Dosing of Anti-il-11rα antibodies in the treatment of idiopathic pulmonary fibrosis

Abstract

Provided are methods of treating idiopathic pulmonary fibrosis (IPF) comprising administering an antibody that binds to human interleukin-11 receptor subunit α (IL-11Rα) and related compositions.

Description

DOSING OF ANTI-IL-1 IRa ANTIBODIES IN THE TREATMENT OF IDIOPATHIC PULMONARY FIBROSISCROSS REFERENCE TO RELATED APPLCATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 657,748, filed on June 7, 2024, the content of which is incorporated by reference herein in its entirety.REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0002] The contents of the electronic sequence listing(LASS 01 l_01WO_SeqList_ST26.xml; Size: 93,646 bytes; and Date of Creation: June 2, 2025) are herein incorporated by reference in its entirety.BACKGROUND

[0003] Interleukin- 11 (IL-11) is a member of the IL-6 family, and plays a prominent role in chronic inflammation, autoimmunity, cancer, and other diseases. It also plays a critical role in the initiation and maintenance of fibro-inflammation in disease settings. Thus, IL-11 signaling inhibitors represent a promising therapeutic approach for treating a variety of diseases, including inflammatory diseases, autoimmune diseases, chronic fibrotic diseases, and cancers.

[0004] Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by scarring of lung tissue. Scarring of the lung tissue thickens and stiffens the tissue, leading to difficulties breathing and generally results in compromised lung function over time. Treatments for IPF such as Pirfenidone and Nintedanib generally aim to slow the progression of fibrosis and to relieve symptoms. However, the efficacy of the current treatments available for IPF varies widely between patients, and because IPF is a progressive disease, additional treatments are generally needed as the disease advances. Thus, there is a need in the art for additional and improved therapeutic approaches to treating IPF. Provided herein are compositions and methods that address this need.SUMMARY

[0005] The present disclosure relates to methods of treating idiopathic pulmonary fibrosis(IPF) by administering an antibody that binds to human interleukin-11 receptor subunit a (IL-1 IRa). Aspects of the disclosure provide dosing parameters for treating IPF in a human subject using an IL-1 IRa antibody of the disclosure.

[0006] In one aspect provided herein is a method of treating idiopathic pulmonary fibrosis (IPF) in a human subject in need thereof, comprising administering to the subject one or more dose(s) of about 300 mg to about 1200 mg per dose of an antibody which binds to human interleukin-11 receptor subunit a (IL-1 IRa). In some embodiments, the IL-1 IRa antibody comprises a heavy chain complementarity determining region (HCDR) 1, HCDR2, and HCDR3, and a light chain complementarity determining region (LCDR) 1, LCDR2, and LCDR3 selected form table 1. In some embodiments, the IL-1 IRa antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL) selected from table 2 or a sequence with at least 70% thereto. In some embodiments, the antibody comprises a heavy chain (HC) and a light chain (LC) selected from table 3 or a sequence with at least 70% identity thereto.

[0007] In some embodiments, the IL- 1 IRa antibody is a full-length antibody or an antibody fragment.

[0008] In some embodiments, the IL-1 IRa antibody comprises an Fc domain. In some embodiments, the Fc domain is selected form the group consisting of human IgGl, IgG2, IgG3, and IgG4 heavy chain sequence. In some embodiments, the Fc domain comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3. In some embodiments, the Fc domain comprises one or more amino acid substitutions. In some embodiments, the one or more amino acid substitutions comprises a S228P substitution, wherein the position number of the amino acid residue is of the EU numbering scheme. In some embodiments, the one or more amino acid substitutions extend the IL- 1 IRa antibody’s half-life. In some embodiments, the one or more amino acid substitutions are selected from the group consisting of M252Y, S254T, and T256E substitutions, wherein the position numbers of the amino acid residues are of the EU numbering scheme. In some embodiments, the one or more amino acid substitutions are selected from the group consisting of M428L and N434S substitutions, wherein the position numbers of the amino acid residues are of the EU numbering scheme. In some embodiments, the one or more amino acid substitutions are selected from the group consisting of L234A, L235A, and P329S substitutions, wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0009] In some embodiments, the dose is administered daily, weekly, about every two weeks, about every three weeks, about every four weeks, every month, or every two months. In some embodiments, the dose is administered intravenously, subcutaneously, intramuscularly,topically, orally, transdermally, intraperitoneally, intraorbitally, intrathecally, intraventricularly, intranasally, transmucosally, through implantation, through inhalation, or through an on-body device or infuser. In some embodiments, the dose is administered intravenously. In some embodiments, the dose is administered subcutaneously. In some embodiments, the dose is achieved by at least 2 to about 5 administrations. In some embodiments, the dose is administered at a volume of about 1 mL, about 2 mL, about 3 mL or about 4 mL. In some embodiments, the dose is administered at a volume of about 1 mL to about 25 mL. In some embodiments, a dose of about 1200 mg is administered intravenously to the subject at a volume of about 60 mL about every four weeks.

[0010] In some embodiments, the dissociation constant (KD) of the IL-1 IRa antibody to human IL-1 IRa is less than about 50 pM. In some embodiments, the IL-1 IRa antibody does not bind to mouse IL-1 IRa or rat IL-1 IRa. In some embodiments, the IL-1 IRa antibody inhibits IL-11 induced phosphorylation of STAT3. In some embodiments, the IL-1 IRa antibody inhibits IL-11 induced phosphorylation of ERK. In some embodiments, the IL- 1 IRa antibody inhibits procollagen release.

[0011] In some embodiments, an additional IPF therapy is administered during a course of treatment with the IL- 1 IRa antibody. In some embodiments, the additional IPF therapy is administered concurrently with the administration of the IL- 1 IRa antibody. In some embodiments, the additional IPF therapy is administered after the administration of the IL- 1 IRa antibody. In some embodiments, the additional IPF therapy is administered prior to the administration of the IL- 1 IRa antibody. In some embodiments, the additional IPF therapy is selected from the group consisting of anti-fibrotic, Pirfenidone, Nintedanib, PDE4 inhibitor (e.g., Nerandomilast (BI 1015550)), an Integrin inhibitor (e.g., Bexotegrast (PLN-74809)), and a hedgehog inhibitor (e.g., ENV-101 (taladegib)). In some embodiments, the at least one additional IPF therapy is administered intravenously, subcutaneously, intramuscularly, topically, orally, transdermally, intraperitoneally, intraorbitally, intrathecally, intraventricularly, intranasally, transmucosally, through implantation, through inhalation, or through an on-body device or infuser.

[0012] In another aspect provided herein is a bispecific antibody comprising: a first antigen binding arm that specifically binds to IL- 1 IRa, comprising a heavy chain complementarity determining region (HCDR) 1, HCDR2, and HCDR3, and a light chain complementarity determining region (LCDR) 1, LCDR2, and LCDR3 selected from table 1 and a second antigen binding arm that specifically binds to an IPF associated antigen.

[0013] In some embodiments, the first antigen binding arm comprises a heavy chain variable region (VH) and a light chain variable region (VL) selected from table 2 or a sequence with at least 70% thereto. In some embodiments, the IPF associated antigen is selected from the group consisting of a receptor tyrosine kinase (RTK) such as vascular endothelial growth factor (VEGF), fibroblast growth factor receptor (FGFR), and Platelet-derived growth factor receptor (PDGFR), PDE4, integrin, hedgehog, and connective tissue growth factor (CTGF). In some embodiments, the second antigen binding arm comprises a VH and a VL sequence derived from pamrevlumab.

[0014] In another aspect provided herein is an antibody-drug conjugate (ADC) comprising an antibody that specifically binds to IL- 1 IRa, wherein the antibody comprising a heavy chain complementarity determining region (HCDR) 1, HCDR2, and HCDR3, and a light chain complementarity determining region (LCDR) 1, LCDR2, and LCDR3 selected from table 1, a linker; and an IPF therapeutic drug. In some embodiments, the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL) selected from table 2 or a sequence with at least 70% identity thereto. In some embodiments, the IPF therapeutic drug is selected from the group consisting of an anti-fibrotic, Pirfenidone, Nintedanib, a PDE4 inhibitor, such as Nerandomilast (BI 1015550), a PI3K / mT0R inhibitor (e.g., Omipalisib), an Integrin inhibitor (e.g., PLN-74809), and a hedgehog inhibitor (e.g., ENV-101). In some embodiments, the linker is a cleavable linker.BRIEF DESCRIPTION OF THE FIGURES

[0015] FIG. 1 shows a summary chart of mAb5 binding, potency, and lung antifibrotic activity data.

[0016] FIG. 2 shows mAb5 induced reduction of collagen expression by IPF patient fibroblasts that were stimulated in culture with TGFp.

[0017] FIG. 3 shows a mAb5 induced reduction of fibrosis in human IPF lung tissue. Data from n=18 replicates. 3 slices per region from 2 different regions for each of 3 donors. 0.3 pg / mL = 2 nM; 3 pg / mL = 20 nM, 30 pg / mL = 200 nM. * p<0.05 compared to control using One-Way ANOVA with Dunnett’s post-test.

[0018] FIG. 4 shows a dose-dependent reduction in lung hydroxyproline in a 21 -day bleomycin-induced lung fibrosis mouse model by an exemplary IL-1 IRa antibody of the disclosure.

[0019] FIG. 5 shows pharmacokinetic (PK) modeling to estimate dose selection based on in vitro PCLS efficacy studies in IPF diseased tissue.

[0020] FIG. 6 shows a schematic of the mAh 5 human PK and safety study.

[0021] FIG. 7 shows mAb5 serum concentrations at the indicated doses for the single ascending dose (SAD) (panel A) and multiple ascending dose (MAD) (panel B) studies.

[0022] FIG. 8 shows a hyper IL- 11 -induced pSTAT3 activity in monocytes at each sampling timepoint by treatment regimen in subjects the MAD study.

[0023] FIG. 9 shows a hyper IL- 11 -induced pSTAT3 activity in monocytes at each sampling timepoint by treatment regimen in subjects the SAD study.

[0024] FIG. 10 shows the relationship between hyper IL-11 induced pSTAT3 activity in monocytes and mAb5 serum concentrations (pooled data from the SAD and MAD studies).

[0025] FIG. 11 shows a summary chart of the healthy volunteer mAb5 SAD / MAD safety data.

[0026] FIG. 12 shows a mAb5 induced reduction of the fibrotic markers, collagen I, fibronection and TEMP I in human IPF precision cut lung slices (PCLS).

[0027] FIG. 13 shows the effects of mAb5 on collagen production by hydroxyproline in a humanized mouse model of IPF involving adoptive transfer of mixed IPF lung cells into immunodeficient mice.

[0028] FIGS. 14A-14G shows subcutaneous dosing ranges translated from PK simulations. FIG. 14A shows a table comparing SC dosing regimens at different IV dose equivalents. FIG. 14B shows a table outlining acceptable SC dosing limits. FIG. 14C-14E show PK simulation summary tables comparing SC doses to 300 mg IV doses. FIG. 14F shows alternative SC dosing regimens across different dosing intervals and bioavailability assumptions. FIG. 14G shows a PK simulation summary table comparing SC doses to 600 mg IV a dose.DETAILED DESCRIPTIONDefinitions

[0029] Where elements are presented in a list format (e.g., in a Markush group), it should be understood that each possible subgroup of the elements is also disclosed, and that any one or more elements can be removed from the list or group.

[0030] It should be understood that, unless clearly indicated, in any method described or disclosed herein that includes more than one act, the order of the acts is not necessarily limited to the order in which the acts of the method are recited, but the disclosure encompasses exemplary embodiments in which the order of the acts is so limited.

[0031] The terms used throughout the specification are defined as follows unless otherwise limited in specific instances. As used in the specification and the claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. All technical and scientific terms, acronyms, and abbreviates used in the specification and claims have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure pertains, unless defined or stated otherwise. All numerical ranges are inclusive of the values defining the range as well as all integer values in between, unless indicated or defined otherwise.

[0032] The term antibody as used herein throughout is used in the broadest sense and includes a monoclonal antibody, polyclonal antibody, human antibody, humanized antibody, non-human antibody, chimeric antibody, a monovalent antibody, full-length antibody, and an antibody fragment.

[0033] In some embodiments, the IL- 1 IRa antibodies provided herein are antibody fragments, retaining IL- 1 IRa antigen binding specificity. In some embodiments, the antibody fragments are antigen -binding fragments (Fab), variable fragments (Fv) containing heavy chain variable region (VH) and light chain variable region (VL) sequences, single chain variable fragments (scFv) containing VH and VL sequences linked together in one chain, single chain antibody fragments (scAb) or other antibody variable region fragments, such as Fab’, F(ab’)2, dsFv diabody, and Fd polypeptide fragments.

[0034] The term full-length antibody refers to an antibody having a structure substantially similar to a native antibody structure comprising a tetrameric polypeptide, wherein the tetrameric polypeptide comprises two heavy chain polypeptides consisting of an N-terminal to a C-terminal direction of a heavy chain variable domain (VH), constant heavy chain domain 1 (CHI), hinge region (HR), and a fragment crystallizable (Fc) region comprising a constant heavy chain domain 2 (CH2) and a constant heavy chain domain 3 (CH3), abbreviated as VH-CH1-HR-CH2-CH3; and two light chain polypeptides consisting of an N- terminal to a C-terminal direction of a light chain variable domain (VL) and a constant light chain domain (CL), abbreviated VL-CL. The light chain polypeptide may be either a K (kappa) or (lambda) classification.

[0035] In exemplary embodiments, the IL- 1 IRa antibodies provided herein are monoclonal antibodies. In exemplary embodiments, the IL- 1 IRa antibodies provided herein are human antibodies. In exemplary embodiments, the IL- 1 IRa antibodies provided herein aremonoclonal human antibodies. In other exemplary embodiments, the IL-1 IRa antibodies provided herein are humanized antibodies.

