Immunomodulatory fusion proteins and related methods

Abstract

Provided herein are immunomodulatory fusion proteins and compositions (e.g., pharmaceutical compositions) comprising the same; as well as methods of making the immunomodulatory fusion proteins and compositions. The immunomodulatory fusion proteins provided herein are useful in pharmaceutical compositions and methods of use (including, e.g., methods of suppressing or reducing (e.g., preventing) a pro-inflammatory immune response in a subject).

Description

Attorney Docket No.62801.72WO01 IMMUNOMODULATORY FUSION PROTEINS AND RELATED METHODS RELATED APPLICATIONS

[0001] This application to claims priority to and the benefit of U.S. Serial No.: 63 / 671,604, filed July 15, 2024; U.S. Serial No.: 63 / 671,614, filed July 15, 2024; U.S. Serial No.: 63 / 684,935, filed August 20, 2024; U.S. Serial No.: 63 / 715,908, filed November 4, 2024; U.S. Serial No.: 63 / 715,937, filed November 4, 2024; the entire contents of each of which is incorporated herein by reference. 1. FIELD

[0002] This disclosure relates to immunomodulatory fusion proteins and nucleic acid molecules encoding the same, as well as pharmaceutical compositions comprising any of the foregoing. The disclosure further relates to methods of making and utilizing the same, including, e.g., methods of suppressing or reducing (e.g., preventing) a pro-inflammatory immune response. 2. BACKGROUND

[0003] Fusion proteins are a class of engineered proteins that comprise at least one protein operably connected to another protein, wherein the two proteins are not naturally found operably connected. Fusion proteins can be utilized for example, to add one or more functionality to a single protein. For example, fusion proteins are commonly utilized as detection reagents (e.g., florescent proteins fused to a targeting protein (e.g., an antibody that binds a specific target antigen)). Fusion proteins can also be utilized as, e.g., therapeutic, and diagnostic agents. 3. SUMMARY

[0004] Provided herein are, inter alia, immunomodulatory fusion proteins (and nucleic acid molecules encoding the same) and combinations regimens of immunomodulatory proteins (and fusion proteins thereof); methods of manufacturing the same; pharmaceutical compositions comprising the same; and methods of use including e.g., suppressing or reducing (e.g., preventing) an immune response; and methods of suppressing or reducing (e.g., preventing) a pro- inflammatory immune response.

[0005] Accordingly, provided herein are, inter alia, fusion protein comprising (a) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%,Attorney Docket No.62801.72WO01 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; and any one or more (e.g., 1, 2, 3, or 4) of (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454; (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464; (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576; and / or (a-1) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

[0006] Also, provided herein are, inter alia, fusion proteins comprising (a) an integrin binding domain; and one or more of (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454; (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464; and / or (e) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. 4. BRIEF DESCRIPTION OF THE FIGURES

[0007] FIG.1A is a graphical representation of an exemplary format of an immunomodulatory fusion protein described herein, wherein the C-terminus of a first immunomodulatory protein described herein is operably connected indirectly through a peptide linker to the N-terminus of an Ig (e.g., hIg) Fc region, and the N-terminus of a second immunomodulatory protein described herein is operably connected indirectly through a peptide linker to the C-terminus of the Ig (e.g.,Attorney Docket No.62801.72WO01 hIg) Fc region.

[0008] FIG.1B is a graphical representation of an exemplary format of an immunomodulatory fusion protein described herein, wherein the N-terminus of a first immunomodulatory protein described herein is operably connected indirectly through a peptide linker to the C-terminus a full- length antibody, and the N-terminus of a second immunomodulatory protein described herein is operably connected indirectly through a peptide linker to the C-terminus of the first immunomodulatory protein.

[0009] FIG. 2 is a line graph showing the % of IL-10 activity in cell cultures treated with the indicated agent (IFP-1, Fc-control, or a control IL-10 binder (hIL-10 control)) at the indicated concentration.

[0010] FIG.3 is a is a line graph showing the % of TNFα activity in cell cultures treated with the indicated agent (IFP-1, Fc-control, or a control TNFα binder (TNFα control)) at the indicated concentration.

[0011] FIG. 4 is a line graph showing the % of IL-10 activity in cell cultures treated with the indicated agent (IFP-2, Fc-control, or a control IL-10 binder (IL-10 control)) at the indicted concentration.

[0012] FIG.5 is a is a line graph showing the % of TNFα activity in cell cultures treated with the indicated agent (IFP-10, a control TNFα binder (TNFα control), a control TL1A binder (TL1A control)) at the indicated concentration.

