the antigen-binding domain of PD-1 antibodies, such as peresolimab and mAb 4D8, and variants thereof, can be paired with various human Fc regions, including, but not limited to, IgG1, IgG4, or Fc variants thereof, for purposes of, for example, assessing the effect of different human Fc regions on PD-1 antibody-mediated agonism of the PD-1 pathway.

[0034] As used herein, the term "G1" refers to an antigen-binding domain closely related to that of peresolimab. As described herein, G1 and its variants can be paired with various human Fc regions, including but not limited to, IgG1, IgG4, or Fc variants thereof, for purposes of evaluating the effect of different human Fc regions on PD-1 antibody-mediated agonism of the PD-1 pathway.

[0035] As used herein, the term "G2" refers to an antigen-binding domain that has amino acid sequence identity to the antigen-binding domain of peresolimab. As described herein, G2 and its variants can be paired with various human Fc regions, including, but not limited to, IgG1, IgG4, or Fc variants thereof, for purposes of, for example, evaluating the effect of different human Fc regions on PD-1 antibody-mediated agonism of the PD-1 pathway.

[0036] As used herein, the term "F2" refers to an antigen-binding domain identical to F1, except that F2 has two serine-to-cysteine ​​amino acid substitutions in the HCVR of the antigen-binding domain. More specifically, the HCVR region of F2 has cysteine ​​residues at positions 36 and 51 rather than the serine residues at positions 36 and 51 in the HCVR of 4D8 set forth in SEQ ID NO: 21. As described herein, F2 and variants thereof can be paired with various human Fc regions, including, but not limited to, IgG1, IgG4, or Fc variants thereof, for the purpose of evaluating the effect of different human Fc regions on PD-1 antibody-mediated agonism of the PD-1 pathway, for example.

[0037] As used herein, the terms "F-series" and "G-series" refer to antibodies or antigen-binding fragments thereof that are humanized rabbit mAbs that bind to similar, but not identical, epitopes on the human PD-1 ECD and do not block PDL1 binding. The G-series also do not block PDL2 binding, whereas the F-series partially blocks PDL2.

[0038] As used herein, "pharmaceutically acceptable buffer" means any of the standard pharmaceutical buffers known to those of skill in the art.

[0039] As used herein, the term "targeted synthetic disease-modifying antirheumatic drug (tsDMARD)" refers to drugs that are taken orally and target specific molecular pathways, such as Janus kinase inhibitors, e.g., tofacitinib, baricitinib, and upadatinib.

[0040] As used herein, "treatment" or "treating" refers to any process that may slow, control, or halt the progression of the diseases disclosed herein, but does not necessarily indicate the complete disappearance of all disease symptoms. Treatment includes the administration of the antibodies described herein to treat a disease or condition in a patient, particularly a human.

[0041] As used herein, the term "inadequate response" or "failure" to a previous treatment refers to: (1) patients who have no meaningful clinical benefit (primary lack of efficacy); (2) patients who have a measurable and meaningful response but do not achieve a better response, e.g., a reduction in disease activity or remission; (3) patients who deteriorate after an initial good response (secondary loss of efficacy); and (4) patients who have a good response but discontinue due to side effects (also referred to as "intolerance"). Patients who show an inadequate response to TNF (TNF-IR) or intolerance to TNF are considered TNF failures. Patients who show an inadequate response to methotrexate (MTX-IR) or intolerance to MTX are considered MTX failures. Patients who show an inadequate response to DMARDs (DMARD-IR) or intolerance to DMARDs are considered DMARD failures. In some embodiments of the disclosed methods, regimens, uses, and pharmaceutical compositions, the patient is a TNF failure, an MTX failure, or a DMARD failure.

[0042] As used herein, "clinical disease activity measures" for autoimmune diseases include the American College of Rheumatology (ACR) 20, ACR50, ACR70, Disease Activity Score (DAS), Disease Activity Score for RA with C-reactive protein-28 (DAS28-CRP), Psoriasis Area and Severity Index (PASI) 50, PASI75, PASI90, PASI100, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Mayo Score Disease Activity Index (DAI), Geboes score (GS), Roberts Histopathology Index (RHI), Atopic Dermatitis Severity Index (ADI), and the Psoriasis Area and Severity Index (PASI). DSI), hypoglycemic events for type 1 diabetes, HbA1c, % time in range (blood glucose by CGM), total daily dose of insulin and / or measurements of C-peptide under standardized conditions (including but not limited to total 4-hour C-peptide area under the curve (AUC) mixed meal tolerance test (MMTT)), change from baseline in proteinuria and complete renal response for e.g., lupus nephritis, and the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI)).

[0043] As used herein, the term "Clinical Disease Activity Index (CDAI)" refers to a well-known measure of disease activity in subjects with RA. The CDAI is a composite score integrating the TJC28 (scored 0-28, with high scores indicating high disease activity), the SJC28 (scored 0-28, with high scores indicating high disease activity), the patient's global assessment of disease activity (scored on a 0-10 cm visual analog scale, with high scores indicating high disease activity), and the physician's global assessment of disease activity (scored on a 0-10 cm visual analog scale, with high scores indicating high disease activity). The CDAI is calculated by summing the values ​​of the four components. The CDAI score ranges from 0 to 76, with low scores indicating low disease activity. A negative change from baseline indicates an improvement in the condition. The CDAI can be easily assessed and calculated by those skilled in the art using the following formula: CDAI = SJC(28) + TJC(28) + PGA + EGA SJC(28): Number of swollen joints out of 28 (shoulders, elbows, wrists, MCP, PIP including thumb IP, knees), TJC(28): Number of tender joints out of 28 (shoulders, elbows, wrists, MCP, PIP including thumb IP, knees), PGA or PatGA: Patient global disease activity (patient's self-assessment of comprehensive RA disease activity on a scale of 1 to 10, with 10 being maximal activity), EGA: Rater global disease activity (rater's assessment of comprehensive RA disease activity on a scale of 1 to 10, with 10 being maximal activity).