[0036] The term “epitope” includes any determinant, preferably a polypeptide determinant, capable of specific binding to an immunoglobulin or T-cell receptor. An epitope includes a region of an antigen that is bound by an antibody. In certain embodiments, epitope determinants include chemically active surface groupings of molecules such as amino acids, sugar side chains, phosphoryl or sulfonyl, and may in certain embodiments have specific three-dimensional structural characteristics, and / or specific charge characteristics. Epitopes can be contiguous or non-contiguous in relation to the primary structure of the antigen, for example, an IL- 1 IRa polypeptide.

[0037] An “epitope” includes that portion of an antigen or other macromolecule capable of forming a binding interaction that interacts with the variable region binding pocket of a binding protein. Such binding interaction can be manifested as an intermolecular contact with one or more amino acid residues of a CDR or other amino acid in the antibody variable region. Antigen binding can involve a CDR3 or a CDR3 pair. An epitope can be a linear peptide sequence (i.e., “continuous”) or can be composed of noncontiguous amino acid sequences (i.e., “conformational” or “discontinuous”). A binding protein can recognize one or more amino acid sequences; therefore, an epitope can define more than one distinct amino acid sequence. Epitopes recognized by binding protein can be determined by peptide mapping and sequence analysis techniques well known to one of skill in the art.

[0038] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.I. IL-1 IRa Antibodies

[0039] Provided herein are antibodies that bind to IL- 1 IRa, and methods of treating IPF using such antibodies. The antibodies may be useful for treating IPF by blocking IL-11 mediated signaling.

[0040] The antibodies that bind to IL-1 IRa may be interchangeably referred to herein as IL- 1 IRa antibodies, anti-IL-1 IRa antibodies, IL-1 IRa-directed antibodies and the like.

[0041] In some embodiments, the antibody binds human IL-1 IRa. In some embodiments, the antibody binds to a fibronectin type-III domain of human IL-1 IRa. In some embodiments,the antibody antagonizes the binding and / or signaling activity between IL- 1 IRa and IL-11. In some embodiments, the IL- 1 IRa antibody does not bind mouse IL- 1 IRa. In some embodiments, the IL-1 IRa antibody does not bind rat IL-1 IRa. In some embodiments, the IL-1 IRa antibody does not bind mouse or rat IL-1 IRa.

[0042] In some embodiments, the IL-1 IRa antibodies of the disclosure contain an Fc domain. In some embodiments, the Fc domain (interchangeably referred to as a Fc sequence, Fc region, or simply Fc) of the IL-1 IRa antibodies is a human Fc domain. In some embodiments, the Fc domain of the IL-1 IRa antibodies is human IgGl, human IgG2, human IgG3, or human IgG4.

[0043] In some embodiments, the Fc domain of an IL- 1 IRa antibody of the disclosure comprises one or more Fc amino acid substitutions. In some embodiments, the Fc substitutions increase the half-life of the IL-1 IRa antibody. In some embodiments, the Fc substitutions include M252Y, S254T, and / or T256E wherein the position numbers of the amino acid residues are of the EU numbering scheme. In some embodiments, the Fc substitutions include M428L and / or N434S wherein the position numbers of the amino acid residues are of the EU numbering scheme. In some embodiments, the Fc substitutions include L234A, L235A, and / or P329S wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0044] In some embodiments, the Fc domain of the IL- 1 IRa antibodies of the disclosure is a human IgGl Fc sequence. An exemplary, but non-limiting, sequence of heavy chain constant regions of human IgGl encompassing Fc domains of interest are provided as SEQ ID NO: 1.ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 1)

[0045] In some embodiments, the Fc domain of an IL- 1 IRa antibody of the disclosure is from a human IgGl constant heavy chain (e.g. SEQ ID NO: 1) containing one or more Fc amino acid substitutions. In some embodiments, the Fc substitutions increase the half-life of the IL-1 IRa antibody. In some embodiments, the Fc substitutions include M252Y, S254T, and / or T256E wherein the position numbers of the amino acid residues are of the EU numbering scheme. In some embodiments, the Fc substitutions include M428L and / or N434S wherein the position numbers of the amino acid residues are of the EU numbering scheme. Insome embodiments, the Fc substitutions include L234A, L235A, and / or P329S wherein the position numbers of the amino acid residues are of the EU numbering scheme. In exemplary embodiments, the Fc substitutions include L234A, L235A, P329S, M252Y, S254T, and T256E.

[0046] The EU numbering scheme is one of many available antibody numbering schemes based on the residue numbers assigned to a canonical antibody sequence. Accordingly, a skilled artisan would understand that reference to a particular residue using the EU numbering scheme may or may not be exactly the residue in one of the IL- 1 IRa antibodies of the disclosure. For example, if an IL-1 IRa antibody of the disclosure comprises a M428L substitution in the Fc, wherein the position number of the amino acid residue is of the EU numbering scheme, the residue may not be the actual residue 428 in that particular IL-1 IRa antibody. It may be actual residue number 427, or 428, or 429, or others. Accordingly, a skilled artisan will understand how to correspond the recited residue using the EU numbering scheme, to the actual residue in an IL-1 IRa antibody of the disclosure. The EU numbering system for antibodies is known in the art and is described, for example, at imgt.org / IMGT S ci entifi cChart / Numb ering / Hu IGHGnb er . html .

[0047] In some embodiments, the Fc domain of the IL- 1 IRa antibodies of the disclosure is a human IgG4 Fc sequence. An exemplary, but non-limiting, sequence of heavy chain constant region of human IgG4 encompassing Fc domain of interest is provided as SEQ ID NO: 2. SEQ ID NO: 2 provides the canonical human IgG4 heavy chain constant region sequence. SEQ ID NO: 3 provides the canonical human IgG4 heavy chain constant region sequence with an S228P substitution wherein the position numbers of the amino acid residues are of the EU numbering scheme.ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVD HKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKT KPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO:2)ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVD HKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKT KPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO:3)

[0048] In some embodiments, the Fc domain of an IL- 1 IRa antibody of the disclosure is from a human IgG4 constant heavy chain (e.g. SEQ ID NO: 2) containing one or more Fcamino acid substitutions. An exemplary, but non-limiting, sequence of heavy chain constant region of human IgG4 encompassing Fc domain of interest with an Fc amino acid substitution is provided as SEQ ID NO: 3. In some embodiments, the Fc substitutions increase the half-life of the IL- 1 IRa antibody. In some embodiments, the Fc substitutions include M252Y, S254T, and / or T256E wherein the position numbers of the amino acid residues are of the EU numbering scheme. In some embodiments, the Fc substitutions include M428L and / or N434S wherein the position numbers of the amino acid residues are of the EU numbering scheme. In some embodiments, the Fc substitutions include L234A, L235A, and / or P329S wherein the position numbers of the amino acid residues are of the EU numbering scheme. In some embodiments, the Fc substitutions include S228P wherein the position numbers of the amino acid residues are of the EU numbering scheme. In exemplary embodiments, the Fc substitutions include S228P, M252Y, S254T, and T256E.

[0049] In some embodiments, the IL- 1 IRa antibodies of the disclosure contain a light chain constant domain. In some embodiments, the light chain constant domain of the IL-1 IRa antibodies is a human K (kappa) or human (lambda) constant domain sequence. An exemplary, but non-limiting, sequence of a human K (kappa) constant domain sequence is provided as SEQ ID NO: 4.RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVY ACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 4)A. Exemplary IL-1 IRa Antibodies - Complementarity Determining Region (CDR) Sequences

[0050] Provided herein are sequences for exemplary IL- 1 IRa antibodies of the disclosure. As referred below, a light chain variable (VL) domain CDR1 region is referred to as LCDR1; a VL CDR2 region is referred to as LCDR2; a VL CDR3 region is referred to as LCDR3; a heavy chain variable (VH) domain CDR1 region is referred to as HCDR1; a VH CDR2 region is referred to as HCDR2; and a VH CDR3 region is referred to as HCDR3. Table 1 provide exemplary CDR triplets for the light chains and heavy chains of IL- 1 IRa antibodies of the disclosure.

[0001] Table 1: Exemplary IL-HRa antibody CDR Combinations

[0051] In some embodiments, the IL-1 IRa antibodies of the disclosure comprise 1, 2, 3, or 4 modifications to any one of the CDRs presented in the CDR sequence combinations of Table 1.

[0052] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0053] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 11, respectively;

[0054] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0055] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 11, respectively;

[0056] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0057] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 11, respectively;

[0058] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 14, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0059] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 15, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0060] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 16, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0061] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 17, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0062] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 18, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0063] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 19, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0064] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 20, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0065] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 21, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0066] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 22, respectively;

[0067] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 23, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0068] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 24, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0069] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 25, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0070] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 26, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0071] In some embodiments, the IL-1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 27, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0072] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 28, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0073] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 29, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0074] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 30, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0075] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 31, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0076] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 32, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0077] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 33, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0078] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 34, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0079] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 35, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0080] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 36, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0081] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 37, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0082] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 38, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively; or

[0083] In some embodiments, the IL- 1 IRa antibody of the disclosure comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 39, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 40, 9, and 10, respectively.B. Exemplary IL-1 IRa Antibodies - Variable Region Sequences

[0084] The term variable region and variable domain are used interchangeably and refer to the portions of the light and heavy chains of an antibody that include the complementarity determining regions and framework regions (FRs).

[0085] Table 2 provides amino acid sequences for the variable domains of exemplary IL- 1 IRa antibodies of the disclosure. Accordingly, in some embodiments an IL-1 IRa antibody of the disclosure comprises a variable heavy chain (VH) comprising an amino acid sequence of any VH sequence listed in Table 2 or at least 70% sequence identity thereto. In some embodiments an IL-1 IRa antibody of the disclosure comprises a variable light chain (VL) comprising an amino acid sequence of any VL sequence listed in Table 2 or at least 70%sequence identity thereto. In some embodiments an IL- 1 IRa antibody of the disclosure comprises a variable heavy chain (VH) comprising an amino acid sequence of any VH sequence listed in Table 2 or at least 70% sequence identity thereto; and comprises a variable light chain (VL) comprising an amino acid sequence of any VL sequence listed in Table 2 or at least 70% sequence identity thereto.

[0086] In some embodiments, an IL-1 IRa antibody of the disclosure comprises the combination of VH / VL variable chain sequences as presented in Table 2.Table 2: Exemplary Variable Heavy Chain and Variable Light Chain Amino Acid Sequences

[0087] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 41 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0088] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 41 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43.

[0089] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 44 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0090] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 44 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43.

[0091] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 45 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0092] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 45 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43.

[0093] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 46 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 46, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0094] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 47 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 47, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0095] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 48 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 48, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0096] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 49 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 49, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0097] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 50 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 50, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0098] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 51 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 51, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0099] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 52 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 52, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0100] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 53 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 53, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0101] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 45 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 54, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 54.

[0102] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 55 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 55, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0103] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 56 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 56, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0104] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 57 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 57, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0105] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 58 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 58, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0106] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 59 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 59, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0107] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 60 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 60, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0108] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 61 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 61, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0109] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 62 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 62, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0110] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 63 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 63, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.[OHl] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 64 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 64, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0112] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 65 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 65, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0113] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 66 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 66, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0114] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 67 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 67, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0115] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 68 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 68, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0116] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 69 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 69, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0117] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 70 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 70, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.

[0118] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the heavy chain variable domain (VH) of the antibody comprises the amino acid sequence of SEQ ID NO: 71 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the light chain variable domain (VL) of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 71, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42.C. Exemplary IL-1 IRa Antibodies - Full-Length Heavy Chain and Light Chain Sequences

[0119] As used herein, the term heavy chain (HC) refers to a polypeptide comprising at least a heavy chain variable region with or without a leader sequence. In some embodiments, the heavy chain comprises at least a portion of a heavy chain constant region.

[0120] As used herein, the term light chain (LC) refers to a polypeptide comprising at least a light chain variable region with or without a leader sequence. In some embodiments, the light chain comprises at least part of a light chain constant region.

[0121] Table 3 provides amino acid sequences for full-length HC / LC of exemplary IL-1 IRa antibodies of the disclosure. The underlined sequence regions of Table 3 denote the signalpeptide sequences. The italicized sequence regions of Table 3 denote the constant domain sequences. Accordingly, in some embodiments an IL-1 IRa antibody of the disclosure comprises a full-length HC comprising an amino acid sequence of SEQ ID NOS: 72, 74, 87, 88, or 89 or at least 70% sequence identity thereto. In some embodiments an IL-1 IRa antibody of the disclosure comprises a full-length LC comprising an amino acid sequence of SEQ ID NO: 73 or at least 70% sequence identity thereto.

[0122] In some embodiments, an IL-1 IRa antibody of the disclosure comprises the combination of full-length HC / LC sequences of mAb5 presented in Table 3. In some embodiments, an IL- 1 IRa antibody of the disclosure consist of the combination of VH / VL variable chain sequences of mAb29 presented in Table 3.Table 3: Exemplary Heavy Chain and Light Chain Amino Acid Sequences

[0123] In some embodiments, provided herein is an IL-1 IRa antibody, wherein the full- length HC of the antibody comprises the amino acid sequence of SEQ ID NO: 72 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the full-length LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the full-length HC of the antibody comprises the amino acid sequence of SEQ ID NO: 72, and the full-length LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73.

[0124] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the full- length HC of the antibody comprises the amino acid sequence of SEQ ID NO: 74 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the full-length LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the full-length HC of the antibody comprises the amino acid sequence of SEQ ID NO: 74, and the full-length LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73.

[0125] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the full- length HC of the antibody comprises the amino acid sequence of SEQ ID NO: 87 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the full-length LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the full-length HC of the antibody comprises the amino acid sequence of SEQ ID NO: 87, and the full-length LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73.

[0126] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the full- length HC of the antibody comprises the amino acid sequence of SEQ ID NO: 88 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the full-length LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the full-length HC of the antibody comprises the amino acid sequence of SEQ ID NO: 88, and the full-length LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73.