[0013] FIG.6 is a is a line graph showing the NFκB activity (as a measure of TL1A inhibition) in cell cultures treated with the indicated agent (IFP-10, a control TNFα binder (TNFα control), or a control TL1A binder (TL1A control)) at the indicated concentration.

[0014] FIG.7A is a graphical representation of an exemplary format of an immunomodulatory fusion protein described herein, wherein the N-terminus of a first immunomodulatory protein described herein is indirectly operably connected to the C-terminus of one of the heavy chains a full-length anti-integrin (e.g., α4β7 integrin) antibody through a peptide linker, and the N-terminus of a second immunomodulatory protein described herein is indirectly operably connected to the C-terminus of the other the heavy chain of the full-length anti-integrin (e.g., α4β7 integrin) antibody through a peptide linker. In some embodiments, the first and second immunomodulatory proteins have an identical amino acid sequence.

[0015] FIG.7B is a graphical representation of an exemplary format of an immunomodulatoryAttorney Docket No.62801.72WO01 fusion protein described herein, wherein the N-terminus of a first immunomodulatory protein described herein is indirectly operably connected to the C-terminus of one of the heavy chains a full-length anti-integrin (e.g., α4β7 integrin) antibody through a peptide linker; the N-terminus of a second immunomodulatory protein described herein is indirectly operably connected to the C- terminus of the first immunomodulatory protein through a peptide linker; the N-terminus of a third immunomodulatory protein described herein is indirectly operably connected to the C-terminus of the other heavy chain of the full-length anti-integrin (e.g., α4β7 integrin) antibody through a peptide linker; and the N-terminus of a fourth immunomodulatory protein described herein is indirectly operably connected through a peptide linker to the C-terminus of the third immunomodulatory protein through a peptide linker. In some embodiments, the first and third immunomodulatory proteins have an identical amino acid sequence; and the second and fourth immunomodulatory proteins have an identical amino acid sequence.

[0016] FIG.7C is a graphical representation of an exemplary format of an immunomodulatory fusion protein described herein, wherein the N-terminus of an Ig Fc region is indirectly operably connected to the C-terminus of an anti-integrin (e.g., α4β7 integrin) scFv through a peptide linker, and the N-terminus of an immunomodulatory protein is indirectly operably connected to the C- terminus of the Ig Fc region through a peptide linker.

[0017] FIG.8 is a line graph showing the relative inhibition of the binding of integrin α4β7 to MAdCAM-1 in cell cultures treated with the indicated agent (IFP-13, IFP-14, or anti-integrin α4β7 antibody (positive control)) at the indicated concentration.

[0018] FIG.9 is a is a line graph showing the % of TNFα activity in cell cultures treated with the indicated agent (IFP-13, IFP-14, or anti-integrin α4β7 antibody (positive control)) at the indicated concentration.

[0019] FIG. 10 is a is a line graph showing the NFκB activity (as a measure of TL1A inhibition) in cell cultures treated with the indicated agent (IFP-13, IFP-14, or anti-integrin α4β7 antibody (positive control)) at the indicated concentration.

[0020] FIG. 11 is a line graph showing the relative inhibition of the binding of integrin α4β7 to MAdCAM-1 in cell cultures treated with the indicated agent (IFP-12, negative control) at the indicated concentration.

[0021] FIG.12 is a is a line graph showing the % of TNFα activity in cell cultures treated with the indicated agent (IFP-12, TNF Binder (positive control)) at the indicated concentration.Attorney Docket No.62801.72WO01

[0022] FIG. 13 is a line graph showing the relative inhibition of the binding of integrin α4β7 to MAdCAM-1 in cell cultures treated with the indicated agent (IFP-13, IFP-14, IFP-16, or anti- integrin α4β7 antibody (positive control)) at the indicated concentration.

[0023] FIG.14 is a is a line graph showing the % of TNFα activity in cell cultures treated with the indicated agent (IFP-13, IFP-14, IFP-16, or anti-integrin α4β7 antibody (positive control)) at the indicated concentration.