[0044] [Table 1]

[0045] As used herein, the term "36-Item Short Form Health Questionnaire (SF-36)" refers to a well-known health-related survey that assesses participants' health status. It consists of 36 questions covering eight health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health, mental health, social functioning, and vitality. The eight domains are combined to form two component scores: mental (MCS) and physical (PCS). Each domain is scored by summing the individual items and converting the score to a scale of 0 to 100, with higher scores indicating better health.

[0046] As used herein, the term "Simplified Disease Activity Index (SDAI)" refers to a tool for measuring disease activity in RA that integrates measures of physical examination, acute phase response, patient self-assessment, and rater assessment. The SDAI is calculated by summing the scores of: 1) TJC28 (0-28); 2) SJC28 (0-28); 3) acute phase response using C-reactive protein (0.1-10.0 mg / dL); 4) patient global assessment of disease activity using a visual analog scale (VAS) (0-10 cm); and 5) physician global assessment of disease activity using a visual analog analog scale (VAS) (0-10 cm). The total score scale ranges from 0 (remission) to 86 (high disease activity).

[0047] In one aspect of the present disclosure, there is provided a method of treating an autoinflammatory disease and / or an autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of a polypeptide that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, and binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) administering an antibody that binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, wherein binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist.

[0048] In a second aspect of the present disclosure, there is provided a method for treating an autoinflammatory disease and / or an autoimmune disease, the method comprising administering to a patient in need of treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises an HCVR and an LCVR, the HCVR comprising heavy chain complementarity-determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprising light chain complementarity-determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO:10.

[0049] In a third aspect of the present disclosure, there is provided a method for treating an autoinflammatory disease and / or an autoimmune disease, the method comprising administering to a patient in need of treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises an HCVR and an LCVR, the HCVR comprising heavy chain complementarity-determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprising light chain complementarity-determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10; The antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) The antibody binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, and the binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist.

[0050] In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO:3 and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO:4.

[0051] In some embodiments, the antibody comprises an immunoglobulin constant region.

[0052] In some embodiments, the immunoglobulin constant region is IgG1.

[0053] In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0054] In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO:1 and each light chain comprising the amino acid sequence of SEQ ID NO:2.

[0055] In some embodiments, the antibody is peresolimab.

[0056] In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, lupus nephritis (LN), cutaneous lupus erythematosus (CLE), giant cell arteritis (GCA), vasculitis, ulcerative colitis (UC), Crohn's disease (CD), Sjögren's syndrome (SjS), or T1DM.

[0057] In another embodiment, the antibody is administered subcutaneously to the patient at about 75 mg to about 1200 mg once a week (Q1W).

[0058] In another embodiment, the antibody is administered subcutaneously to a patient at about 100 mg to about 1150 mg Q1W.

[0059] In another embodiment, the antibody is administered subcutaneously to a patient at about 150 mg to about 1100 mg Q1W.

[0060] In another embodiment, the antibody is administered subcutaneously to a patient at about 200 mg to about 1050 mg Q1W.

[0061] In another embodiment, the antibody is administered subcutaneously to a patient at about 250 mg to about 1000 mg Q1W.

[0062] In another embodiment, the antibody is administered subcutaneously to a patient at about 300 mg to about 950 mg Q1W.

[0063] In another embodiment, the antibody is administered subcutaneously to a patient at about 350 mg to about 900 mg Q1W.

[0064] In another embodiment, the antibody is administered subcutaneously to a patient at about 400 mg to about 850 mg Q1W.

[0065] In another embodiment, the antibody is administered subcutaneously to a patient at about 450 mg to about 800 mg Q1W.

[0066] In another embodiment, the antibody is administered subcutaneously to a patient at about 500 mg to about 750 mg Q1W.

[0067] In another embodiment, the antibody is administered subcutaneously to a patient at about 550 mg to about 700 mg Q1W.

[0068] In another embodiment, the antibody is administered subcutaneously to a patient at about 600 mg to about 700 mg Q1W.

[0069] In another embodiment, the antibody is administered subcutaneously to a patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q1W.

[0070] In another embodiment, the antibody is administered subcutaneously to the patient at about 75 mg to about 1200 mg once every four weeks (Q4W).

[0071] In another embodiment, the antibody is administered subcutaneously to a patient at about 100 mg to about 1150 mg Q4W.

[0072] In another embodiment, the antibody is administered subcutaneously to a patient at about 150 mg to about 1100 mg Q4W.

[0073] In another embodiment, the antibody is administered subcutaneously to a patient at about 200 mg to about 1050 mg Q4W.

[0074] In another embodiment, the antibody is administered subcutaneously to a patient at about 250 mg to about 1000 mg Q4W.

[0075] In another embodiment, the antibody is administered subcutaneously to a patient at about 300 mg to about 950 mg Q4W.

[0076] In another embodiment, the antibody is administered subcutaneously to a patient at about 350 mg to about 900 mg Q4W.

[0077] In another embodiment, the antibody is administered subcutaneously to a patient at about 400 mg to about 850 mg Q4W.

[0078] In another embodiment, the antibody is administered subcutaneously to a patient at about 450 mg to about 800 mg Q4W.