[0127] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the full- length HC of the antibody comprises the amino acid sequence of SEQ ID NO: 89 or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the full-length LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the full-length HC of the antibody comprises the amino acid sequence of SEQ ID NO: 89, and the full-length LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73.

[0128] Table 4 provides nucleic acid sequences for full-length HC / LC of exemplary IL-1 IRa antibodies of the disclosure. The underlined sequence regions of Table 4 denote the signal peptide sequences. The italicized sequence regions of Table 4 denote the constant domain sequences. The bolded sequence regions of Table 4 denote the stop codons. Accordingly, in some embodiments an IL- 1 IRa antibody of the disclosure comprises a full-length HC comprising a nucleic acid sequence of SEQ ID NOS: 78 or 80 or at least 70% sequence identity thereto. In some embodiments an IL- 1 IRa antibody of the disclosure comprises a full-length LC comprising a nucleic acid sequence of SEQ ID NO: 79 or at least 70% sequence identity thereto.

[0129] In some embodiments, an IL-1 IRa antibody of the disclosure comprises the combination of full-length HC / LC nucleic acid sequences of mAb5 presented in Table 4. In some embodiments, an IL-1 IRa antibody of the disclosure consist of the combination of VH / VL variable chain nucleic acid sequences of mAb29 presented in Table 4.Table 4: Exemplary Heavy Chain and Light Chain Nucleic Acid Sequences

[0130] In some embodiments, provided herein is an IL-1 IRa antibody, wherein the full- length HC of the antibody is encoded by the nucleic acid sequence of SEQ ID NO: 78 or an nucleic acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the full-length LC of the antibody is encoded by the nucleic acid sequence of SEQ ID NO: 79, or an nucleic acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the full-length HC of theantibody comprises the nucleic acid sequence of SEQ ID NO: 78, and the full-length LC of the antibody comprises the nucleic acid sequence of SEQ ID NO: 79.

[0131] In some embodiments, provided herein is an IL- 1 IRa antibody, wherein the full- length HC of the antibody is encoded by the nucleic acid sequence of SEQ ID NO: 80 or an nucleic acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the full-length LC of the antibody is encoded by the nucleic acid sequence of SEQ ID NO: 79, or an nucleic acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the full-length HC of the antibody comprises the nucleic acid sequence of SEQ ID NO: 80, and the full-length LC of the antibody comprises the nucleic acid sequence of SEQ ID NO: 79.

[0132] In some embodiments, the IL- 1 IRa antibodies of the disclosure have a measurable dissociation constant (KD) of about 60 pM or less. In some embodiments, the IL- 1 IRa antibodies of the disclosure have a measurable dissociation constant (KD) of about 50 pM or less. In some embodiments, the IL-1 IRa antibodies of the disclosure have a measurable dissociation constant (KD) of about 40 pM or less. In some embodiments, the IL- 1 IRa antibodies of the disclosure have a measurable dissociation constant (KD) of about 30 pM or less. In some embodiments, the IL-1 IRa antibodies of the disclosure have a measurable dissociation constant (KD) of about 20 pM or less. In some embodiments, the IL- 1 IRa antibodies of the disclosure have a measurable dissociation constant (KD) of about 10 pM or less. In some embodiments, the IL-1 IRa antibodies of the disclosure have a measurable dissociation constant (KD) of about 1 pM or less.

[0133] In some embodiments, the IL- 1 IRa antibodies of the disclosure inhibit IL-11 induced phosphorylation of signal transducer and activator of transcription 3 (STAT3). In some embodiments, the IL- 1 IRa antibodies of the disclosure inhibit IL-11 induced phosphorylation of extracellular signal-regulated kinase (ERK). In some embodiments, the IL- 1 IRa antibodies of the disclosure inhibit the proliferation of orbital fibroblasts stimulated with IL- 11. In some embodiments, the IL- 1 IRa antibodies of the disclosure inhibit hyaluronan (HA) secretion from orbital fibroblasts stimulated with IL-11. In some embodiments, the IL-1 IRa antibodies of the disclosure inhibit hyaluronan (HA) secretion from orbital fibroblasts stimulated with IGF-1. In some embodiments, the IL-1 IRa antibodies of the disclosureinhibit hyaluronan (HA) secretion from orbital fibroblasts stimulated with both IL-11 and IGF-1. In some embodiments, the IL-1 IRa antibodies of the disclosure inhibit both IL-11 stimulated phosphorylation of STAT3 and IL-11 stimulated HA release by orbital fibroblasts. In some embodiments, the IL- 1 IRa antibodies of the disclosure inhibit procollagen secretion from orbital fibroblasts stimulated with TGFp.D. Exemplary IL-1 IRa Antibodies - Epitope

[0134] In some embodiments, the IL- 1 IRa antibodies of the disclosure bind to a fibronectin type-III domain of human IL-1 IRa, or approximately residues 90-197 of SEQ ID NO: 85. In some embodiments, the IL-1 IRa antibodies bind to the second extracellular domain of IL- HRa.

[0135] In some embodiments, the IL- 1 IRa antibodies of the disclosure bind to an epitope that spans residues 115-134 in in mature IL-1 IRa. In exemplary embodiments, the antibodies of the disclosure which exhibits such binding comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively. In exemplary embodiments, the antibodies of the disclosure which exhibits such binding comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 36, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively. In exemplary embodiments, the antibodies of the disclosure which exhibits such binding comprises the VH sequence of SEQ ID NO: 45, and the VL sequence of SEQ ID NO: 42. In exemplary embodiments, the antibodies of the disclosure which exhibits such binding comprises the VH sequence of SEQ ID NO: 68, and the VL sequence of SEQ ID NO: 42.

[0136] In certain embodiments, the IL-1 IRa antibody, or antigen binding fragment thereof, binds to an epitope comprising the residues ISGLPTRYLTSYRKKTVLGA (SEQ ID NO: 86). In certain embodiments, the IL-1 IRa antibody, or antigen binding fragment thereof, binds to an epitope comprising a subset of residues located within ISGLPTRYLTSYRKKTVLGA (SEQ ID NO: 86). In exemplary embodiments, the antibodies of the disclosure which exhibits such binding comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively. In exemplary embodiments, the antibodies of the disclosure which exhibits such binding comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 36, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively. Inexemplary embodiments, the antibodies of the disclosure which exhibits such binding comprises the VH sequence of SEQ ID NO: 45, and the VL sequence of SEQ ID NO: 42. In exemplary embodiments, the antibodies of the disclosure which exhibits such binding comprises the VH sequence of SEQ ID NO: 68, and the VL sequence of SEQ ID NO: 42.Table 5. Exemplary IL-llRa SequencesII. Treatment of IPF using IL-llRa Antibodies

[0137] Provided herein are antibodies that bind to IL- 1 IRa. The antibodies disclosed herein may be used for the treatment of IPF in a subject. In some embodiments, the subject is human. The subject can be of any age.A. Administration of IL-llRa Antibodies

[0138] As contemplated herein, the IL-1 IRa antibodies of the present disclosure, and pharmaceutical compositions comprising the IL-1 IRa antibodies of the present disclosure are administered for IPF treatment in therapeutically effective amounts.

[0139] Administration of the IL-1 IRa antibodies of the present disclosure may be performed with any suitable pharmaceutically acceptable excipients, carriers, or other agents to provide suitable or improved tolerance, transfer, delivery, and the like.

[0140] In some embodiments, the IL- 1 IRa antibodies of the present disclosure are administered at least once daily. In some embodiments, the IL-1 IRa antibodies of the present disclosure are administered at least once about every 2 days. In some embodiments, the IL- 1 IRa antibodies of the present disclosure are administered at least once about every 3 days. In some embodiments, the IL- 1 IRa antibodies of the present disclosure are administered at least once about every 4 days. In some embodiments, the IL-1 IRa antibodies of the present disclosure are administered at least once about every 5 days. In some embodiments, the IL- 1 IRa antibodies of the present disclosure are administered at least once about every 6 days. In some embodiments, the IL- 1 IRa antibodies of the present disclosure are administered at least once about every week. In some embodiments, the IL- 1 IRa antibodies of the present disclosure are administered at least once about every 2 weeks. In some embodiments, the IL- 1 IRa antibodies of the present disclosure are administered at least once about every 3 weeks. In some embodiments, the IL- 1 IRa antibodies of the present disclosure are administered at least once about every 4 weeks. In some embodiments, the IL-1 IRa antibodies of the present disclosure are administered at least once about every month. In some embodiments, the IL- 1 IRa antibodies of the present disclosure are administered at least once about every 2 months. In some embodiments, the IL-1 IRa antibodies of the present disclosure are administered at least once about every 3 months. In some embodiments, the IL- 1 IRa antibodies of the present disclosure are administered at least once about every 4 months. In some embodiments, the IL- 1 IRa antibodies of the present disclosure are administered at least once about every 5 months. In some embodiments, the IL- 1 IRa antibodies of the present disclosure are administered at least once about every 6 months.

[0141] The administration of the IL-1 IRa antibodies of the present disclosure may be carried out intravenously, subcutaneously, intramuscularly, topically, orally, transdermally, intraperitoneally, intraorbitally, intrathecally, intraventricularly, intranasally, transmucosally, through implantation, through inhalation, or through an on-body device or infuser. Intravenous administration may be carried out via injection or infusion. In exemplary embodiments, the IL-1 IRa antibodies of the present disclosure are administered intravenously. In other exemplary embodiments, the IL- 1 IRa antibodies of the present disclosure are administered subcutaneously.

[0142] In some embodiments, administration of the IL- 1 IRa antibodies of the present disclosure comprises administering one or more doses of the IL- 1 IRa antibody of about 25 mg, of about 50 mg, of about 75 mg, of about 100 mg, of about 150 mg, of about 200 mg, of about 250 mg, of about 300 mg, of about 400 mg, of about 500 mg, of about 600 mg, of about 700 mg, of about 800 mg, of about 900 mg, of about 1000 mg, of about 1100 mg, of about 1200 mg, of about 1300 mg, of about 1400 mg, or of about 1500 mg per dose.

[0143] In some embodiments, administration of the IL- 1 IRa antibodies of the present disclosure comprises administering one or more doses of the IL- 1 IRa antibody of at least about 25 mg, of at least about 50 mg, of at least about 75 mg, of at least about 100 mg, of at least about 150 mg, of at least about 200 mg, of at least about 250 mg, of at least about 300 mg, of at least about 400 mg, of at least about 500 mg, of at least about 600 mg, of at least about 700 mg, of at least about 800 mg, of at least about 900 mg, of at least about 1000 mg, of at least about 1100 mg, of at least about 1200 mg, of at least about 1300 mg, of at least about 1400 mg, or of at least about 1500 mg per dose.