[0024] FIG. 15 is a is a line graph showing the NFκB activity (as a measure of TL1A inhibition) in cell cultures treated with the indicated agent (IFP-13, IFP-14, IFP-16, or anti-integrin α4β7 antibody (positive control)) at the indicated concentration. 5. DETAILED DESCRIPTION

[0025] The inventors have, inter alia, developed immunomodulatory fusion proteins that, e.g., are capable of simultaneously binding and / or functionally targeting multiple proteins and / or signaling pathways. Accordingly, the novel immunomodulatory fusion proteins disclosed herein may be useful for various methods, including, e.g., selectively inhibiting or reducing (e.g., preventing) binding of a plurality of cognate receptor / ligand pairs, inhibiting or reducing (e.g., preventing) signaling mediated through the binding of such cognate receptor / ligand pairs, and modulating (e.g., suppressing or reducing (e.g., preventing)) an immune response. As such, the current disclosure provides, inter alia, novel immunomodulatory fusion proteins, nucleic acid molecules encoding the same, and pharmaceutical compositions comprising any of the foregoing, along with the methods for utilizing the same. TABLE OF CONTENTS 5.1 Definitions 5.2 Immunomodulatory Proteins and Fusion Proteins Thereof 5.2.1 Combinatorial Immunomodulatory Proteins 5.2.1.1 IL-10R Binding Proteins 5.2.1.1(i) Exemplary Properties of IL-10R Binding Proteins 5.2.1.2 TL1A Binding Proteins 5.2.1.2(i) Exemplary Properties of TL1A Binding Proteins 5.2.1.3 TNFα Binding ProteinsAttorney Docket No.62801.72WO01 Exemplary Properties of TNFα Binding Proteins CD30 Ligand Binding Proteins Exemplary Properties of CD30L Binding Proteins Integrin Targeting Immunomodulatory Fusion Proteins Integrin Binding Domains IL10-R Binding Proteins, TL1A Binding Proteins, TNFα Binding Proteins, and CD30L Binding Proteins Half-Life Extension Moieties Ig Fusion Proteins Antibody Fusion Proteins Ig Constant Region (e.g., Ig Fc) Fusion Proteins Half-Life Extension Ig Fc Effector Function Reduced Ig Fc Effector Function Enhanced Ig Effector Function Signal Peptides Components & Formats Exemplary Combinations of Immunomodulatory Protein Components Exemplary Formats Multimeric Fusion Proteins Exemplary Immunomodulatory Fusion Proteins Exemplary Properties of Immunomodulatory Fusion Proteins Conjugates & Additional Fusion Proteins Radioligands Chimeric Antigen Receptors Methods of Making Proteins Nucleic Acid Molecules DNA Molecules RNA Molecules Vectors Non-Viral VectorsAttorney Docket No.62801.72WO01 Viral Vectors Cells Carriers Carriers of Immunomodulatory Fusion Proteins Carriers Conjugated to Immunomodulatory Fusion Proteins Lipid Based Carriers / Lipid Nanoformulations Cationic Lipids (Positively Charged) and Ionizable Lipids Non-Cationic Lipids (e.g., Phospholipids) Structural Lipids Polymers and Polyethylene Glycol (PEG) - Lipids Percentages of Lipid Nanoformulation Components Pharmaceutical Compositions Combination Regimens Combination Compositions Methods of Use Methods of Inhibiting or Reducing (e.g., Preventing) Receptor-Ligand Interactions Methods of Inhibiting or Reducing (e.g., Preventing) Binding of a Plurality of Respective Receptor Ligand Interactions Methods of Inhibiting or Reducing (e.g., Preventing) Signaling Mediated by a Receptor Ligand Interaction Methods of Inhibiting or Reducing (e.g., Preventing) Signaling Mediated by a Plurality of Respective Receptor Ligand Interactions Methods of Suppressing or Reducing (e.g., Preventing) a Pro-Inflammatory Immune Response Methods of Preventing, Treating, or Ameliorating a Disease in a Subject in Need Thereof Kits ionsAttorney Docket No.62801.72WO01

[0026] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0027] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the claimed subject matter belongs. It is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of any subject matter claimed.

[0028] Use of the singular herein includes the plural unless specifically stated otherwise. For example, as used herein, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Furthermore, use of the term “including” as well as other forms, such as “include,” “includes,” and “included,” is not limiting.

[0029] It is understood that wherever aspects are described herein with the language “comprising,” otherwise analogous aspects described in terms of “consisting of” and “consisting essentially of” are also provided.

[0030] The term “and / or” where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. Thus, the term “and / or” as used in a phrase such as “A and / or B” herein is intended to include “A and B,” “A or B,” “A” (alone), and “B” (alone). Likewise, the term “and / or” as used in a phrase such as “A, B, and / or C” is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0031] As described herein, any concentration range, percentage range, ratio range or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and one hundredth of an integer), unless otherwise indicated.

[0032] The term “about” refers to a value or composition that is within an acceptable error range for the particular value or composition as determined by one of ordinary skill in the art, which will depend in part on how the value or composition is measured or determined, i.e., the limitations of the measurement system. When particular values or compositions are provided herein, unless otherwise stated, the meaning of “about” should be assumed to be within an acceptable error range for that particular value or composition.