[0079] In another embodiment, the antibody is administered subcutaneously to a patient at about 500 mg to about 750 mg Q4W.

[0080] In another embodiment, the antibody is administered subcutaneously to a patient at about 550 mg to about 700 mg Q4W.

[0081] In another embodiment, the antibody is administered subcutaneously to a patient at about 600 mg to about 700 mg Q4W.

[0082] In another embodiment, the antibody is administered subcutaneously to a patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W.

[0083] In other embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to standard treatments for autoinflammatory and / or autoimmune diseases.

[0084] In other embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: steroids; csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0085] In other embodiments, the patient has not previously been treated with a bDMARD.

[0086] In other embodiments, the patient has had an inadequate response to or failed two or less of the following: 1) no more than two bDMARDs, 2) no more than two tsDMARDs, or 3) any combination of inadequate response or failure to a bDMARD and a tsDMARD. For clarity, in such embodiments, the patient may have had, for example, an inadequate response to one bDMARD and one tsDMARD, or a failure to one bDMARD and an inadequate response to one tsDMARD, but the patient would not have had two inadequate responses to two different bDMARDs and a failure to one tsDMARD.

[0087] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 75 mg to about 1200 mg Q4W.

[0088] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 100 mg to about 1150 mg Q4W.

[0089] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 150 mg to about 1100 mg Q4W.

[0090] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 200 mg to about 1050 mg Q4W.

[0091] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 250 mg to about 1000 mg Q4W.

[0092] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 300 mg to about 950 mg Q4W.

[0093] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 350 mg to about 900 mg Q4W.

[0094] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 400 mg to about 850 mg Q4W.

[0095] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 450 mg to about 800 mg Q4W.

[0096] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 500 mg to about 750 mg Q4W.

[0097] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 550 mg to about 700 mg Q4W.

[0098] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 600 mg to about 700 mg Q4W.

[0099] In other embodiments, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W.

[0100] In another embodiment, if the patient achieves a clinical response with a Clinical Disease Activity Index (CDAI) < 10, the antibody is administered subcutaneously to the patient once every 12 weeks (Q12W), or the antibody continues to be administered subcutaneously to the patient Q4W.

[0101] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 75 mg to about 1200 mg Q12W.

[0102] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 100 mg to about 1150 mg Q12W.

[0103] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 150 mg to about 1100 mg Q12W.

[0104] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 200 mg to about 1050 mg Q12W.

[0105] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 250 mg to about 1000 mg Q12W.

[0106] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 300 mg to about 950 mg Q12W.

[0107] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 350 mg to about 900 mg Q12W.

[0108] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 400 mg to about 850 mg Q12W.

[0109] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 450 mg to about 800 mg Q12W.

[0110] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 500 mg to about 750 mg Q12W.

[0111] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 550 mg to about 700 mg Q12W.

[0112] In another embodiment, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 600 mg to about 700 mg Q12W.

[0113] In other embodiments, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W.

[0114] In some embodiments, the antibody is peresolimab.

[0115] In some embodiments, patients administered peresolimab at the doses, frequencies, and routes disclosed above experience a statistically significant increase (compared to patients administered a placebo at the same doses, frequencies, and routes) in measures of disease activity such as: The proportion of patients achieving ACR20 The proportion of patients achieving ACR50 The proportion of patients achieving ACR70 The proportion of patients achieving remission for LDA or DAS28-CRP or DAS28-hsCRP, DAS28-ESR, SDAI, and CDAI, Change from baseline in mean DAS28-CRP or DAS28-hsCRP, SDAI, and CDAI, and / or change from baseline in ACR core set scores for 68 tender joint count, 66 swollen joint count, and Physician's Global Assessment of Disease Activity (VAS) at Weeks 12, 24, 48, and / or 60.

[0116] In some embodiments, patients administered peresolimab at the doses, frequencies, and routes disclosed above experience a statistically significant increase (compared to patients administered a placebo at the same doses, frequencies, and routes) in measures of patient-reported outcomes such as: Change from baseline in patient-reported ACR core set scores, such as patient global assessment of disease activity (VAS), patient arthritis pain assessment (VAS), and / or patient assessment of physical function using the HAQ-DI; Change from baseline in duration and severity of morning joint stiffness, and / or Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT F) score at weeks 12, 24, 48, and / or 60; Change from baseline in SF-36 domains, SF-36 Physical Component Summary, and / or SF-36 Mental Component Summary at Weeks 12, 24, 48, and / or 60.

[0117] Also provided herein is an antibody that binds to human PD-1 for use in treating an autoinflammatory disease and / or an autoimmune disease, the treatment comprising administering to a patient in need thereof about 75 mg to about 1200 mg of an antibody, wherein the antibody comprises an HCVR and an LCVR, the HCVR comprising HCDR1, HCDR2, and HCDR3, and the LCVR comprising LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO:10.

[0118] In some embodiments, the antibody for use in treating an autoinflammatory and / or autoimmune disease comprises an HCVR comprising the amino acid sequence of SEQ ID NO:3 and an LCVR comprising the amino acid sequence of SEQ ID NO:4.

[0119] In some embodiments, the antibody for use in treating an autoinflammatory and / or autoimmune disease comprises an immunoglobulin constant region.

[0120] In some aspects, the antibody for use in treating an autoinflammatory and / or autoimmune disease comprises an immunoglobulin constant region, and the immunoglobulin constant region is an IgG1.

[0121] In some embodiments, the antibody for use in treating an autoinflammatory and / or autoimmune disease comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2.

[0122] In some embodiments, antibodies for use in treating autoinflammatory and / or autoimmune diseases comprise two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2.