[0144] In some embodiments, administration of the IL- 1 IRa antibodies of the present disclosure comprises administering one or more doses of the IL- 1 IRa antibody of about 25 mg to about 50 mg, of about 25 mg to about 75 mg, of about 25 mg to about 100 mg, of about 25 mg to about 150 mg, of about 25 mg to about 200 mg, of about 25 mg to about 250 mg, of about 25 mg to about 300 mg, of about 25 mg to about 400 mg, of about 25 mg to about 500 mg, of about 25 mg to about 600 mg, of about 25 mg to about 700 mg, of about 25 mg to about 800 mg, of about 25 mg to about 900 mg, of about 25 mg to about 1000 mg, of about 25 mg to about 1100 mg, of about 25 mg to about 1200 mg, of about 25 mg to about 1300 mg, of about 25 mg to about 1400 mg, of about 25 mg to about 1500 mg, of about 50 mg to about 75 mg, of about 50 mg to about 100 mg, of about 50 mg to about 150 mg, of about 50 mg to about 200 mg, of about 50 mg to about 250 mg, of about 50 mg to about 300 mg, of about 50 mg to about 400 mg, of about 50 mg to about 500 mg, of about 50 mg to about 600 mg, of about 50 mg to about 700 mg, of about 50 mg to about 800 mg, of about 50 mg to about 900 mg, of about 50 mg to about 1000 mg, of about 50 mg to about 1100 mg, of about 50 mg to about 1200 mg, of about 50 mg to about 1300 mg, of about 50 mg to about 1400 mg, of about 50 mg to about 1500 mg, of about 75 mg to about 100 mg, of about 75 mg to about 150 mg, of about 75 mg to about 200 mg, of about 75 mg to about 250 mg, of about 75 mg to about 300 mg, of about 75 mg to about 400 mg, of about 75 mg to about 500 mg, of about 75 mg to about 600 mg, of about 75 mg to about 700 mg, of about 75 mg to about 800mg, of about 75 mg to about 900 mg, of about 75 mg to about 1000 mg, of about 75 mg to about 1100 mg, of about 75 mg to about 1200 mg, of about 75 mg to about 1300 mg, of about 75 mg to about 1400 mg, of about 75 mg to about 1500 mg, of about 100 mg to about 150 mg, of about 100 mg to about 200 mg, of about 100 mg to about 250 mg, of about 100 mg to about 300 mg, of about 100 mg to about 400 mg, of about 100 mg to about 500 mg, of about 100 mg to about 600 mg, of about 100 mg to about 700 mg, of about 100 mg to about 800 mg, of about 100 mg to about 900 mg, of about 100 mg to about 1000 mg, of about 100 mg to about 1100 mg, of about 100 mg to about 1200 mg, of about 100 mg to about 1300 mg, of about 100 mg to about 1400 mg, of about 100 mg to about 1500 mg, of about 150 mg to about 200 mg, of about 150 mg to about 250 mg, of about 150 mg to about 300 mg, of about 150 mg to about 400 mg, of about 150 mg to about 500 mg, of about 150 mg to about 600 mg, of about 150 mg to about 700 mg, of about 150 mg to about 800 mg, of about 150 mg to about 900 mg, of about 150 mg to about 1000 mg, of about 150 mg to about 1100 mg, of about 150 mg to about 1200 mg, of about 150 mg to about 1300 mg, of about 150 mg to about 1400 mg, of about 150 mg to about 1500 mg, of about 200 mg to about 250 mg, of about 200 mg to about 300 mg, of about 200 mg to about 400 mg, of about 200 mg to about 500 mg, of about 200 mg to about 600 mg, of about 200 mg to about 700 mg, of about 200 mg to about 800 mg, of about 200 mg to about 900 mg, of about 200 mg to about 1000 mg, of about 200 mg to about 1100 mg, of about 200 mg to about 1200 mg, of about 200 mg to about 1300 mg, of about 200 mg to about 1400 mg, of about 200 mg to about 1500 mg, of about 250 mg to about 300 mg, of about 250 mg to about 400 mg, of about 250 mg to about 500 mg, of about 250 mg to about 600 mg, of about 250 mg to about 700 mg, of about 250 mg to about 800 mg, of about 250 mg to about 900 mg, of about 250 mg to about 1000 mg, of about 250 mg to about 1100 mg, of about 250 mg to about 1200 mg, of about 250 mg to about 1300 mg, of about 250 mg to about 1400 mg, of about 250 mg to about 1500 mg, of about 300 mg to about 400 mg, of about 300 mg to about 500 mg, of about 300 mg to about 600 mg, of about 300 mg to about 700 mg, of about 300 mg to about 800 mg, of about 300 mg to about 900 mg, of about 300 mg to about 1000 mg, of about 300 mg to about 1100 mg, of about 300 mg to about 1200 mg, of about 300 mg to about 1300 mg, of about 300 mg to about 1400 mg, of about 300 mg to about 1500 mg, of about 400 mg to about 500 mg, of about 400 mg to about 600 mg, of about 400 mg to about 700 mg, of about 400 mg to about 800 mg, of about 400 mg to about 900 mg, of about 400 mg to about 1000 mg, of about 400 mg to about 1100 mg, of about 400 mg to about 1200 mg, of about 400 mg to about 1300 mg, of about 400 mg to about 1400 mg, of about 400 mg to about 1500 mg, of about 500 mg toabout 600 mg, of about 500 mg to about 700 mg, of about 500 mg to about 800 mg, of about 500 mg to about 900 mg, of about 500 mg to about 1000 mg, of about 500 mg to about 1100 mg, of about 500 mg to about 1200 mg, of about 500 mg to about 1300 mg, of about 500 mg to about 1400 mg, of about 500 mg to about 1500 mg, of about 600 mg to about 700 mg, of about 600 mg to about 800 mg, of about 600 mg to about 900 mg, of about 600 mg to about 1000 mg, of about 600 mg to about 1100 mg, of about 600 mg to about 1200 mg, of about 600 mg to about 1300 mg, of about 600 mg to about 1400 mg, of about 600 mg to about 1500 mg, of about 700 mg to about 800 mg, of about 700 mg to about 900 mg, of about 700 mg to about 1000 mg, of about 700 mg to about 1100 mg, of about 700 mg to about 1200 mg, of about 700 mg to about 1300 mg, of about 700 mg to about 1400 mg, of about 700 mg to about 1500 mg, of about 800 mg to about 900 mg, of about 800 mg to about 1000 mg, of about 800 mg to about 1100 mg, of about 800 mg to about 1200 mg, of about 800 mg to about 1300 mg, of about 800 mg to about 1400 mg, of about 800 mg to about 1500 mg, of about 900 mg to about 1000 mg, of about 900 mg to about 1100 mg, of about 900 mg to about 1200 mg, of about 900 mg to about 1300 mg, of about 900 mg to about 1400 mg, of about 900 mg to about 1500 mg, of about 1000 mg to about 1100 mg, of about 1000 mg to about 1200 mg, of about 1000 mg to about 1300 mg, of about 1000 mg to about 1400 mg, of about 1000 mg to about 1500 mg, of about 1100 mg to about 1200 mg, of about 1100 mg to about 1300 mg, of about 1100 mg to about 1400 mg, of about 1100 mg to about 1500 mg, of about 1200 mg to about 1300 mg, of about 1200 mg to about 1400 mg, of about 1200 mg to about 1500 mg, of about 1300 mg to about 1400 mg, of about 1300 mg to about 1500 mg, or of about 1400 mg to about 1500 mg. In exemplary embodiments, administration of the IL- 1 IRa antibodies of the present disclosure comprises administering one or more doses of the IL-1 IRa antibody of about 1200mg.

[0145] In some embodiments, the subject is administered one or more priming doses. Without being held to theory or mechanism, the priming dose could act to reduce infusion reaction severity.

[0146] In some embodiments, administration of the IL- 1 IRa antibodies of the present disclosure comprises administering one or more doses of the IL- 1 IRa antibody at a volume of about 0.5mL, of about ImL, of about 2mL, of about 3mL, of about 4mL, of about 5mL, of about lOmL, of about 20mL, of about 30mL, of about 40mL, of about 50mL, of about 60mL, of about 70mL, of about 80mL, of about 90mL, or of about lOOmL per dose.

[0147] In some embodiments, administration of the IL- 1 IRa antibodies of the present disclosure comprises administering one or more doses of the IL- 1 IRa antibody at a volume of at least about 0.5mL, of at least about ImL, of at least about 2mL, of at least about 3mL, of at least about 4mL, of at least about 5mL, of at least about lOmL, of at least about 20mL, of at least about 30mL, of at least about 40mL, of at least about 50mL, of at least about 60mL, of at least about 70mL, of at least about 80mL, of at least about 90mL, or of at least about lOOmL per dose.

[0148] In some embodiments, administration of the IL- 1 IRa antibodies of the present disclosure comprises administering one or more doses of the IL- 1 IRa antibody at a volume of about 0.5 mL to about 1 mL, of about 0.5 mL to about 2 mL, of about 0.5 mL to about 3 mL, of about 0.5 mL to about 4 mL, of about 0.5 mL to about 5 mL, of about 0.5 mL to about 10 mL, of about 0.5 mL to about 20 mL, of about 0.5 mL to about 30 mL, of about 0.5 mL to about 40 mL, of about 0.5 mL to about 50 mL, of about 0.5 mL to about 60 mL, of about 0.5 mL to about 70 mL, of about 0.5 mL to about 80 mL, of about 0.5 mL to about 90 mL, of about 0.5 mL to about 100 mL, of about 1 mL to about 2 mL, of about 1 mL to about 3 mL, of about 1 mL to about 4 mL, of about 1 mL to about 5 mL, of about 1 mL to about 10 mL, of about 1 mL to about 20 mL, of about 1 mL to about 30 mL, of about 1 mL to about 40 mL, of about 1 mL to about 50 mL, of about 1 mL to about 60 mL, of about 1 mL to about 70 mL, of about 1 mL to about 80 mL, of about 1 mL to about 90 mL, of about 1 mL to about 100 mL, of about 2 mL to about 3 mL, of about 2 mL to about 4 mL, of about 2 mL to about 5 mL, of about 2 mL to about 10 mL, of about 2 mL to about 20 mL, of about 2 mL to about 30 mL, of about 2 mL to about 40 mL, of about 2 mL to about 50 mL, of about 2 mL to about 60 mL, of about 2 mL to about 70 mL, of about 2 mL to about 80 mL, of about 2 mL to about 90 mL, of about 2 mL to about 100 mL, of about 3 mL to about 4 mL, of about 3 mL to about 5 mL, of about 3 mL to about 10 mL, of about 3 mL to about 20 mL, of about 3 mL to about 30 mL, of about 3 mL to about 40 mL, of about 3 mL to about 50 mL, of about 3 mL to about 60 mL, of about 3 mL to about 70 mL, of about 3 mL to about 80 mL, of about 3 mL to about 90 mL, of about 3 mL to about 100 mL, of about 4 mL to about 5 mL, of about 4 mL to about 10 mL, of about 4 mL to about 20 mL, of about 4 mL to about 30 mL, of about 4 mL to about 40 mL, of about 4 mL to about 50 mL, of about 4 mL to about 60 mL, of about 4 mL to about 70 mL, of about 4 mL to about 80 mL, of about 4 mL to about 90 mL, of about 4 mL to about 100 mL, of about 5 mL to about 10 mL, of about 5 mL to about 20 mL, of about 5 mL to about 30 mL, of about 5 mL to about 40 mL, of about 5 mL to about 50 mL, of about 5 mL to about 60 mL,of about 5 mL to about 70 mL, of about 5 mL to about 80 mL, of about 5 mL to about 90 mL, of about 5 mL to about 100 mL, of about 10 mL to about 20 mL, of about 10 mL to about 30 mL, of about 10 mL to about 40 mL, of about 10 mL to about 50 mL, of about 10 mL to about 60 mL, of about 10 mL to about 70 mL, of about 10 mL to about 80 mL, of about 10 mL to about 90 mL, of about 10 mL to about 100 mL, of about 20 mL to about 30 mL, of about 20 mL to about 40 mL, of about 20 mL to about 50 mL, of about 20 mL to about 60 mL, of about 20 mL to about 70 mL, of about 20 mL to about 80 mL, of about 20 mL to about 90 mL, of about 20 mL to about 100 mL, of about 30 mL to about 40 mL, of about 30 mL to about 50 mL, of about 30 mL to about 60 mL, of about 30 mL to about 70 mL, of about 30 mL to about 80 mL, of about 30 mL to about 90 mL, of about 30 mL to about 100 mL, of about 40 mL to about 50 mL, of about 40 mL to about 60 mL, of about 40 mL to about 70 mL, of about 40 mL to about 80 mL, of about 40 mL to about 90 mL, of about 40 mL to about 100 mL, of about 50 mL to about 60 mL, of about 50 mL to about 70 mL, of about 50 mL to about 80 mL, of about 50 mL to about 90 mL, of about 50 mL to about 100 mL, of about 60 mL to about 70 mL, of about 60 mL to about 80 mL, of about 60 mL to about 90 mL, of about 60 mL to about 100 mL, of about 70 mL to about 80 mL, of about 70 mL to about 90 mL, of about 70 mL to about 100 mL, of about 80 mL to about 90 mL, of about 80 mL to about 100 mL, or of about 90 mL to about 100 mL.

[0149] In some embodiments, a dose is achieved by a plurality of administrations. Each administration may contain a partial dose, and the administrations may occur sequentially during a single dosing session or over a defined dosing period. In some embodiments, the total dose is divided evenly among administrations. For example, a dose of about 1200mg may be achieved by 4 administrations of about 300mg. In some embodiments, the dose is achieved by at least 2 to about 5 administrations. In some embodiments, the dose is achieved by at least 2 administrations. In some embodiments, the dose is achieved by at least 3 administrations. In some embodiments, the dose is achieved by at least 4 administrations. In some embodiments, the dose is achieved by at least 5 administrations.B. Pharmaceutical Compositions

[0150] The disclosure also provides pharmaceutical compositions comprising any one of the IL-1 IRa antibodies disclosed herein, and optionally a pharmaceutical acceptable excipient or carrier. In some embodiments, the pharmaceutical composition is sterile. The pharmaceutical compositions may be formulated to be compatible with their intended routes ofadministration. In some embodiments, the pharmaceutical compositions of the disclosure are suitable for administration to a human subject.C. Combination Therapies

[0151] The administration of any one of the IL- 1 IRa antibodies provided herein may be in combination with one or more known drugs or treatments for diseases or conditions. In some embodiments, at least one additional IPF therapy is administered during a course of treatment with the IL- 1 IRa antibody. In some embodiments, the at least one additional IPF therapy is an anti-fibrotic. In some embodiments, the at least one additional IPF therapy is Pirfenidone. In some embodiments, the at least one additional IPF therapy is Nintedanib. In some embodiments, the at least one additional IPF therapy is a PDE4 inhibitor, such as Nerandomilast (BI 1015550). In some embodiments, the at least one additional IPF therapy is an Integrin inhibitor (e.g., Bexotegrast (PLN-74809)). In some embodiments, the at least one additional IPF therapy is a hedgehog inhibitor (e.g., ENV-101 (taladegib)).

[0152] In some embodiments, the at least one additional IPF therapy is administered prior to the administration of a single dose of the IL-1 IRa antibodies of the disclosure. In some embodiments, at least one additional IPF therapy is administered simultaneously to the administration of a single dose of the IL- 1 IRa antibodies of the disclosure. In some embodiments, the at least one additional IPF therapy is administered after the administration of a single dose of the IL- 1 IRa antibodies of the disclosure. In some embodiments, at least one additional IPF therapy is administered within the same composition as the IL-1 IRa antibodies of the disclosure. In some embodiments, at least one additional IPF therapy is administered in a separate composition as the IL-1 IRa antibodies of the disclosure. In some embodiments, the at least one additional IPF therapy is administered as a loading dose. In some embodiments, the loading dose occurs for a duration of about 1 to about 6 months.

[0153] The administration of the at least one additional IPF therapy may be carried out intravenously, subcutaneously, intramuscularly, topically, orally, transdermally, intraperitoneally, intraorbitally, intrathecally, intraventricularly, intranasally, transmucosally, through implantation, through inhalation, or through an on-body device or infuser.D. Bispecific antibodies

[0154] The disclosure also provides bispecific antibodies which target IL- 1 IRa and a second target antigen. The bispecific antibody of the disclosure may be generated by any knownmethod in the art. In some embodiments, the bispecific antibody comprises a first antigen binding arm that specifically binds IL-1 IRa and a second antigen binding arm that specifically binds to an IPF associated antigen. In some embodiments, the first antigen binding arm is derived from any one of the IL-1 IRa antibodies of the disclosure.