[0033] Where proteins and / or polypeptides are described herein, it is understood that nucleicAttorney Docket No.62801.72WO01 acid molecules (e.g., RNA (e.g., mRNA) or DNA molecules) encoding the protein are also provided herein.

[0034] Where proteins, peptides, nucleic acid molecules, vectors, carriers, etc. are described herein, it is understood that isolated forms of the proteins, peptides, nucleic acid molecules, vectors, carriers, etc. are also provided herein.

[0035] Where proteins, peptides, nucleic acid molecules, etc. are described herein, it is understood that recombinant forms of the proteins, peptides, nucleic acid molecules, etc. are also provided herein.

[0036] Where polypeptides or sets of polypeptides are described herein, it is understood that proteins comprising the polypeptides or sets of polypeptides folded into their three-dimensional structure (i.e., tertiary or quaternary structure) are also provided herein and vice versa.

[0037] As used herein, the term “adjuvant” refers to a substance that causes stimulation of the immune system of a subject when administered to the subject.

[0038] As used herein, the term “administering” refers to the physical introduction of an agent, e.g., a therapeutic agent (or a precursor of the therapeutic agent that is metabolized or altered within the body of the subject to produce the therapeutic agent in vivo) or vaccine to a subject, using any of the various methods and delivery systems known to those skilled in the art. Administering can also be performed, for example, once, a plurality of times, and / or over one or more extended periods. The term administering includes both self-administration by the subject themselves and administration to the subject by another.

[0039] As used herein, the term “affinity” refers to the strength of the binding of one protein (e.g., a Ligand) to another protein (e.g., a Receptor). The affinity of a protein is measured by the dissociation constant Kd, defined as [Ligand] x [Receptor] / [Ligand-Receptor] where [Ligand- Receptor] is the molar concentration of the Ligand-Receptor complex, [Ligand] is the molar concentration of the unbound Ligand and [Receptor] is the molar concentration of the unbound Receptor. The affinity constant Ka is defined by 1 / Kd. Standard methods of measuring affinity are known to the person of ordinary skill in the art and described herein, see, e.g., § 5.9.

[0040] As used herein, the term “agent” is used generically to describe any macro or micro molecule. Exemplary agents include, but are not limited proteins, peptides, nucleic acid molecules (e.g., DNA molecules, RNA molecules), vectors, carriers, carbohydrates, lipids, synthetic polymers, etc.Attorney Docket No.62801.72WO01

[0041] As used herein, the term “antibody” or “antibodies” is used in the broadest sense and encompasses various immunoglobulin (Ig) (e.g., human Ig (hIg), murine Ig (mIg)) structures, including, but not limited to monoclonal antibodies, polyclonal antibodies, multispecific (e.g., bispecific, trispecific) antibodies, and antibody fragments so long as they exhibit the desired antigen-binding activity (i.e., antigen binding fragments or variants). The term antibody thus includes, for example, full-length antibodies; antigen-binding fragments of full-length antibodies; molecules comprising antibody CDRs, VH regions, and / or VL regions; and antibody-like scaffolds (e.g., fibronectins). Examples of antibodies include, without limitation, monoclonal antibodies, polyclonal antibodies, monospecific antibodies, multispecific antibodies, human antibodies, humanized antibodies, chimeric antibodies, camelized antibodies, intrabodies, affybodies, diabodies, tribodies, heteroconjugate antibodies, antibody-drug conjugates, single domain antibodies (e.g.,VHH, (VHH)2), single chain antibodies, single-chain Fvs (scFv; (scFv)2), Fab fragments (e.g., Fab, single chain Fab (scFab), F(ab’)2 fragments, disulfide-linked Fvs (sdFv), Fc fusions (e.g., Fab-Fc, scFv-Fc, VHH-Fc, (scFv)2-Fc, (VHH)2-Fc), and antigen-binding fragments of any of the above, and conjugates or fusion proteins comprising any of the above. Antibodies can be of Ig isotype (e.g., IgG, IgE, IgM, IgD, or IgA), any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1or IgA2), or any subclass (e.g., IgG2aor IgG2b) of Ig). In certain embodiments, antibodies described herein are IgG antibodies, or a class (e.g., human IgG1 or IgG4) or subclass thereof. In certain embodiments, antibodies described herein are mIgG antibodies, or a class (e.g., mIgG1 or mIgG2a) or subclass thereof. In some embodiments, the antibody is a human, humanized, or chimeric IgG1or IgG4monoclonal antibody. In some embodiments, the term antibodies refers to a monoclonal or polyclonal antibody population. Antibodies described herein can be produced by any standard methods known in the art, e.g., recombinant production in host cells, see, e.g., § 5.11; or synthetic production.