[0123] In some aspects, the antibody for use in treating an autoinflammatory and / or autoimmune disease is peresolimab.

[0124] In some embodiments, the antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 75 mg to about 1200 mg Q1W.

[0125] In some embodiments, an antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 100 mg to about 1150 mg Q1W.

[0126] In some embodiments, an antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 150 mg to about 1100 mg Q1W.

[0127] In some embodiments, an antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 200 mg to about 1050 mg Q1W.

[0128] In some embodiments, an antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 250 mg to about 1000 mg Q1W.

[0129] In some embodiments, an antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 300 mg to about 950 mg Q1W.

[0130] In some embodiments, an antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 350 mg to about 900 mg Q1W.

[0131] In some embodiments, an antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 400 mg to about 850 mg Q1W.

[0132] In some embodiments, an antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 450 mg to about 800 mg Q1W.

[0133] In some embodiments, an antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 500 mg to about 750 mg Q1W.

[0134] In some embodiments, an antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 550 mg to about 700 mg Q1W.

[0135] In some embodiments, an antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 600 mg to about 700 mg Q1W.

[0136] In some embodiments, an antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q1W.

[0137] In some embodiments, an antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W.

[0138] In some embodiments, an antibody for use in treating an autoinflammatory and / or autoimmune disease is administered subcutaneously to a patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W.

[0139] In some embodiments, the antibody is for use in the treatment of an autoinflammatory and / or autoimmune disease, wherein the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM.

[0140] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, and the patient has had an inadequate response to, failed, or was intolerant to one or more csDMARDs, bDMARDs, tsDMARDs, TNF inhibitors, and / or non-TNF inhibitors.

[0141] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, and the patient has not previously received treatment with a bDMARD.

[0142] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 75 mg to about 1200 mg Q4W.

[0143] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 100 mg to about 1150 mg Q4W.

[0144] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 150 mg to about 1100 mg Q4W.

[0145] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 200 mg to about 1050 mg Q4W.

[0146] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 250 mg to about 1000 mg Q4W.

[0147] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 300 mg to about 950 mg Q4W.

[0148] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 350 mg to about 900 mg Q4W.

[0149] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 400 mg to about 850 mg Q4W.

[0150] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 450 mg to about 800 mg Q4W.

[0151] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 500 mg to about 750 mg Q4W.

[0152] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 550 mg to about 700 mg Q4W.

[0153] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 600 mg to about 700 mg Q4W.

[0154] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W.

[0155] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, and if the patient achieves a clinical response with a CDAI≦10, the antibody is administered subcutaneously to the patient Q12W, or the antibody continues to be administered subcutaneously to the patient Q4W.

[0156] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 75 mg to about 1200 mg Q12W.

[0157] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 100 mg to about 1150 mg Q12W.

[0158] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 150 mg to about 1100 mg Q12W.

[0159] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 200 mg to about 1050 mg Q12W.

[0160] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 250 mg to about 1000 mg Q12W.

[0161] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 300 mg to about 950 mg Q12W.

[0162] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 350 mg to about 900 mg Q12W.

[0163] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 400 mg to about 850 mg Q12W.

[0164] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 450 mg to about 800 mg Q12W.

[0165] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 500 mg to about 750 mg Q12W.

[0166] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 550 mg to about 700 mg Q12W.

[0167] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 600 mg to about 700 mg Q12W.

[0168] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, the patient is an adult patient with moderate to severe active RA, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W.

[0169] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, wherein patients administered the PD-1 agonist antibody at the doses, frequencies, and routes disclosed herein result in a statistically significant increase (compared to patients administered a placebo at the same doses, frequencies, and routes) in a measure of disease activity such as: The proportion of patients achieving ACR20 The proportion of patients achieving ACR50 The proportion of patients achieving ACR70 The proportion of patients achieving remission for LDA or DAS28-CRP or DAS28-hsCRP, DAS28-ESR, SDAI, and CDAI, Change from baseline in mean DAS28-CRP or DAS28-hsCRP, SDAI, and CDAI, and / or change from baseline in ACR core set scores for 68 tender joint count, 66 swollen joint count, and Physician's Global Assessment of Disease Activity (VAS) at Weeks 12, 24, 48, and / or 60.

[0170] In some embodiments, the antibody is for use in treating an autoinflammatory and / or autoimmune disease, wherein patients administered peresolimab at the doses, frequencies, and routes disclosed above provide a statistically significant increase (compared to patients administered a placebo at the same doses, frequencies, and routes) in a patient-reported outcome measure such as: Change from baseline in patient-reported ACR core set scores, such as patient global assessment of disease activity (VAS), patient arthritis pain assessment (VAS), and / or patient assessment of physical function using the HAQ-DI; Change from baseline in duration and severity of morning joint stiffness, and / or Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT F) score at weeks 12, 24, 48, and / or 60; Change from baseline in SF-36 domains, SF-36 Physical Component Summary, and / or SF-36 Mental Component Summary at Weeks 12, 24, 48, and / or 60.