[0155] In some embodiments, the first antigen binding arm that specifically binds to IL- 1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0156] In some embodiments, the first antigen binding arm that specifically binds to IL- 1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 11, respectively;

[0157] In some embodiments, the first antigen binding arm that specifically binds to IL- 1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and10, respectively;

[0158] In some embodiments, the first antigen binding arm that specifically binds to IL- 1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and11, respectively;

[0159] In some embodiments, the first antigen binding arm that specifically binds to IL- 1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and10, respectively;

[0160] In some embodiments, the first antigen binding arm that specifically binds to IL- 1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and11, respectively;

[0161] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 14, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0162] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 15, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0163] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 16, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0164] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 17, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0165] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 18, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0166] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and19, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0167] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and20, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0168] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 21, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0169] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 22, respectively;

[0170] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 23, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0171] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 24, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0172] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 25, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0173] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 26, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0174] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 27, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0175] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 28, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0176] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 29, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0177] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 30, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0178] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 31, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0179] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 32, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0180] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 33, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0181] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 34, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0182] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 35, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0183] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 36, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0184] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 37, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0185] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 38, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively; or

[0186] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 39, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 40, 9, and 10, respectively.

[0187] In some embodiments, the first antigen binding arm that specifically binds to IL-1 IRa, comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein:

[0188] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0189] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0190] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0191] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0192] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0193] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0194] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 46, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0195] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 47, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0196] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 48, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0197] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 49, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0198] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 50, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0199] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 51, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0200] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0201] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0202] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 54, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0203] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0204] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 56, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0205] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 57, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0206] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 58, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0207] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 59, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0208] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 60, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0209] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 61, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0210] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 62, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0211] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0212] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 64, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0213] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 65, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0214] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 66, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0215] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0216] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0217] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0218] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or

[0219] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%,96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.

[0220] In some embodiments, the IPF associated antigen is selected from the group consisting of a receptor tyrosine kinase (RTK) such as vascular endothelial growth factor (VEGF), fibroblast growth factor receptor (FGFR), and Platelet-derived growth factor receptor (PDGFR), PDE4, integrin, hedgehog, and connective tissue growth factor (CTGF). In some embodiments, the second antigen binding arm comprises a VH and a VL sequence that binds a receptor tyrosine kinase (RTK) such as vascular endothelial growth factor (VEGF), fibroblast growth factor receptor (FGFR), and Platelet-derived growth factor receptor (PDGFR), PDE4, integrin, hedgehog, or connective tissue growth factor (CTGF). In some embodiments, the second antigen binding arm is derived from pamrevlumab.E. Antibody-drug conjugates

[0221] The disclosure also provides antibody-drug conjugates (ADCs). ADCs generally comprise: an antibody or antigen binding fragment, a small molecule drug and an optional linker coupling the antibody or antigen binding fragment and the drug. In some embodiments, the linker is a cleavable linker. In some embodiments, the ADC comprises any one of the IL- 1 IRa antibodies of the disclosure linked to a therapeutic drug. In some embodiments, the therapeutic drug is an anti-fibrotic agent. In some embodiments, the IPF therapeutic drug is Pirfenidone. In some embodiments, the therapeutic drug is Nintedanib. In some embodiments, the IPF therapeutic drug is a PDE4 inhibitor, such as Nerandomilast (BI 1015550). In some embodiments, the IPF therapeutic drug is a PI3K / mT0R inhibitor (e.g., Omipalisib). In some embodiments, the IPF therapeutic drug is an Integrin inhibitor (e.g., PLN-74809). In some embodiments, the IPF therapeutic drug is a hedgehog inhibitor (e.g., ENV-101).

[0222] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0223] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 11, respectively;

[0224] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0225] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 11, respectively;

[0226] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0227] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 11, respectively;

[0228] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 14, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0229] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 15, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0230] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 16, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0231] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 17, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0232] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 18, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0233] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 19, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0234] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 20, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0235] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 21, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0236] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 22, respectively;

[0237] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 23, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0238] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 24, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0239] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 25, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0240] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 26, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0241] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 27, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0242] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 28, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0243] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 29, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0244] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 30, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0245] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 31, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0246] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 32, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0247] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 33, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0248] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 34, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0249] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 35, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0250] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 36, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0251] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 37, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively;

[0252] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 38, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 8, 9, and 10, respectively; or

[0253] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 39, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 40, 9, and 10, respectively

[0254] In some embodiments, IL- 1 IRa antibody linked to the therapeutic drug, comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein:

[0255] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0256] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0257] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0258] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0259] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0260] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0261] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 46, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0262] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 47, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0263] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 48, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0264] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 49, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0265] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 50, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0266] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 51, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0267] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0268] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0269] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 54, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0270] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0271] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 56, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0272] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 57, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0273] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 58, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0274] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 59, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0275] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 60, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0276] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 61, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0277] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 62, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0278] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0279] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 64, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0280] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 65, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0281] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 66, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0282] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0283] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0284] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0285] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or

[0286] the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.

[0287] In some embodiments, the IL- 1 IRa antibodies of the disclosure used in the ADC function as a therapeutic agent. In some embodiments, the IL- 1 IRa antibodies of the disclosure used in the ADC function as a delivery agent, delivering the conjugated drug to an IL-1 IRa expressing cell. In some embodiments, the IL-1 IRa antibodies of the disclosure used in the ADC function as both a therapeutic agent and as a delivery agent, delivering the conjugated drug to an IL- 1 IRa expressing cell.Enumerated Embodiments

[0288] The following non-limiting enumerated embodiments are provided as exemplary.

[0289] Embodiment 1. A method of treating idiopathic pulmonary fibrosis (IPF) in a human subject in need thereof, comprising administering to the subject one or more dose(s) of about 300 mg to about 1200 mg per dose of an antibody which binds to human interleukin- 11 receptor subunit a (IL- 1 IRa).

[0290] Embodiment 2. The method of Embodiment 1, wherein the IL-1 IRa antibody comprises a heavy chain complementarity determining region (HCDR) 1, HCDR2, and HCDR3, and a light chain complementarity determining region (LCDR) 1, LCDR2, and LCDR3, wherein:

[0291] a) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0292] b) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively;

[0293] c) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0294] d) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively;

[0295] e) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0296] f) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively;

[0297] g) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 14, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0298] h) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 15, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0299] i) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 16, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0300] j) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 17, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0301] k) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 18, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0302] 1) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 19, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0303] m) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 20, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0304] n) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 21, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0305] o) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 22, respectively;

[0306] p) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 23, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0307] q) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 24, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0308] r) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 25, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0309] s) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 26, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0310] t) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 27, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0311] u) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 28, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0312] v) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 29, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0313] w) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 30, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0314] x) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 31, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0315] y) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 32, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0316] z) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 33, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0317] aa) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 34, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0318] bb) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 35, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0319] cc) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 36, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0320] dd) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 37, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0321] ee) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 38, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; or

[0322] ff) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 39, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 40, 9, and 10, respectively.

[0323] Embodiment 3. The method of Embodiment 1 or Embodiment 2, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein:

[0324] a) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%,85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0325] b) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0326] c) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0327] d) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0328] e) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0329] f) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0330] g) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 46, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0331] h) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 47, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0332] i) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 48, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0333] j) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 49, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%,79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0334] k) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 50, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0335] 1) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 51, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0336] m) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0337] n) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibodycomprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0338] o) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 54, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0339] p) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0340] q) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 56, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0341] r) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 57, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%,85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0342] s) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 58, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0343] t) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 59, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0344] u) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 60, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0345] v) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 61, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0346] w) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 62, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0347] x) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0348] y) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 64, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0349] z) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 65, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0350] aa) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 66, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%,79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0351] bb) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0352] cc) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0353] dd) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0354] ee) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibodycomprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or

[0355] ff) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.

[0356] Embodiment 4. The method of any one of Embodiment 1 -Embodiment 2, wherein the IL- 1 IRa antibody is a full-length antibody.

[0357] Embodiment 5. The method of any one of Embodiment 1 -Embodiment 2, wherein the IL- 1 IRa antibody is an antibody fragment.

[0358] Embodiment 6. The method of any one of Embodiment 1 -Embodiment 5, wherein the IL-1 IRa antibody comprises an Fc domain.

[0359] Embodiment 7. The method of Embodiment 6, wherein the Fc domain is selected form the group consisting of human IgGl, IgG2, IgG3, and IgG4 heavy chain sequence.

[0360] Embodiment 8. The method of Embodiment 7, wherein the Fc domain comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.

[0361] Embodiment 9. The method any one of Embodiment 6-Embodiment 8, wherein the Fc domain comprises one or more amino acid substitutions.

[0362] Embodiment 10. The method of Embodiment 9, wherein the one or more amino acid substitutions comprises a S228P substitution, wherein the position number of the amino acid residue is of the EU numbering scheme.

[0363] Embodiment 11. The method of Embodiment 9 or Embodiment 10, wherein the one or more amino acid substitutions extend the IL-1 IRa antibody’s half-life.

[0364] Embodiment 12. The method of any one of Embodiment 9-Embodiment 11, wherein the one or more amino acid substitutions are selected from the group consisting of M252Y, S254T, and T256E substitutions, wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0365] Embodiment 13. The method of any one of Embodiment 9-Embodiment 12, wherein the one or more amino acid substitutions are selected from the group consisting of M428L and N434S substitutions, wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0366] Embodiment 14. The method of Embodiment 9, wherein the one or more amino acid substitutions are selected from the group consisting of L234A, L235A, and P329S substitutions, wherein the position numbers of the amino acid residues are of the EU numbering scheme.

[0367] Embodiment 15. The method of any one of Embodiment 1 -Embodiment 14, wherein the antibody comprises a heavy chain (HC) and a light chain (LC), wherein:

[0368] a) the HC of the antibody comprises the amino acid sequence of SEQ ID NO: 72, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0369] b) the HC of the antibody comprises the amino acid sequence of SEQ ID NO: 74, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0370] c) the HC of the antibody comprises the amino acid sequence of SEQ ID NO: 87, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0371] d) the HC of the antibody comprises the amino acid sequence of SEQ ID NO: 88, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or

[0372] e) the HC of the antibody comprises the amino acid sequence of SEQ ID NO: 89, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.

[0373] Embodiment 16. The method of any one of Embodiment 1 -Embodiment 15, wherein the antibody wherein the antibody comprises a heavy chain (HC) and a light chain (LC), wherein:

[0374] a) the HC of the antibody is encoded by the nucleic acid sequence of SEQ ID NO: 78 or an nucleic acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the LC of the antibody is encoded by the nucleic acid sequence of SEQ ID NO: 79, or an nucleic acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or

[0375] b) the HC of the antibody is encoded by the nucleic acid sequence of SEQ ID NO: 80 or an nucleic acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the LC of the antibody is encoded by the nucleic acid sequence of SEQ ID NO: 79, or an nucleic acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%,82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.

[0376] Embodiment 17. The method of any one of Embodiment 1 -Embodiment 16, wherein the dose is administered daily, weekly, about every two weeks, about every three weeks, about every four weeks, every month, or every two months.

[0377] Embodiment 18. The method of any one of Embodiment 1-Embodiment 17, wherein the dose is administered intravenously.

[0378] Embodiment 19. The method of any one of Embodiment 1-Embodiment 17, wherein the dose is administered subcutaneously.

[0379] Embodiment 20. The method of any one of Embodiment 1-Embodiment 19, wherein the dose is achieved by at least 2 to about 5 administrations.

[0380] Embodiment 21. The method of any one of Embodiment 1-Embodiment 19, wherein the dose is administered at a volume of about 1 mL, about 2 mL, about 3 mL or about 4 mL.

[0381] Embodiment 22. The method of any one of Embodiment 1-Embodiment 19, wherein the dose is administered at a volume of about 1 mL to about 25 mL.

[0382] Embodiment 23. The method of any one of Embodiment 1-Embodiment 13, wherein a dose of about 1200 mg is administered intravenously to the subject at a volume of about 60 mL about every four weeks.

[0383] Embodiment 24. The method of any one of Embodiment 1-Embodiment 23, wherein the dissociation constant (KD) of the IL- 1 IRa antibody to human IL- 1 IRa is less than about 50 pM.

[0384] Embodiment 25. The method of any one of Embodiment 1-Embodiment 24, wherein the IL-1 IRa antibody does not bind to mouse IL-1 IRa or rat IL-1 IRa.

[0385] Embodiment 26. The method of any one of Embodiment 1-Embodiment 25, wherein the IL- 1 IRa antibody inhibits IL-11 induced phosphorylation of STAT3.

[0386] Embodiment 27. The method of any one of Embodiment 1-Embodiment 26, wherein the IL- 1 IRa antibody inhibits IL-11 induced phosphorylation of ERK.

[0387] Embodiment 28. The method of any one of Embodiment 1-Embodiment 27, wherein the IL- 1 IRa antibody inhibits procollagen release.

[0388] Embodiment 29. The method of any one of Embodiment 1-Embodiment 28, wherein an additional IPF therapy is administered during a course of treatment with the IL- 11 Ra antibody.

[0389] Embodiment 30. The method of Embodiment 29, wherein the additional IPF therapy is administered concurrently with the administration of the IL-1 IRa antibody.

[0390] Embodiment 31. The method of Embodiment 29, wherein the additional IPF therapy is administered after the administration of the IL- 1 IRa antibody.

[0391] Embodiment 32. The method of Embodiment 29, wherein the additional IPF therapy is administered prior to the administration of the IL-1 IRa antibody.

[0392] Embodiment 33. The method of any one of Embodiment 29-Embodiment 32, wherein the additional IPF therapy is selected from the group consisting of an anti-fibrotic, Pirfenidone, Nintedanib, PDE4 inhibitor (e.g., Nerandomilast (BI 1015550)), an Integrin inhibitor (e.g., Bexotegrast (PLN-74809)), and a hedgehog inhibitor (e.g., ENV-101 (taladegib)).

[0393] Embodiment 34. The method of any one of Embodiment 29-Embodiment 33, wherein the at least one additional IPF therapy is administered intravenously, subcutaneously, intramuscularly, topically, orally, transdermally, intraperitoneally, intraorbitally, intrathecally, intraventricularly, intranasally, transmucosally, through implantation, through inhalation, or through an on-body device or infuser.