[0042] As used herein, the term “antibody mimetic” refers to non-Ig based antigen binding domain. Various antibody-like scaffolds are known in the art. For example, 10th type III domain of fibronectin (e.g., AdNectins®) and designed ankyrin repeat proteins (e.g., DARPins®) have been used as alternative scaffolds for antigen-binding domains, see, e.g., Gebauer and Skerra, Engineered protein scaffolds as next-generation antibody therapeutics. Curr Opin Chem Biol 13:245-255 (2009) and Stumpp et al., Darpins: A new generation of protein therapeutics. Drug Discovery Today 13: 695-701 (2008), the full contents of each of which is incorporated byAttorney Docket No.62801.72WO01 reference herein for all purposes. Exemplary antibody-like scaffolds include, but are not limited to, lipocalins (see, e.g., US7250297) (e.g., Anticalin®), protein A-derived molecules such as z- domains of protein a (see, e.g., US5831012) (e.g., Affibody®), A domains of membrane receptors stabilized by disulfide bonds and Ca2+ (see, e.g., US7803907) (e.g., Avimer / Maxibody®), a serum transferrin (see, e.g., US2004023334) (e.g., Transbody®); a designed ankyrin repeat protein (see, e.g., US7417130) (e.g., DARPin®), a fibronectin (see, e.g., US6818418) (e.g., AdNectin®), a C- type lectin domain (see, e.g., US2004132094) (e.g., Tetranectin®); a human gamma-crystallin or ubiquitin (see, e.g., US7838629) (e.g., Affilin®); a kunitz type domain of human protease inhibitors (see, e.g., US2004209243), C-Type Lectins (see, e.g., US2004132094) (e.g., Tetranectins®), cysteine knots or knottins (see, e.g., US7186524) (e.g., Microbodies®), nucleic acid aptamers (see, e.g., US5475096), thioredoxin A scaffold (see, e.g., US6004746) (peptide aptamers), and 10th type III domain of fibronectin (see, e.g., US6818418) (e.g., AdNectins®), and cystine-dense peptides (see, e.g., WO2023023031). Additional exemplary antibody-like scaffolds are known in the art and for example described in Storz U. Intellectual property protection: strategies for antibody inventions. MAbs. 2011;3(3):310-317. doi:10.4161 / mabs.3.3.15530. The entire contents of each of the foregoing references is incorporated herein by reference for all purposes. Antibody like scaffolds include e.g., naturally occurring antigen binders, variant (e.g., functional variants) of naturally occurring antigen binders, fragments (e.g., functional fragments) of naturally occurring antigen binders, and synthetic antigen binders (i.e., not naturally occurring antigen binders).

[0043] As used herein the term “CD30L” or “CD30 ligand” refers to the type II transmembrane protein of the TNFSF. The amino acid sequence of an exemplary reference membrane human CD30L (hCD30L) protein is set forth in SEQ ID NO: 31.

[0044] As used herein the term “CD30” refers to the type I transmembrane receptor of the TNFSF that binds CD30L. The amino acid sequence of an exemplary reference immature human CD30 (hCD30) protein is set forth in SEQ ID NO: 32 and the amino acid sequence of an exemplary reference mature hCD30 protein is set forth in SEQ ID NO: 32.

[0045] The terms “CH1” and “CH1 region” are used interchangeably herein and refer to the first constant region of an immunoglobulin heavy chain. The amino acid sequence of an exemplary reference hIgG1 CH1 region is set forth in SEQ ID NO: 632; and the amino acid sequence of an exemplary reference hIgG4 CH1 region is set forth in SEQ ID NO: 647.Attorney Docket No.62801.72WO01

[0046] The terms “CH2” and “CH2 region” are used interchangeably herein and refer to the second constant region of an immunoglobulin heavy chain. The amino acid sequence of an exemplary reference hIgG1 CH2 region is set forth in SEQ ID NO: 634; and the amino acid sequence of an exemplary reference hIgG4 CH2 region is set forth in SEQ ID NO: 650.

[0047] The terms “CH3” and “CH3 region” are used interchangeably herein and refer to the third constant region of an immunoglobulin heavy chain. The amino acid sequence of an exemplary reference hIgG1 CH3 region is set forth in SEQ ID NO: 635; and the amino acid sequence of an exemplary reference hIgG4 CH3 region is set forth in SEQ ID NO: 651.

[0048] As used herein, the term “circular RNA” refers to a translatable RNA molecule that forms a circular structure through covalent or non-covalent bonds. In some embodiments, the circular RNA is covalently closed.