[0171] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, wherein binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0172] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, wherein binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0173] In another aspect of the present disclosure, there is provided a method for treating an autoinflammatory disease and / or an autoimmune disease, the method comprising administering to a patient in need of treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises an HCVR and an LCVR, the HCVR comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and binding of the antibody to the ECD does not block human PD-L1 binding to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block human PD-L1 or human PD-L2 binding to the ECD. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0174] In another aspect of the present disclosure, there is provided a method for treating an autoinflammatory disease and / or an autoimmune disease, the method comprising administering to a patient in need of treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises an HCVR and an LCVR, the HCVR comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and binding of the antibody to the ECD does not block human PD-L1 binding to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block human PD-L1 or human PD-L2 binding to the ECD. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0175] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6.0 pM to about 1 μM against FcγRI; (ii) about 20 nM to about 10 μM for FcγRIIA_131H, (iii) about 4 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0176] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6.0 pM to about 1 μM against FcγRI; (ii) about 20 nM to about 10 μM for FcγRIIA_131H, (iii) about 4 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0177] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 nM against FcγRI; (ii) about 30 nM to about 10 μM for FcγRIIA_131H, (iii) about 5 nM to about 5 μM against FcγRIIA_131R, (iv) about 20 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0178] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 nM against FcγRI; (ii) about 30 nM to about 10 μM for FcγRIIA_131H, (iii) about 5 nM to about 5 μM against FcγRIIA_131R, (iv) about 20 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg once every 12 weeks Q12W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0179] In another aspect, the disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, comprising administering to a patient in need of treatment an effective amount of a PD-1 antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, and binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 1 μM for FcγRIIA_131H, (iii) about 5 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) administering an antibody that binds to FcγRIIIA_158F with an affinity of about 10 nM to about 1 μM, wherein binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0180] In another aspect, the disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, comprising administering to a patient in need of treatment an effective amount of a PD-1 antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, and binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 1 μM for FcγRIIA_131H, (iii) about 5 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) administering an antibody that binds to FcγRIIIA_158F with an affinity of about 10 nM to about 1 μM, wherein binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0181] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 250 nM for FcγRIIA_131H, (iii) about 50 nM to about 250 nM against FcγRIIA_131R, (iv) about 20 nM to about 250 nM against FcγRIIb, (v) about 10 nM to about 250 nM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 250 nM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0182] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 250 nM for FcγRIIA_131H, (iii) about 50 nM to about 250 nM against FcγRIIA_131R, (iv) about 20 nM to about 250 nM against FcγRIIb, (v) about 10 nM to about 250 nM μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 250 nM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0183] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 50 pM to about 100 pM against FcγRI; (ii) about 250 nM to about 1 μM for FcγRIIA_131H, (iii) about 50 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 500 nM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0184] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 50 pM to about 100 pM against FcγRI; (ii) about 250 nM to about 1 μM for FcγRIIA_131H, (iii) about 50 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 500 nM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0185] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 100 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 1.5 μM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of about 500 nM, and binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0186] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 100 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 1.5 μM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of about 500 nM, and binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0187] In another aspect, the disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises an HCVR and an LCVR, the HCVR comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO:10.

[0188] In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0189] In another aspect, the disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises an HCVR and an LCVR, the HCVR comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO:10.