[0394] Embodiment 35. A bispecific antibody comprising:

[0395] a) a first antigen binding arm that specifically binds to IL- 1 IRa, comprising a heavy chain complementarity determining region (HCDR) 1, HCDR2, and HCDR3, and a light chain complementarity determining region (LCDR) 1, LCDR2, and LCDR3, wherein:

[0396] i) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0397] ii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively;

[0398] iii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0399] iv) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively;

[0400] v) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0401] vi) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively;

[0402] vii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 14, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0403] viii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 15, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0404] ix) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 16, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0405] x) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 17, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0406] xi) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 18, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0407] xii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 19, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0408] xiii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 20, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0409] xiv) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 21, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0410] xv) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 22, respectively;

[0411] xvi) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 23, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0412] xvii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 24, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0413] xviii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 25, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0414] xix) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 26, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0415] xx) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 27, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0416] xxi) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 28, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0417] xxii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 29, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0418] xxiii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 30, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0419] xxiv) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 31, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0420] xxv) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 32, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0421] xxvi) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 33, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0422] xxvii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 34, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0423] xxviii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 35, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0424] xxix) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 36, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0425] xxx) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 37, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0426] xxxi) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 38, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; or

[0427] xxxii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 39, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 40, 9, and 10, respectively; and

[0428] b) a second antigen binding arm that specifically binds to an IPF associated antigen.

[0429] Embodiment 36. The bispecific antibody of Embodiment 35, wherein the first antigen binding arm comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein:

[0430] a) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0431] b) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%,95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0432] c) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0433] d) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0434] e) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0435] f) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with atleast 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0436] g) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 46, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0437] h) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 47, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0438] i) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 48, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0439] j) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 49, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%,85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0440] k) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 50, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0441] 1) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 51, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0442] m) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0443] n) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0444] o) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 54, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0445] p) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0446] q) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 56, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0447] r) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 57, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0448] s) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 58, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%,79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0449] t) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 59, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0450] u) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 60, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0451] v) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 61, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0452] w) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 62, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibodycomprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0453] x) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0454] y) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 64, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0455] z) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 65, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0456] aa) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 66, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%,85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0457] bb) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0458] cc) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0459] dd) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0460] ee) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or

[0461] ff) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.

[0462] Embodiment 37. The bispecific antibody of Embodiment 35 or Embodiment 36, wherein the IPF associated antigen is selected from the group consisting of a receptor tyrosine kinase (RTK) such as vascular endothelial growth factor (VEGF), fibroblast growth factor receptor (FGFR), and Platelet-derived growth factor receptor (PDGFR), PDE4, integrin, hedgehog, and connective tissue growth factor (CTGF).

[0463] Embodiment 38. The bispecific antibody of any one of Embodiment 35-Embodiment 37, wherein the second antigen binding arm comprises a VH and a VL sequence derived from pamrevlumab.

[0464] Embodiment 39. An antibody-drug conjugate (ADC) comprising:

[0465] a) an antibody that specifically binds to IL-1 IRa, wherein the antibody comprising a heavy chain complementarity determining region (HCDR) 1, HCDR2, and HCDR3, and a light chain complementarity determining region (LCDR) 1, LCDR2, and LCDR3, wherein:

[0466] i) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0467] ii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively;

[0468] iii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0469] iv) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively;

[0470] v) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0471] vi) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively;

[0472] vii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 14, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0473] viii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 15, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0474] ix) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 16, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0475] x) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 17, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0476] xi) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 18, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0477] xii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 19, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0478] xiii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 20, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0479] xiv) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 21, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0480] xv) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 22, respectively;

[0481] xvi) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 23, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0482] xvii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 24, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0483] xviii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 25, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0484] xix) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 26, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0485] xx) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 27, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0486] xxi) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 28, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0487] xxii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 29, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0488] xxiii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 30, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0489] xxiv) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 31, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0490] xxv) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 32, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0491] xxvi) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 33, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0492] xxvii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 34, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0493] xxviii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 35, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0494] xxix) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 36, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0495] xxx) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 37, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;

[0496] xxxi) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 38, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; or

[0497] xxxii) the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 39, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 40, 9, and 10, respectively;

[0498] b) a linker; and

[0499] c) an IPF therapeutic drug.

[0500] Embodiment 40. The ADC of Embodiment 39, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein:

[0501] a) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0502] b) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibodycomprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0503] c) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0504] d) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0505] e) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0506] f) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%,85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0507] g) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 46, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0508] h) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 47, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0509] i) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 48, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0510] j) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 49, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0511] k) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 50, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0512] 1) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 51, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0513] m) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0514] n) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0515] o) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%,79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 54, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0516] p) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0517] q) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 56, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0518] r) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 57, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0519] s) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 58, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibodycomprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0520] t) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 59, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0521] u) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 60, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0522] v) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 61, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0523] w) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 62, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%,85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0524] x) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0525] y) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 64, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0526] z) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 65, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0527] aa) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 66, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0528] bb) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0529] cc) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0530] dd) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;

[0531] ee) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or

[0532] ff) the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%,I l l79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.

[0533] Embodiment 41. The ADC of Embodiment 39 or Embodiment 40, wherein the IPF therapeutic drug is selected from the group consisting of an anti-fibrotic, Pirfenidone, Nintedanib, a PDE4 inhibitor, such as Nerandomilast (BI 1015550), a PI3K / mTOR inhibitor (e.g., Omipalisib), an Integrin inhibitor (e.g., PLN-74809), and a hedgehog inhibitor (e.g., ENV-101).

[0534] Embodiment 42. The ADC of any one of Embodiment 39-Embodiment 41, wherein the linker is a cleavable linker.

[0535] Embodiment 43. Use of an antibody which binds to human interleukin- 11 receptor subunit a (IL- 1 IRa) in the manufacture of a medicament for treating idiopathic pulmonary fibrosis (IPF) in a human subject in need thereof, wherein the antibody is administered to the subject in one or more dose(s) of about 300 mg to about 1200 mg per dose.

[0536] Embodiment 44. An antibody which binds to human interleukin- 11 receptor subunit a (IL- 1 IRa) for use in the treatment of idiopathic pulmonary fibrosis (IPF) in a human subject in need thereof, wherein the antibody is administered to the subject in one or more dose(s) of about 300 mg to about 1200 mg per dose.

[0537] The following examples are included for illustrative purposes only and are not intended to limit the scope of the invention.EXAMPLESExample 1: mAb5 Lung Antifibrotic Characterization

[0538] mAb5 (SEQ ID NOS: 72 and 73 of Table 3) binding, potency and lung antifibrotic activity were characterized as summarized in FIG. 1. For mAb5 direct binding, ELISA plates (Nunc, MaxiSorp) were coated with 2 pg / mL of soluble IL-11R or other antigens in PBS over-night. After blocking with 2% BSA in PBS plates were washed and mAb5 was serially diluted in sample conjugate buffer (50 mM Tris, 0.14 M NaCl, 1% BSA, 0.05% Tween 20,adjusted to pH7.0) across the plate starting at 2 pg / mL. After an hour incubation on a plate shaker, plates were washed and HRP conjugated goat anti-human IgG, Fc specific (Jackson ImmunoResearch Laboratories #109-035-098) was added at 1 / 10,000 dilution. After a further hour incubation, plates were washed again and developed by addition of Ultra-TMB HRP substrate. Reactions were stopped using sulfuric acid, and absorbance at 450 nm measured.

[0539] For Biolayer Interferometry (Octet) analysis, binding kinetic measurements were taken on a Fortebio Octet RED96e instrument. mAb5 was loaded onto anti-human constant domain (AHC) biosensors (ForteBio) in lOx kinetics buffer consisting of PBS, 0.1% BSA, 0.02% Tween 20 for 120 seconds to achieve a spectral shift value of 0.8 to 1.2 nm. Association was carried out in the presence of a 2-fold dilution series of hIL-1 IRa and was allowed to proceed for 120 seconds; dissociation was measured for 300 to 1200 seconds. Dilution series started at 100 nM for weaker variants or 10 nM for the most potent mAbs.

[0540] For pSTAT3 and pERK assays in DLD-1 cells, DLD-1 cells were purchased from ATCC (cat. no. CCL-221) and then grown and passaged as recommended by the vendor. For the assay, cells were plated in full growth media (RPMI Thermo Fisher cat. no. 61870036 + 10% FBS + lx pen / strep) at 5 x 105 cells per well in a 6-well plate and allowed to attach over-night. Media was then removed, cells were washed once with PBS, and switched into 1.35 mL of starvation media (RPMI + 0.1% BSA) for 18-24 hours. On the day of the assay, 150 pL of mAb5 was added in a serial dilution series to each well of the 6-well plate. Assays were run using 6 - 8 different concentrations to generate an inhibition curve. After 30 minutes of pre-incubation with test article, cells were stimulated with either 50 ng / mL of IL- 11 or 100 ng / mL of hyper IL-11 depending upon the assay and incubated for 30 minutes prior to lysis. For lysis, cells were washed once with 2 mL of ice-cold PBS before addition of 400 pL of lysis buffer (Thermo Fisher cat. no. FNN0071) containing 1 x HALT protease and phosphatase inhibitor (LifeTechnol ogies cat. no. 78441) was added to the cell monolayer. Cells were incubated with lysis buffer for 5 minutes on ice before lysates were transferred into Eppendorf tubes and spun at maximum speed (>16k rpm) at 4 °C for 5 minutes. Lysate samples were then transferred to a new Eppendorf tube leaving the pellet behind to be discarded. The phosphoSTAT3 ELISA was performed using the human / mouse phospho- STAT3 (Y705) DuoSet from R&D systems (cat. no. DYC4607B-2) according to manufacturer specifications. In brief, plates were coated with 6 pg / mL Human / Mouse Phospho-STAT3 (Y705) Capture Antibody (Part 842631) at 4 °C over-night. After 3 washesusing wash buffer (PBS + 0.05% Tween 20), plates were then blocked by addition of PBS containing 1% BSA + 0.05% sodium azide for 1 - 2 hours at room temperature. Plates were then washed 3 times in wash buffer prior to addition of lysate samples or standards. Cell lysate was added neat to the coated plate, and diluent #3 alone was also added to the plate as the zero standard. Plates were sealed and incubated with samples or standards for 2 hours at room temperature on a shaking incubator at 600RPM followed by washing 3 times with wash buffer. Detection antibody (Part #842632) was diluted to 100 ng / mL in the manufacturer provided Diluent 1 before 100 pL per well was added to the plate. Plates were incubated with detection antibody for 2 hours at room temperature. Plates were then washed 3 times in wash buffer before 100 pL of streptavidin A diluted 1 :200 in Diluent 1 was added to each well. The plate was then incubated for 20 minutes at room temperature in the dark. Plates were subsequently washed 3 times in wash buffer before adding 100 pL per well of Ultra TMB (Thermo Fisher cat. no. 34028) to visualize. Reaction was stopped after sufficient development by adding 50 pL per well of 2 M sulfuric acid stop solution. Plates were read at 450 nm with wavelength correction at 540 nm on a SpectraMax iD5 plate reader (Molecular Devices). The phospho-ERKl (T202 / Y204) was similarly performed using the Phospho- ERKl (T202 / Y204) / ERK2 (T185 / Y187) DuoSet IC ELISA kit (R&D Systems cat. no. DYC101B-2). For this assay plates were coated with 4 pg / mL Human / Mouse Phospho-ERKl (T202 / Y204) Capture Antibody (Part 841452), and 500 ng / mL Human / Mouse Phospho- ERKl Detection Antibody (Part 841453) was used for detection. All other steps in the assay protocol were identical to human phospho-STAT3 detection described above.

[0541] For dermal fibroblasts pSTAT3 assays, primary human skin fibroblasts (Cell Applications Inc.; cat # 106-05a) were cultured in fibroblast growth media growth media (DMEM; Gibco cat# 10569-010) containing 10% FBS and 1% penicillin / Streptomycin. For experiments, dermal fibroblasts (5,000 cells / well) were plated in a black, clear bottom 96 well plate (Corning Costar; cat# 3603) in 0.1 mL of fibroblast growth media and allowed to attach over-night. Next, growth media was decanted and 0.1 mL of starvation media (DMEM + 1% penicillin / streptomycin without FBS) was added over-night. Following the starvation period, media was decanted and cells were pre-incubated for 1 hr with increasing concentrations with mAb5 or isotype controls (0.001 -3000 pg / mL) in a 0.1 mL volume. Cells were then stimulated for 15 min (human dermal fibroblasts and NIH / 3T3 cells) or 30 min (fHDF / TERT166) at 37 OC in a humidified CO2 controlled incubator with eitherrecombinant human IL11 (Life Technologies; cat# PHC0115) or mouse IL11 (Biolegend; cat #756104), respectively.