[0049] As used herein, the term “conjugation” refers to chemical conjugation of a protein with a moiety (e.g., small molecule, polypeptide, nucleic acid molecule, carbohydrate, lipid, synthetic polymer (e.g., polymers of polyethylene glycol (PEG)), etc.). The moiety can be directly connected to the protein or indirectly connected through a linker, e.g., as described herein. Chemical conjugation methods are well known in the art, as are commercially available conjugation reagents and kits, with detailed instructions for their use readily available from the commercial suppliers.

[0050] As used herein the term “DcR3” or “Tumor Necrosis Factor Receptor Superfamily Member 6B” refers to the receptor of the TNFSF that binds, e.g., FASL, LIGHT. The amino acid sequence of an exemplary reference immature human DR3 (hDR3) protein is set forth in SEQ ID NO: 27 and the amino acid sequence of an exemplary reference mature hDR3 protein is set forth in SEQ ID NO: 28.

[0051] As used herein the term “DR3” or “Tumor Necrosis Factor Receptor Superfamily Member 25” refers to the receptor of the TNFSF that binds, e.g., TL1A. The amino acid sequence of an exemplary reference immature human DR3 (hDR3) protein is set forth in SEQ ID NO: 25 and the amino acid sequence of an exemplary reference mature hDR3 protein is set forth in SEQ ID NO: 26.

[0052] As used herein, the term “derived from,” with reference to a nucleic acid molecule refers to a nucleic acid molecule that has at least 70% sequence identity to a reference nucleic acid molecule (e.g., a naturally occurring nucleic acid molecule) or a fragment thereof. The term “derived from,” with reference to a protein refers to a protein that comprises an amino acidAttorney Docket No.62801.72WO01 sequence that has at least 70% sequence identity to the amino acid sequence of a reference protein (e.g., a naturally occurring protein). The term “derived from” as used herein does not denote any specific process or method for obtaining the nucleic acid molecule, polypeptide, or protein. For example, the nucleic acid molecule, polypeptide, or protein can be recombinantly produced or chemically synthesized.

[0053] As used herein, the term “diagnosing” or “diagnosis” refers to a determination of the presence, absence, severity, or course of treatment of a disease (e.g., an infection, e.g., a viral infection). The term “diagnosing” encompasses an initial determination as well as subsequent determinations (e.g., monitoring) after the initial determination.

[0054] As used herein, the term “disease” refers to any abnormal condition that impairs physiological function. The term is used broadly to encompass any disorder, illness, abnormality, pathology, sickness, condition, or syndrome in which physiological function is impaired, irrespective of the nature of the etiology.

[0055] The terms “DNA” and “polydeoxyribonucleotide” are used interchangeably herein and refer to macromolecules that include multiple deoxyribonucleotides that are polymerized via phosphodiester bonds. Deoxyribonucleotides are nucleotides in which the sugar is deoxyribose.

[0056] The term “effector function” when used in reference to an antibody refers to those biological activities attributable to the Fc region of an antibody, which therefore vary with the antibody isotype. Antibody effector functions include, but are not limited to, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement dependent cytotoxicity (CDC), Fc receptor binding (e.g., FcγRI, FcγRIIa, FcγRIIc, FcγRIIIa, and / or FcγRIIIb (e.g., FcγRI, FcγRIIa, and / or FcγRIIIa)), and Clq binding.

[0057] As used herein the term “FAS” or “Tumor Necrosis Factor Receptor Superfamily Member 6” refers to the receptor of the TNFSF that binds, e.g., FASL. The amino acid sequence of an exemplary reference immature human FAS (hFAS) protein is set forth in SEQ ID NO: 23 and the amino acid sequence of an exemplary reference mature hFAS protein is set forth in SEQ ID NO: 24.

[0058] As used herein the term “FASL” or “FAS Ligand” or “Tumor Necrosis Factor Ligand Superfamily Member 6” refers to the immunomodulatory cytokine of the TNFSF. The amino acid sequence of an exemplary reference membrane human FASL (hFASL) protein is set forth in SEQ ID NO: 13 and the amino acid sequence of an exemplary reference soluble hFASL protein is setAttorney Docket No.62801.72WO01 forth in SEQ ID NO: 14.

[0059] As used herein, the term “Fc region” refers to the C-terminal region of an Ig heavy chain that comprises from N- to C-terminus at least a CH2 region operably connected to a CH3 region. In some embodiments, the Fc region comprises an Ig hinge region or at least a portion of an Ig hinge region operably connected to the N-terminus of the CH2 region. In some embodiments, the Fc region is engineered relative to a reference Fc region, see, e.g., § 5.4.4. Additional examples of proteins with engineered Fc regions can be found in Saunders 2019 (K. O. Saunders, “Conceptual Approaches to Modulating Antibody Effector Functions and Circulation Half-Life,” 2019, Frontiers in Immunology, V. 10, Art. 1296, pp. 1-20, the entire contents of which is incorporated by reference herein for all purposes).