[0190] In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0191] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0192] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0193] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6.0 pM to about 1 μM against FcγRI; (ii) about 20 nM to about 10 μM for FcγRIIA_131H, (iii) about 4 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0194] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6.0 pM to about 1 μM against FcγRI; (ii) about 20 nM to about 10 μM for FcγRIIA_131H, (iii) about 4 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0195] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 nM against FcγRI; (ii) about 30 nM to about 10 μM for FcγRIIA_131H, (iii) about 5 nM to about 5 μM against FcγRIIA_131R, (iv) about 20 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0196] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 nM against FcγRI; (ii) about 30 nM to about 10 μM for FcγRIIA_131H, (iii) about 5 nM to about 5 μM against FcγRIIA_131R, (iv) about 20 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0197] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 1 μM for FcγRIIA_131H, (iii) about 5 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA 158F with an affinity of about 10 nM to about 1 μM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0198] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 1 μM for FcγRIIA_131H, (iii) about 5 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 1 μM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0199] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6 pM to about 100 pM against FcγRI; (ii) about 50 nMpM to about 250 nM for FcγRIIA_131H, (iii) about 50 nM to about 250 nM against FcγRIIA_131R, (iv) about 20 nM to about 250 nM against FcγRIIb, (v) about 10 nM to about 250 nM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 250 nM, and the binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the binding of the antibody to the ECD does not block the binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0200] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6 pM to about 100 pM against FcγRI; (ii) about 50 nMpM to about 250 nM for FcγRIIA_131H, (iii) about 50 nM to about 250 nM against FcγRIIA_131R, (iv) about 20 nM to about 250 nM against FcγRIIb, (v) about 10 nM to about 250 nM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 250 nM, and the binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the binding of the antibody to the ECD does not block the binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0201] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 50 pM to about 100 pM against FcγRI; (ii) about 250 nM to about 1 μM for FcγRIIA_131H, (iii) about 50 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 500 nM, and the binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the binding of the antibody to the ECD does not block the binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0202] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 50 pM to about 100 pM against FcγRI; (ii) about 250 nM to about 1 μM for FcγRIIA_131H, (iii) about 50 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 500 nM, and the binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the binding of the antibody to the ECD does not block the binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0203] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 100 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 1.5 μM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of approximately 500 nM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0204] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 100 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 1.5 μM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of approximately 500 nM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0205] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 55 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 340 nM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of approximately 1.7 μM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0206] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 55 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 340 nM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of approximately 1.7 μM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q12W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0207] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, wherein binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0208] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, wherein binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0209] In another aspect of the present disclosure, there is provided a method for treating an autoinflammatory disease and / or an autoimmune disease, the method comprising administering to a patient in need of treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises an HCVR and an LCVR, the HCVR comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and binding of the antibody to the ECD does not block human PD-L1 binding to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block human PD-L1 or human PD-L2 binding to the ECD. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0210] In another aspect of the present disclosure, there is provided a method for treating an autoinflammatory disease and / or an autoimmune disease, the method comprising administering to a patient in need of treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises an HCVR and an LCVR, the HCVR comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and binding of the antibody to the ECD does not block human PD-L1 binding to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block human PD-L1 or human PD-L2 binding to the ECD. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0211] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6.0 pM to about 1 μM against FcγRI; (ii) about 20 nM to about 10 μM for FcγRIIA_131H, (iii) about 4 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0212] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6.0 pM to about 1 μM against FcγRI; (ii) about 20 nM to about 10 μM for FcγRIIA_131H, (iii) about 4 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0213] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 nM against FcγRI; (ii) about 30 nM to about 10 μM for FcγRIIA_131H, (iii) about 5 nM to about 5 μM against FcγRIIA_131R, (iv) about 20 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0214] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 nM against FcγRI; (ii) about 30 nM to about 10 μM for FcγRIIA_131H, (iii) about 5 nM to about 5 μM against FcγRIIA_131R, (iv) about 20 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0215] In another aspect, the disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, comprising administering to a patient in need of treatment an effective amount of a PD-1 antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, and binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 1 μM for FcγRIIA_131H, (iii) about 5 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) administering an antibody that binds to FcγRIIIA_158F with an affinity of about 10 nM to about 1 μM, wherein binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0216] In another aspect, the disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, comprising administering to a patient in need of treatment an effective amount of a PD-1 antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, and binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 1 μM for FcγRIIA_131H, (iii) about 5 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) administering an antibody that binds to FcγRIIIA_158F with an affinity of about 10 nM to about 1 μM, wherein binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0217] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 250 nM for FcγRIIA_131H, (iii) about 50 nM to about 250 nM against FcγRIIA_131R, (iv) about 20 nM to about 250 nM against FcγRIIb, (v) about 10 nM to about 250 nM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 250 nM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0218] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 250 nM for FcγRIIA_131H, (iii) about 50 nM to about 250 nM against FcγRIIA_131R, (iv) about 20 nM to about 250 nM against FcγRIIb, (v) about 10 nM to about 250 nM μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 250 nM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0219] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 50 pM to about 100 pM against FcγRI; (ii) about 250 nM to about 1 μM for FcγRIIA_131H, (iii) about 50 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 500 nM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0220] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 50 pM to about 100 pM against FcγRI; (ii) about 250 nM to about 1 μM for FcγRIIA_131H, (iii) about 50 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 500 nM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0221] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 100 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 1.5 μM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of about 500 nM, and binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0222] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 100 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 1.5 μM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of about 500 nM, and binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0223] In another aspect, the disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises an HCVR and an LCVR, the HCVR comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO:10.