[0542] TGFp is known to stimulate fibroblasts to produce collagen and other molecules to provide structural support to tissues. In the context of fibrosis, the excessive production of collagen and other molecules leads to the formation of scar tissue. To assess the effects of mAb5 on TGFP induced collagen production, IPF fibroblasts (Lonza cat# CC-7231; Donor 8F5049; a.k.a. IPF049) were cultured using the FGM-2 Fibroblast Growth Medium-2 BulletKit (Lonza cat# CC-3132) on plates coated with reduced Growth Factor Cultrex Basement Membrane Extract, PathClear (R&D systems; cat# 3433-005-01). Once confluent, IPF cells were plated at 5,000 cells per well in a black, clear bottom 96 well plate (Corning Costar; cat# 3603) coated with Cultrex RGF and allowed to attach over-night. The next day, the plate was decanted, replaced with new FGM-2 media and cells were pre-treated for 1 hr with mAb5 (0.03 -

[0543] 30 pg / mL); mL; 0.2 - 200 nM). Following the antibody pre-incubation, 5 ng / mL of recombinant human TGFpi (R&D systems; cat# 240-B-010 / CF) was added to each well and cells were allowed to incubate with treatment conditions for an additional 48 hr. Wells containing media or TGFpi (no mAb5) served as stimulation and baseline controls.Following the stimulation period, media was removed, and cells were fixed for 10 min with 10% buffered neutral formalin. After fixation, cells were incubated with Glycine (100 mM, pH=7.4) for 10 min to quench free aldehydes and then permeabilized in 0.1% Triton X 100 / PBS for 10 min. Cells were then blocked for 1 hr with PBS / 0.1% tween 20 / 1% BSA at room temperature and then stained using antibodies to collagen type I (Abeam cat# ab260043; 1 :250 dilution) and nuclear staining with Hoechst. Next, cells were washed 2 times with PBS / 0.1% Tween 20 and wells were then filled with 200 pL of PBS for imaging on a Biotek Cytation 5 imaging system with a 4x objective. Collagen staining was measured as the total intensity of collagen positive cells in a 4x field and normalized to cell count based on Hoechst nuclear staining. Expression data were then expressed as the percent inhibition of TGFpi -stimulated collagen I expression at increasing concentrations of mAb5. TGFP induced ~3.5-fold increase in collagen type I secretion by IPF fibroblasts, while mAb5 (200 nM) reduced TGFP-stimulated collagen by -50% (FIG. 2).

[0544] Additionally, PRO-C6 was measured in human IPF lung tissue after the tissue was treated with mAb5, demonstrating a reduction of type VI collagen formation (FIG. 3). To dothis, PCLS was generated using tissue from pulmonary fibrosis patients that underwent lung transplantation. The use of tissue from pulmonary fibrosis patients was coordinated in close collaboration with Prof. A. Prasse (Fraunhofer ITEM) and Prof. D. Jonigk (Pathology department, Hannover Medical School [MHH]). Human lung tissue was provided from a fibrosis patient who underwent lung dissection at the MHH in Germany. The patient gave written informed consent and all information regarding the identity of the patient was anonymized. The experiments with human lung tissue were approved by the ethics committee of the MHH. Only fibrotic lung tissue as qualified by medical pathologists was used for the experiments. Tissue was processed immediately on the day of resection. Tissue slices were prepared from the subpleural and central region of the fibrotic lung from a human endstage donor with pulmonary fibrosis (IPF and secondary fibrosis), as described below. Adjacent tissue cores were used to achieve serial PCLS for the analysis of one treatment as compared to growth medium treated PCLS from the same cores. The use of two lung regions enables the comparison of densely packed fibrotic areas with fibrotic foci with less affected areas. Lung lobes were cannulated and filled with 37 °C warm 2% low melting agarose / medium solution. Filled lobes were cooled on ice. Tissue cores with a diameter of 8 mm were prepared and cut into approximately 300 pm thick slices using a microtome (Krumdieck tissue slicer, Alabama Research and Development, Muniford, AL, USA or Vibratome OTS5000, Science Services GmbH, Munich) in Earle’s Balanced Salts Solution (EBSS). Tissue slices were incubated in Dulbecco’s modified Eagle’s medium / nutrient mixture F12 Ham (DMEM) with Lglutamine and 15 mM HEPES without phenol red. Tissue slices were transferred into petri dishes and washed with DMEM for 2 hours. Medium was changed four times every 30 minutes to remove leftover cell debris. Two PCLS per well were left over night in 500 pL DMEM in 24well plates for a final washing step. Next day, PCLS were treated with mAb5 or controls (see Table 1) in 250pl DMEM / F12 culture medium for 48 hours under normal cell culture conditions (37°C, 5% CO2). Medium contained 100 units / mL penicillin and 100 pg / mL streptomycin and was not supplemented with fetal calf serum.

[0545] After incubation for 48 hours, supernatants were collected, proteinase inhibitor cocktail (0.2%) was added and samples were frozen to 80°C. Additionally, the two PCLS from each well were transferred to a 2 mL safelock tube with 500 pL RNAlater. Following over-night incubation at 4°C, RNAlater was removed and samples stored at 80°C. Samples from the three replicates for each condition were not pooled. The viability and responsiveness of the tissue to immune stimulators was confirmed in a quality control sample where PCLS was incubated with the mitogen 100 ng / mL lipopolysaccharide (LPS). Following 48 hoursincubation, assessment of viability by lactate dehydrogenase (LDH) activity and proinflammatory response by ILip was performed. PROC6 in conditioned media was then analyzed. PRO-C6 (C-terminal of type VI collagen C5 domain released as type VI collagen is incorporated into the matrix; measured on mesoscale platform [hsPROC6]): Reflects type VI collagen formation. Type VI collagen is a beaded filament collagen mainly found in the interface between the interstitial matrix and the basement membrane. Biomarker data are expressed as the percent change (reduction) in PRO-C6 secretion relative to untreated control tissue. The approved IPF drug, nintedanib, was included as a positive control.

[0546] To induce pulmonary fibrosis, mice received 1.5U / kg of bleomycin via oropharyngeal route on day 0. Group 1 animals did not receive bleomycin, instead, they received a single dose of PBS via the oropharyngeal route. Prophylactic treatment began on day -3 before disease induction and continued until the end of the study.

[0547] Bleomycin (15U) was formulated from a sealed bottle was resuspended in 1 mL of PBS. A fresh stock solution of 15 U / mL bleomycin was used and diluted in PBS to prepare a dose of 1.5 U / kg in 70 pl volume for each mouse. The method for instilling bleomycin in mice was described in Current Protocols in Pharmacology: 5.46.1, entitled “Mouse Models of Bleomycin-induced Pulmonary Fibrosis”. Briefly, mice were anesthetized with Isoflurane inhalant anesthesia. The animal was then suspended on its back at an approximately 60 degree angle with a rubber band running under the upper incisors on an inclined surface (Biolite RIS-100, small animal intubation system, Braintree Scientific, Braintree, MA). The airway was opened while securing the tongue, which was held with one arm of padded forceps. 70 pl volume of bleomycin was then administered into the back of the oral cavity with a syringe using a blunt needle. The animal’s tongue and mouth were held open until the liquid disappeared from the oral cavity. The animal was then returned to its cage and monitored until fully recovered from the anesthesia. Treatments were as show in Table El.Table El : Bleomycin-induced Pulmonary Fibrosis Treatment Protocol

[0548] Upon study termination, study animals were anesthetized with isoflurane inhalant anesthesia. The lungs from each animal were harvested and each lung was dissected from the animal and weighed. Weight was recorded. Lungs were snap frozen and stored at -80°C for hydroxyproline assay assessment which demonstrated a significant dose-dependent anti- fibrotic effect by an exemplary anti-IL-1 IRa antibody of the disclosure (FIG. 4), * p<0.01; by one way ANOVA w / Dunnett’s post test. Data from n=10 mice per treatment group. Pirfenidone dosed at 100 mg / kg BID.Example 2: mAb5 Human Pharmacokinetic (PK) and Safety Study

[0549] PK modeling was utilized to predict the mAb5 therapeutic window in humans. Previous in vitro PCLS studies in IPF diseased tissue indicate a maximally efficacious dose of 3 pg / mL. A conservative extrapolation of a 10: 1 biodistribution serumdung, was used, suggesting a 30 pg / mL serum concentration for therapeutic effect in humans. The resulting PK modeling estimated that a 300 mg dose would result in serum concentrations at or above the 30 pg / ml dose in PCLS and dosing timing based on half-life indicate a 2nddose requirement after two weeks and monthly doses thereafter (FIG. 5).

[0550] To determine PK, safety, and target engagement of mAb5 in human subjects, placebo controlled single ascending does (SAD) and multiple ascending dose (MAD) studies were performed in healthy volunteers. A schematic of the study is shown in FIG. 6.

[0551] The SAD study consisted of 5 cohorts with 8 subjects per cohort at a 3 : 1 randomization ratio of drug to placebo. The escalating doses included 25mg, lOOmg, 300mg, 600mg, and 1200mg administered intravenously (FIG. 7, panel A). Serum was collected over a span of 42 days. The resulting SAD PK data indicated a mAb5 circulating serum concentration of greater than or equal to 10 pg / mL at 28 days reached at doses of 300 mg fixed dose or above.

[0552] The MAD study consisted of 2 cohorts with 8 subjects per cohort at a 3 : 1 randomization ratio of drug to placebo. Two administrations of mAb5 per subject occurred on day 1 and 15 with a dose of either 600mg or 1200mg intravenously (FIG. 7, panel B). Serum was collected over a span of 42 days. The resulting MAD PK data indicated a mAb5 half-life of about 11 days at the 1200mg dose.

[0553] Serum from the SAD and MAD studies were used in a flow cytometry -based assay to measure the functional activity of mAb5 in whole blood. Hyper IL-11 was used to stimulate whole blood samples obtained from patients before and after dosing with mAb5. Hyper IL-11 is a covalently linked complex of IL-11 and soluble IL-11R that binds and signals through cell surface-associated glycoprotein 130 (Dams-Kozlowska et al. BMC Biotechnol. 12:8 (2012)). Addition of hyper IL-11 to whole blood leads to robust phosphorylation of STAT3 and is measurable by flow cytometry in both the CD3+ T-cell and CD14+ monocyte populations. The presence of mAb5 in whole blood inhibited the ability of hyper IL-11 to phosphorylate STAT3 in a dose dependent manner. (FIGS. 8-9).

[0554] Further analyses were conducted to determine if PK / PD relationships could be elucidated. The near immediacy with which pSTAT3 activity fell after dose administration, coupled with the rapid rebound in activity over time at lower doses, suggested a directional relationship between mAb5 serum concentration and pSTAT3 activity. There was a high degree of correlation between time matched hyper IL-11 induced pSTAT3 activity in monocytes and drug concentration (FIG. 10). The relationship follows a traditional, sigmoid Emax relationship where there is very little effect at the lowest concentrations (ie, <0.3 pg / mL), a rapid decline in pSTAT3 activity associated with concentrations ranging from 0.3 to ~1.0 pg / mL, and a complete inhibition of pSTAT activity at concentrations >1.0 pg / mL. This data shows saturation of pSTAT3 signaling at approximately 1 pg / mL correlating with the predicted therapeutic dose of 300 mg.

[0555] Adverse effects in both the SAD and MAD cohorts were monitored, and treatment emergent adverse events (TEAEs) are reported in FIG. 11. All adverse effects were mild or moderate, with the most frequent adverse effect being headache with a total of 13 instances. No dose relatedness was seen in association of headaches. The data herein is blinded and includes subjects on placebo.

[0556] Additional studies have been initiated with planned multiple doses of 1200 mg in patients with IPF and PF-ILD (Part C) and TED (Part D) as indicated by the study plan schematic in FIG. 6.Example 3: IPF Dosing

[0557] The expected doses of mAb5 in Part A, including the starting dose of 25 mg, were based on safety and pharmacology results from nonclinical studies, PK / PD modeling, safety margins, and translational experiments. The projected safety margins for the highest proposeddose in Part A (1200 mg) were 9.6-fold for AUCo-14d and 8.9-fold for Cmax, based on the no- observed-adverse-effect level (NOAEL) identified in cynomolgus monkeys.

[0558] Safety data was reviewed after parts A and B were completed. As there were no events associated with higher doses of mAb5, nor any serious or severe events were reported in parts A and B, the highest dose was tested in parts C and D in IPF and TED patients. Therefore, dosing patients with IPF / PF-ILD and TED at 1200 mg dose was justified.

[0559] From an efficacy point of view, cell line and PK data were used to project the minimum concentration needed for potential efficacy paired with target engagement data.

[0560] In support of projection of dose in IPF, data from two separate precision cut lung slice studies (PCLS) showed statistically significant attenuation of relevant fibrotic markers at varying concentrations of mAb5 ranging from 0.3-3 pg / mL. FIG. 12 shows a mAb5 induced reduction of the fibrotic markers, collagen I, fibronection and TIMP I in human IPF precision cut lung slices (PCLS). PCLS were prepared from biopsy confirmed, explanted IPF human lung tissue collected at the time of lung transplantation. These are data from n=6 replicates from a single donor that were treated with mAb5 at concentration of 0.3 pg / mL = 2 nM; 3 pg / mL = 20 nM, 30 pg / mL = 200 nM.

[0561] Assuming a conservative effective tissue concentration of 1 pg / mL based on these PCLS studies and an antibody biodistribution of plasma to lung tissue of 15%, the required plasma concentration of mAb5 is estimated to be around 6.7 pg / mL, supporting a 300mg monthly dose (see Shah DK, Betts AM. Antibody biodistribution coefficients: inferring tissue concentrations of monoclonal antibodies based on the plasma concentrations in several preclinical species and human. MAbs. 2013 Mar-Apr;5(2):297-305.).

[0562] Similarly, ex vivo studies using orbital fibroblasts from TED patients demonstrated that a mAb5 concentration of 1 pg / mL produced robust reductions in HA formation. FIG. 13 shows the effects of mAb5 on collagen production by hydroxyproline in a humanized mouse model of IPF involving adoptive transfer of mixed IPF lung cells into immunodeficient mice. Previous studies have shown that this model can recapitulate many of the hallmark pathological features of IPF, thereby providing a good translational model to assess mAb5 efficacy as a treatment for IPF (see Habiel DM, Espindola MS, Jones IC, Coelho AL, Stripp B, Hogaboam CM. CCR10+ epithelial cells from idiopathic pulmonary fibrosis lungs drive remodeling. JCI Insight. 2018 Aug 23;3(16):el22211. and Habiel DM, Espindola MS, Coelho AL, Hogaboam CM. Modeling Idiopathic Pulmonary Fibrosis in Humanized Severe Combined Immunodeficient Mice . Am J Pathol. 2018 Apr;188(4):891-903). Significant lung efficacy was observed in this humanized mouse model at dose of 1 mg / kg, administeredtwice weekly (BIW). Cmin plasma concentration at the 1 mg / kg dose was 6.3 pg / mL, indicating plasma concentrations at or above this level can provide sufficient target engagement to achieve full efficacy of mAb5 on human IPF cells. * denotes p<0.05 versus isotype control by One Way ANOVA with Tukey’s post-hoc multiple comparisons test.