[0060] As used herein, the term “full-length antibody” refers to an antibody having a structure substantially similar to a native antibody structure. E.g., an antibody comprising (i) a first Ig light chain comprising from N- to C-terminus a light chain variable region (VL) region and a light chain constant region (CL) region; (ii) a first Ig heavy chain comprising from N- to C-terminus a heavy chain variable region (VH) region, a CH1 region, a hinge region, a CH2 region, and a CH3 region; (iii) a second Ig heavy chain comprising from N- to C-terminus a VH region, a CH1 region, a hinge region, a CH2 region, and a CH3 region; (iv) a second Ig light chain comprising from N- to C-terminus a VL region and a VH region; wherein said first light chain and said first heavy chain associate to form a first antigen binding domain; wherein said second light chain and said second heavy chain associate to form a second antigen binding domain; and wherein said first heavy chain and said second heavy chain associate to form a dimer. In some embodiments, the two heavy chains comprise a substantially identical amino acid sequence; and the two light chains comprise a substantially identical amino acid sequence. In some embodiments, the two heavy chains comprise a substantially identical amino acid sequence except for one or more amino acid modifications that promote heterodimerization of the correct heavy chains (e.g., as described herein); and the two light chains comprise a substantially identical amino acid sequence. Antibody chains may be substantially identical but not entirely identical if they differ due to post- translational modifications, such as C-terminal cleavage of lysine residues, C-terminal cleavage of glycine and lysine residues, alternative glycosylation patterns, etc.

[0061] The term “functional variant” as used herein in reference to a protein refers to a protein that comprises at least one but no more than 15%, not more than 12%, no more than 10%, no moreAttorney Docket No.62801.72WO01 than 8% amino acid variation (e.g., substitution, deletion, addition) compared to the amino acid sequence of a reference protein, wherein the protein retains at least one particular function of the reference protein. Not all functions of the reference protein (e.g., wild type) need be retained by the functional variant of the protein. In some instances, one or more functions are selectively reduced or eliminated. In some embodiments, the reference protein is a wild type protein. For example, a functional variant of a TL1A binding protein can refer to a TL1A binding protein comprising one or more amino acid substitution as compared to a reference TL1A (e.g., a wild type protein) that retains the ability to specifically bind TL1A.

[0062] The term “functional fragment” as used herein in reference to a protein refers to a fragment of a reference protein that retains at least one particular function. Not all functions of the reference protein need be retained by a functional fragment of the protein. In some instances, one or more functions are selectively reduced or eliminated. In some embodiments, the reference protein is a wild type protein. For example, a functional fragment of a TL1A binding protein can refer to a fragment of a TL1A binding protein that retains the ability to specifically bind TL1A.

[0063] As used herein, the term “fuse” and grammatical equivalents thereof refer to the operable connection of at least a first polypeptide to a second polypeptide, wherein the first and second polypeptides are not naturally found operably connected together. For example, the first and second polypeptides are derived from different proteins. The term fuse encompasses both a direct connection of the at least two polypeptides through a peptide bond, and the indirect connection through a linker (e.g., a peptide linker).

[0064] As used herein, the term “fusion protein” and grammatical equivalents thereof refers to a protein that comprises at least one polypeptide operably connected to another polypeptide, wherein the two polypeptides are not naturally found operably connected together. For example, the first and second polypeptides of the fusion protein are each derived from different proteins. The at least two polypeptides of the fusion protein can be directly operably connected through a peptide bond; or can be indirectly operably connected through a linker (e.g., a peptide linker). Therefore, for example, the term fusion polypeptide encompasses embodiments, wherein Polypeptide A is directly operably connected to Polypeptide B through a peptide bond (Polypeptide A – Polypeptide B), and embodiments, wherein Polypeptide A is operably connected to Polypeptide B through a peptide linker (Polypeptide A – peptide linker – Polypeptide B).

[0065] As used herein, the term “half-life extension moiety” refers to a moiety (e.g., smallAttorney Docket No.62801.72WO01 molecule, polypeptide, nucleic acid molecule, carbohydrate, lipid, synthetic polymer (e.g., polymers of PEG), etc.) that when conjugated or otherwise operably connected (e.g., fused) to a protein (the subject protein), increases the half-life of the subject protein in vivo when administered to a subject (e.g., a human subject). The pharmacokinetic properties of the protein can be evaluated utilizing in vivo models known in the art.