[0224] In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0225] In another aspect, the disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises an HCVR and an LCVR, the HCVR comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0226] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0227] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0228] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6.0 pM to about 1 μM against FcγRI; (ii) about 20 nM to about 10 μM for FcγRIIA_131H, (iii) about 4 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0229] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6.0 pM to about 1 μM against FcγRI; (ii) about 20 nM to about 10 μM for FcγRIIA_131H, (iii) about 4 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0230] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 nM against FcγRI; (ii) about 30 nM to about 10 μM for FcγRIIA_131H, (iii) about 5 nM to about 5 μM against FcγRIIA_131R, (iv) about 20 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0231] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 nM against FcγRI; (ii) about 30 nM to about 10 μM for FcγRIIA_131H, (iii) about 5 nM to about 5 μM against FcγRIIA_131R, (iv) about 20 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0232] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 1 μM for FcγRIIA_131H, (iii) about 5 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA 158F with an affinity of about 10 nM to about 1 μM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0233] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 1 μM for FcγRIIA_131H, (iii) about 5 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 1 μM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0234] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6 pM to about 100 pM against FcγRI; (ii) about 50 nMpM to about 250 nM for FcγRIIA_131H, (iii) about 50 nM to about 250 nM against FcγRIIA_131R, (iv) about 20 nM to about 250 nM against FcγRIIb, (v) about 10 nM to about 250 nM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 250 nM, and the binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the binding of the antibody to the ECD does not block the binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0235] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6 pM to about 100 pM against FcγRI; (ii) about 50 nMpM to about 250 nM for FcγRIIA_131H, (iii) about 50 nM to about 250 nM against FcγRIIA_131R, (iv) about 20 nM to about 250 nM against FcγRIIb, (v) about 10 nM to about 250 nM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 250 nM, and the binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the binding of the antibody to the ECD does not block the binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0236] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 50 pM to about 100 pM against FcγRI; (ii) about 250 nM to about 1 μM for FcγRIIA_131H, (iii) about 50 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 500 nM, and the binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the binding of the antibody to the ECD does not block the binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0237] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 50 pM to about 100 pM against FcγRI; (ii) about 250 nM to about 1 μM for FcγRIIA_131H, (iii) about 50 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 500 nM, and the binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the binding of the antibody to the ECD does not block the binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0238] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 100 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 1.5 μM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of approximately 500 nM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0239] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 100 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 1.5 μM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of approximately 500 nM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0240] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 55 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 340 nM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of approximately 1.7 μM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q6W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0241] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 55 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 340 nM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of approximately 1.7 μM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q8W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0242] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, wherein binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0243] In another aspect of the present disclosure, there is provided a method for treating an autoinflammatory disease and / or an autoimmune disease, the method comprising administering to a patient in need of treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises an HCVR and an LCVR, the HCVR comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and binding of the antibody to the ECD does not block human PD-L1 binding to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block human PD-L1 or human PD-L2 binding to the ECD. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0244] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6.0 pM to about 1 μM against FcγRI; (ii) about 20 nM to about 10 μM for FcγRIIA_131H, (iii) about 4 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0245] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 nM against FcγRI; (ii) about 30 nM to about 10 μM for FcγRIIA_131H, (iii) about 5 nM to about 5 μM against FcγRIIA_131R, (iv) about 20 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0246] In another aspect, the disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, comprising administering to a patient in need of treatment an effective amount of a PD-1 antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, and binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 1 μM for FcγRIIA_131H, (iii) about 5 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) administering an antibody that binds to FcγRIIIA_158F with an affinity of about 10 nM to about 1 μM, wherein binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0247] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 250 nM for FcγRIIA_131H, (iii) about 50 nM to about 250 nM against FcγRIIA_131R, (iv) about 20 nM to about 250 nM against FcγRIIb, (v) about 10 nM to about 250 nM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 250 nM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0248] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 50 pM to about 100 pM against FcγRI; (ii) about 250 nM to about 1 μM for FcγRIIA_131H, (iii) about 50 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 500 nM, binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0249] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 100 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 1.5 μM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of about 500 nM, and binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the antibody does not bind to C1q as measured by SPR at 25°C. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0250] In another aspect, the disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises an HCVR and an LCVR, the HCVR comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody is not peresolimab. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0251] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM against FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H, (iii) about 1 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0252] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6.0 pM to about 1 μM against FcγRI; (ii) about 20 nM to about 10 μM for FcγRIIA_131H, (iii) about 4 nM to about 10 μM against FcγRIIA_131R, (iv) about 10 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0253] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 nM against FcγRI; (ii) about 30 nM to about 10 μM for FcγRIIA_131H, (iii) about 5 nM to about 5 μM against FcγRIIA_131R, (iv) about 20 nM to about 10 μM against FcγRIIb, (v) about 100 pM to about 10 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM, binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0254] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 7.5 pM to about 100 pM against FcγRI; (ii) about 50 nM to about 1 μM for FcγRIIA_131H, (iii) about 5 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA 158F with an affinity of about 10 nM to about 1 μM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0255] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 6 pM to about 100 pM against FcγRI; (ii) about 50 nMpM to about 250 nM for FcγRIIA_131H, (iii) about 50 nM to about 250 nM against FcγRIIA_131R, (iv) about 20 nM to about 250 nM against FcγRIIb, (v) about 10 nM to about 250 nM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 250 nM, and the binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the binding of the antibody to the ECD does not block the binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0256] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 50 pM to about 100 pM against FcγRI; (ii) about 250 nM to about 1 μM for FcγRIIA_131H, (iii) about 50 nM to about 1 μM against FcγRIIA_131R, (iv) about 20 nM to about 1 μM against FcγRIIb, (v) about 10 nM to about 1 μM against FcγRIIIA_158V, (vi) binds to FcγRIIIA_158F with an affinity of about 50 nM to about 500 nM, and the binding of the antibody to the ECD does not block the binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, the binding of the antibody to the ECD does not block the binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient has had an inadequate response to, failed, or was intolerant to one or more of the following medications: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0257] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 100 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 1.5 μM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of approximately 500 nM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q10W. In some embodiments, the patient is one who has had an inadequate response to, failed, or was intolerant to one or more of the following drugs: csDMARDs, bDMARDs, tsDMARDs, one or more TNF inhibitors, or One or more non-TNF inhibitors.

[0258] In another aspect, the present disclosure provides a method of treating an autoinflammatory and / or autoimmune disease, the method comprising administering to a patient in need of treatment an effective amount of an antibody that binds to human PD-1 ECD with an affinity of about 1 pM to about 100 nM as measured by SPR at 25°C, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions LCDR1, LCDR2, and LCDR3; HCDR1 comprises the amino acid sequence of SEQ ID NO: 5, HCDR2 comprises the amino acid sequence of SEQ ID NO: 6, HCDR3 comprises the amino acid sequence of SEQ ID NO: 7, LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; LCDR3 comprises the amino acid sequence of SEQ ID NO: 10, and the antibody selectively binds to at least one, at least two, at least three, or at least four of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) approximately 55 pM for FcγRI; (ii) approximately 900 pM for FcγRIIA_131H; (iii) approximately 1.5 μM for FcγRIIA_131R; (iv) approximately 5.2 μM against FcγRIIb; (v) approximately 340 nM against FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of approximately 1.7 μM, and binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist. In some embodiments, binding of the antibody to the ECD does not block binding of human PD-L1 or human PD-L2 to the ECD. In some embodiments, the antibody does not bind C1q as measured by SPR at 25°C. In some embodiments, the HCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 3, and the LCVR of the antibody comprises the amino acid sequence of SEQ ID NO: 4. In some embodiments, the antibody comprises an immunoglobulin constant region. In some embodiments, the immunoglobulin constant region is IgG1. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO: 2. In some embodiments, the antibody is not peresolimab. In some embodiments, the autoinflammatory and / or autoimmune disease is RA, SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM, and the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 80...