[0563] The 300 mg dose and higher are projected to exceed the 1 pg / mL threshold in orbital tissues. As distribution of antibodies from blood to orbital fibroblast is not well reported in literature, applying a conservative serum -to-eye partitioning factor of approximately 10%, a serum concentration of approximately 10 pg / mL is also predicted to achieve effective levels in the eye.Example 4: SC Dosing

[0564] Pharmacokinetic (PK) simulations were performed to determine subcutaneous (SC) dosing regimens that provide comparable exposure to a reference intravenous (IV) dosing regimen of mAb5 (FIGS. 14A-14G). The reference IV regimens include both 300mg and 600mg doses administered once every four weeks (Q4W).

[0565] SC regimens tested across various dosing intervals (Q2W, Q3W) and bioavailability assumptions demonstrated that SC doses of 300 mg and 600 mg could provide Cmin values and percent target coverage comparable to those achieved with IV dosing. Based on these results and constraints around acceptable injection volumes (2.0 mL upper limit for standard SC administration) and number of injections (1-4 standard SC injections), SC dose levels up to 1200 mg (e.g. four 2 mL injections of 300 mg each) were projected to be pharmaceutically feasible.

Claims

CLAIMS1. A method of treating idiopathic pulmonary fibrosis (IPF) in a human subject in need thereof, comprising administering to the subject one or more dose(s) of about 300 mg to about 1200 mg per dose of an antibody which binds to human interleukin- 11 receptor subunit a (IL- 1 IRa).

2. The method of claim 1, wherein the IL-1 IRa antibody comprises a heavy chain complementarity determining region (HCDR) 1, HCDR2, and HCDR3, and a light chain complementarity determining region (LCDR) 1, LCDR2, and LCDR3, wherein: a. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; b. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively; c. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; d. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively; e. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; f. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively; g. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 14, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; h. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 15, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;i. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 16, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; j. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 17, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; k. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 18, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; l. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and19, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; m. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and20, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; n. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 21, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; o. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 22, respectively; p. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 23, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; q. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 24, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; r. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 25, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; s. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 26, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;t. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 27, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; u. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 28, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; v. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 29, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; w. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 30, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; x. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 31, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; y. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 32, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; z. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 33, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; aa. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 34, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; bb. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 35, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; cc. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 36, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; dd. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 37, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;ee. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 38, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; or ff. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 39, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 40, 9, and 10, respectively.

3. The method of claim 1 or 2, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein: a. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; b. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; c. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; d. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; e. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; f. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; g. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 46, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; h. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 47, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; i. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 48, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; j . the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 49, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; k. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 50, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; l. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 51, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; m. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; n. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;o. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 54, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; p. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; q. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 56, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; r. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 57, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; s. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 58, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; t. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 59, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; u. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 60, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; v. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 61, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; w. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 62, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; x. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; y. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 64, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; z. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 65, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; aa. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 66, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; bb. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; cc. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;dd. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; ee. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or ff the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.

4. The method of any one of claims 1-2, wherein the IL-1 IRa antibody is a full-length antibody.

5. The method of any one of claims 1-2, wherein the IL-1 IRa antibody is an antibody fragment.

6. The method of any one of claims 1-5, wherein the IL-1 IRa antibody comprises an Fc domain.

7. The method of claim 6, wherein the Fc domain is selected form the group consisting of human IgGl, IgG2, IgG3, and IgG4 heavy chain sequence.

8. The method of claim 7, wherein the Fc domain comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.

9. The method any one of claims 6-8, wherein the Fc domain comprises one or more amino acid substitutions.

10. The method of claim 9, wherein the one or more amino acid substitutions comprises a S228P substitution, wherein the position number of the amino acid residue is of the EU numbering scheme.

11. The method of claim 9 or 10, wherein the one or more amino acid substitutions extend the IL-1 IRa antibody’s half-life.

12. The method of any one of claims 9-11, wherein the one or more amino acid substitutions are selected from the group consisting of M252Y, S254T, and T256E substitutions, wherein the position numbers of the amino acid residues are of the EU numbering scheme.

13. The method of any one of claims 9-12, wherein the one or more amino acid substitutions are selected from the group consisting of M428L and N434S substitutions, wherein the position numbers of the amino acid residues are of the EU numbering scheme.

14. The method of claim 9, wherein the one or more amino acid substitutions are selected from the group consisting of L234A, L235A, and P329S substitutions, wherein the position numbers of the amino acid residues are of the EU numbering scheme.

15. The method of any one of claims 1-14, wherein the antibody comprises a heavy chain (HC) and a light chain (LC), wherein: a. the HC of the antibody comprises the amino acid sequence of SEQ ID NO: 72, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;b. the HC of the antibody comprises the amino acid sequence of SEQ ID NO: 74, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; c. the HC of the antibody comprises the amino acid sequence of SEQ ID NO: 87, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; d. the HC of the antibody comprises the amino acid sequence of SEQ ID NO: 88, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or e. the HC of the antibody comprises the amino acid sequence of SEQ ID NO: 89, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the LC of the antibody comprises the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.

16. The method of any one of claims 1-15, wherein the antibody wherein the antibody comprises a heavy chain (HC) and a light chain (LC), wherein: a. the HC of the antibody is encoded by the nucleic acid sequence of SEQ ID NO: 78 or an nucleic acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the LC of the antibody is encoded by the nucleic acid sequence of SEQ ID NO: 79, or an nucleic acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or b. the HC of the antibody is encoded by the nucleic acid sequence of SEQ ID NO: 80 or an nucleic acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; and wherein the LC of the antibody is encoded by the nucleic acid sequence of SEQ ID NO: 79, or an nucleic acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.

17. The method of any one of claims 1-16, wherein the dose is administered daily, weekly, about every two weeks, about every three weeks, about every four weeks, every month, or every two months.

18. The method of any one of claims 1-17, wherein the dose is administered intravenously.

19. The method of any one of claims 1-17, wherein the dose is administered subcutaneously.

20. The method of any one of claims 1-19, wherein the dose is achieved by at least 2 to about 5 administrations.

21. The method of any one of claims 1-19, wherein the dose is administered at a volume of about 1 mL, about 2 mL, about 3 mL or about 4 mL.

22. The method of any one of claims 1-19, wherein the dose is administered at a volume of about 1 mL to about 25 mL.

23. The method of any one of claims 1-13, wherein a dose of about 1200 mg is administered intravenously to the subject at a volume of about 60 mL about every four weeks.

24. The method of any one of claims 1-23, wherein the dissociation constant (KD) of the IL- 1 IRa antibody to human IL-1 IRa is less than about 50 pM.

25. The method of any one of claims 1-24, wherein the IL-1 IRa antibody does not bind to mouse IL-1 IRa or rat IL-1 IRa.

26. The method of any one of claims 1-25, wherein the IL-1 IRa antibody inhibits IL-11 induced phosphorylation of STAT3.

27. The method of any one of claims 1-26, wherein the IL-1 IRa antibody inhibits IL-11 induced phosphorylation of ERK.

28. The method of any one of claims 1-27, wherein the IL-1 IRa antibody inhibits procollagen release.

29. The method of any one of claims 1-28, wherein an additional IPF therapy is administered during a course of treatment with the IL- 1 IRa antibody.

30. The method of claim 29, wherein the additional IPF therapy is administered concurrently with the administration of the IL- 1 IRa antibody.

31. The method of claim 29, wherein the additional IPF therapy is administered after the administration of the IL- 1 IRa antibody.

32. The method of claim 29, wherein the additional IPF therapy is administered prior to the administration of the IL- 1 IRa antibody.

33. The method of any one of claims 29-32, wherein the additional IPF therapy is selected from the group consisting of an anti-fibrotic, Pirfenidone, Nintedanib, PDE4 inhibitor (e.g., Nerandomilast (BI 1015550)), an Integrin inhibitor (e.g., Bexotegrast (PLN- 74809)), and a hedgehog inhibitor (e.g., ENV-101 (taladegib)).

34. The method of any one of claims 29-33, wherein the at least one additional IPF therapy is administered intravenously, subcutaneously, intramuscularly, topically, orally, transdermally, intraperitoneally, intraorbitally, intrathecally, intraventricularly, intranasally, transmucosally, through implantation, through inhalation, or through an on- body device or infuser.

35. A bispecific antibody comprising:a. a first antigen binding arm that specifically binds to IL-1 IRa, comprising a heavy chain complementarity determining region (HCDR) 1, HCDR2, and HCDR3, and a light chain complementarity determining region (LCDR) 1, LCDR2, and LCDR3, wherein: i. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; ii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively; iii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; iv. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively; v. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; vi. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively; vii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 14, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; viii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 15, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; ix. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 16, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;x. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5,17, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xi. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5,18, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 19, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xiii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 20, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xiv. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 21, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xv. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 22, respectively; xvi. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 23, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xvii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 24, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xviii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 25, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xix. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 26, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xx. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 27, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;xxi. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 28, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 29, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxiii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 30, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxiv. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 31, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxv. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 32, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxvi. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 33, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxvii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 34, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxviii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 35, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxix. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 36, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxx. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 37, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxxi. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 38, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; orxxxii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 39, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 40, 9, and 10, respectively; and b. a second antigen binding arm that specifically binds to an IPF associated antigen.

36. The bispecific antibody of claim 35, wherein the first antigen binding arm comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein: a. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; b. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; c. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;d. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; e. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; f. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; g. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 46, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; h. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 47, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; i. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 48, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; j . the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 49, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; k. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 50, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; l. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 51, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; m. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; n. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; o. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 54, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; p. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; q. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 56, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; r. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 57, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;s. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 58, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; t. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 59, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; u. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 60, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; v. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 61, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; w. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 62, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; x. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; y. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 64, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; z. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 65, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; aa. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 66, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; bb. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; cc. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; dd. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; ee. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or ff the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.

37. The bispecific antibody of claim 35 or 36, wherein the IPF associated antigen is selected from the group consisting of a receptor tyrosine kinase (RTK) such as vascular endothelial growth factor (VEGF), fibroblast growth factor receptor (FGFR), and Platelet- derived growth factor receptor (PDGFR), PDE4, integrin, hedgehog, and connective tissue growth factor (CTGF).

38. The bispecific antibody of any one of claims 35-37, wherein the second antigen binding arm comprises a VH and a VL sequence derived from pamrevlumab.

39. An antibody-drug conjugate (ADC) comprising:a. an antibody that specifically binds to IL-1 IRa, wherein the antibody comprising a heavy chain complementarity determining region (HCDR) 1, HCDR2, and HCDR3, and a light chain complementarity determining region (LCDR) 1, LCDR2, and LCDR3, wherein: i. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; ii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 6, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively; iii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; iv. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 7, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively; v. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; vi. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 11, respectively; vii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 14, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; viii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 15, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; ix. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 16, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;x. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5,17, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xi. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5,18, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 19, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xiii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 20, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xiv. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 21, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xv. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 5, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 22, respectively; xvi. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 23, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xvii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 24, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xviii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 25, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xix. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 26, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xx. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 27, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively;xxi. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 28, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 29, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxiii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 30, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxiv. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 31, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxv. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 32, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxvi. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 33, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxvii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 34, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxviii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 35, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxix. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 36, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxx. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 37, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; xxxi. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 38, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 8, 9, and 10, respectively; orxxxii. the HCDR1, HCDR2, and HCDR3 sequences comprise SEQ ID NOs: 39, 12, and 13, respectively, and the LCDR1, LCDR2, and LCDR3 sequences comprise SEQ ID NOs: 40, 9, and 10, respectively; b. a linker; and c. an IPF therapeutic drug.

40. The ADC of claim 39, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein: a. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; b. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 41, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; c. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; d. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; e. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; f. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:43, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; g. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 46, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; h. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 47, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; i. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 48, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; j . the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 49, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; k. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 50, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; l. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 51, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; m. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 52, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; n. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;o. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 45, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 54, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; p. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 55, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; q. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 56, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; r. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 57, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; s. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 58, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; t. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 59, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; u. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 60, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; v. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 61, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; w. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 62, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; x. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 63, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; y. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 64, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; z. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 65, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; aa. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 66, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; bb. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 67, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; cc. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 68, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto;dd. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 69, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; ee. the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 70, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto; or ff the VH of the antibody comprises the amino acid sequence of SEQ ID NO: 71, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto, and the VL of the antibody comprises the amino acid sequence of SEQ ID NO: 42, or an amino acid sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto.

41. The ADC of claim 39 or 40, wherein the IPF therapeutic drug is selected from the group consisting of an anti-fibrotic, Pirfenidone, Nintedanib, a PDE4 inhibitor, such as Nerandomilast (BI 1015550), a PI3K / mTOR inhibitor (e.g., Omipalisib), an Integrin inhibitor (e.g., PLN-74809), and a hedgehog inhibitor (e.g., ENV-101).

42. The ADC of any one of claims 39-41, wherein the linker is a cleavable linker.

43. Use of an antibody which binds to human interleukin-11 receptor subunit a (IL-1 IRa) in the manufacture of a medicament for treating idiopathic pulmonary fibrosis (IPF) in a human subject in need thereof, wherein the antibody is administered to the subject in one or more dose(s) of about 300 mg to about 1200 mg per dose.

44. An antibody which binds to human interleukin- 11 receptor subunit a (IL-1 IRa) for use in the treatment of idiopathic pulmonary fibrosis (IPF) in a human subject in need thereof, wherein the antibody is administered to the subject in one or more dose(s) of about 300 mg to about 1200 mg per dose.

Images