Claims

1. 1. A method of treating an autoinflammatory and / or autoimmune disease, comprising administering to a patient in need of said treatment an effective amount of an antibody that binds to the extracellular domain (ECD) of human programmed cell death protein 1 (human PD-1) with an affinity of about 1 pM to about 100 nM as measured by surface plasmon resonance (SPR) at 25°C, wherein the antibody binds to at least three of FcγRI, FcγRIIA_131H, FcγRIIA_131R, FcγRIIb, FcγRIIIA_158F, and FcγRIIIA_158V, respectively, as measured by SPR at 25°C. (i) about 1 pM to about 1 μM for FcγRI; (ii) about 10 nM to about 10 μM for FcγRIIA_131H; (iii) about 1 nM to about 10 μM for FcγRIIA_131R; (iv) about 10 nM to about 10 μM for FcγRIIb; (v) about 100 pM to about 10 μM for FcγRIIIA_158V; (vi) binds to FcγRIIIA_158F with an affinity of about 10 nM to about 10 μM; The method, wherein binding of the antibody to the ECD does not block binding of human PD-L1 to the ECD, and the antibody is a human PD-1 agonist.

2. 1. A method for treating an autoinflammatory or autoimmune disease, comprising administering to a patient in need of said treatment about 75 mg to about 1200 mg of an antibody that binds to human PD-1, wherein the antibody comprises a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein the HCVR comprises heavy chain complementarity determining regions (HCDRs) HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions (LCDRs) LCDR1, LCDR2, and LCDR3; the HCDR1 comprises the amino acid sequence of SEQ ID NO: 5; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 6; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 7; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; The method, wherein the LCDR3 comprises the amino acid sequence of SEQ ID NO:

10.

3. 3. The method of claim 2, wherein the HCVR comprises the amino acid sequence of SEQ ID NO:3 and the LCVR comprises the amino acid sequence of SEQ ID NO:

4.

4. The method of any one of claims 1 to 3, wherein the antibody comprises a human immunoglobulin constant region that is human IgG1.

5. The method of claim 4, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:

2.

6. 6. The method of claim 5, wherein the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO:

2.

7. 8. The method of claim 7, wherein the antibody is peresolimab.

8. 8. The method of any one of claims 1 to 7, wherein the disease is rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), lupus nephritis (LN), cutaneous lupus erythematosus (CLE), giant cell arteritis (GCA), vasculitis, ulcerative colitis (UC), Crohn's disease (CD), or type 1 diabetes mellitus (T1DM).

9. The patient: a. conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), b. biological disease-modifying antirheumatic drugs (bDMARDs); c. Targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs); d. a tumor necrosis factor (TNF) inhibitor, or e. The method of any one of claims 1 to 8, which has had an inadequate response to, failed to respond to, or is intolerant to, a non-TNF inhibitor.

10. The method of any one of claims 1 to 9, wherein the patient has not previously received treatment with a bDMARD.

11. The method of any one of claims 1 to 10, wherein the patient is an adult patient with moderate to severe active RA.

12. 12. The method of any one of claims 1-11, wherein the antibody is administered subcutaneously to the patient at about 100 mg to about 1150 mg Q1W.

13. 12. The method of any one of claims 1-11, wherein the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q1W.

14. 12. The method of any one of claims 1-11, wherein the antibody is administered to the patient subcutaneously at about 75 mg to about 1200 mg once every four weeks (Q4W), once every eight weeks (Q8W), or once every twelve weeks (Q12W).

15. 12. The method of any one of claims 1-11, wherein the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q4W, Q8W, or Q12W.

16. 1. An antibody that binds to human PD-1 for use in treating an autoinflammatory or autoimmune disease, said treatment comprising administering about 75 mg to about 1200 mg of the antibody to a patient in need thereof, wherein the antibody comprises an HCVR and an LCVR, wherein the HCVR comprises an HCDR1, an HCDR2, and an HCDR3, and wherein the LCVR comprises an LCDR1, an LCDR2, and an LCDR3; the HCDR1 comprises the amino acid sequence of SEQ ID NO: 5; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 6; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 7; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 8; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 9; An antibody, wherein the LCDR3 comprises the amino acid sequence of SEQ ID NO:

10.

17. The antibody for use according to claim 16, wherein the HCVR comprises the amino acid sequence of SEQ ID NO: 3 and the LCVR comprises the amino acid sequence of SEQ ID NO:

4.

18. 18. The antibody for use according to claim 16 or 17, wherein the antibody comprises a human IgG1 Fc region.

19. 19. The antibody for use according to claim 18, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO:

2.

20. 20. The antibody for use according to claim 19, wherein the antibody comprises two heavy chains and two light chains, each heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and each light chain comprising the amino acid sequence of SEQ ID NO:

2.

21. 21. The antibody for use according to claim 20, wherein the antibody is peresolimab.

22. The antibody for use according to any one of claims 16 to 20, wherein the antibody is administered subcutaneously to the patient Q1W, Q4W, Q8W, or Q12W.

23. 23. The antibody for use of claim 22, wherein the antibody is administered subcutaneously to the patient at about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about 1100 mg, about 1150 mg, or about 1200 mg Q1W, Q1W, Q4W, Q8W, or Q12W.

24. 24. The antibody for use according to claim 23, wherein the disease is SLE, LN, CLE, GCA, vasculitis, UC, CD, SjS, or T1DM.

25. 24. The antibody for use according to claim 23, wherein the disease is RA.

26. The patient a. csDMARD, b. bDMARD, c. tsDMARD, d. TNF inhibitors, or e. The antibody for use according to claim 25, which has had an inadequate response to, failed to respond to, or is intolerant to a non-TNF inhibitor.

27. 26. The antibody for use of claim 25, wherein the patient has not previously received treatment with a bDMARD.

28. The antibody for use according to any one of claims 25 to 27, wherein the patient is an adult patient with moderate to severe active RA.

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