[0066] As used herein, the term “half-life extension polypeptide” or “half-life extension protein” refers to a protein that when operably connected to another protein (the subject protein), increases the half-life of the subject protein in vivo when administered to a subject (e.g., a human subject). The pharmacokinetic properties of the protein can be evaluated utilizing in vivo models known in the art.

[0067] As used herein, the term “heterologous”, when used to describe a first element in reference to a second element means that the first element and second element do not exist in nature disposed as described. For example, a polypeptide comprising a “heterologous moiety” means a polypeptide that is joined to a moiety (e.g., small molecule, polypeptide, nucleic acid molecule, carbohydrate, lipid, synthetic polymer (e.g., polymers of PEG), etc.) that is not joined to the polypeptide in nature.

[0068] As used, herein the term “heterologous signal peptide” refers to a signal peptide that is not operably connected to a subject protein in nature. For example, in reference to a polypeptide comprising a signal peptide from human IL-2 operably connected to human IL-12, the human IL- 2 signal peptide would constitute a heterologous signal peptide. The terms “signal peptide” and “signal sequence” are used interchangeably herein.

[0069] The terms “hinge” or “hinge region” are used interchangeably herein and refer to the hinge region of an immunoglobulin heavy chain. The amino acid sequence of an exemplary reference hIgG1 hinge region is set forth in SEQ ID NO: 633; and the amino acid sequence of an exemplary reference hIgG4 hinge region is set forth in SEQ ID NO: 648 or 649.

[0070] As used herein, the term “heterologous signal peptide” refers to a signal peptide that is operably connected to a subject protein in nature. For example, in reference to a polypeptide comprising a signal peptide from human IL-2 operably connected to human IL-2, the human IL-2 signal peptide would constitute a heterologous signal peptide.

[0071] As used herein, the term “in combination with” means that two (or more) different agents or treatments are administered to a subject as part of a defined treatment regimen for aAttorney Docket No.62801.72WO01 particular disease or condition. The treatment regimen defines the doses and periodicity of administration of each agent such that the effects of the separate agents on the subject overlap. In some embodiments, the delivery of the two or more agents is simultaneous or concurrent and the agents may be co-formulated. In other embodiments, the two or more agents are not co-formulated and are administered in a sequential manner as part of a prescribed. In some embodiments, administration of two or more agents or treatments in combination is such that the reduction in a symptom, or other parameter related to the condition is greater than what would be observed with one agent or treatment delivered alone or in the absence of the other. The effect of the two treatments can be partially additive, wholly additive, or greater than additive (e.g., synergistic). Sequential or substantially simultaneous administration of each therapeutic agent can be effected by any appropriate route including, but not limited to, oral routes, intravenous routes, and intramuscular routes. The therapeutic agents can be administered by the same route or by different routes.

[0072] As used herein, the term “integrin” refers to a family of transmembrane cell-matrix adhesion proteins. Integrins are composed of two noncovalently associated transmembrane glycoprotein subunits called α and β. A variety of human integrin heterodimers are formed from about 9 types of β subunits and about 24 types of α subunits. This diversity is further increased by alternative splicing of some integrin RNAs. See, e.g., Mezu-Ndubuisi OJ, Maheshwari A. The role of integrins in inflammation and angiogenesis. Pediatr Res. 2021 May;89(7):1619-1626. doi: 10.1038 / s41390-020-01177-9. Epub 2020 Oct 7. PMID: 33027803; PMCID: PMC8249239; Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Integrins. Available from: https: / / www.ncbi.nlm.nih.gov / books / NBK26867 / ; Danen EHJ. Integrins: An Overview of Structural and Functional Aspects. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013. Available from: https: / / www.ncbi.nlm.nih.gov / books / NBK6259 / ; the entire contents of each of which are incorporated herein by reference for all purposes.

[0073] As used herein the term “ α4β7 integrin,” and the like, refers to the integrin composed of the α4 and β7 subunits. The amino acid sequence of an exemplary reference mature human α4 polypeptide is set forth in SEQ ID NO: 578. The amino acid sequence of an exemplary reference mature human β7 polypeptide is set forth in SEQ ID NO: 579.

[0074] As used herein, the term “isolated” with reference to a polypeptide, protein, or nucleicAttorney Docket No.62801.72WO01 acid molecule refers to a polypeptide, protein, or nucleic acid molecule that is substantially free of other cellular components with which it is associated in the natural state.

[0075] As used herein, the term “human interleukin 10” or “hIL-10” refers to the human immunomodulatory cytokine that mediates signaling through the human IL-10 Receptor. The amino acid sequence of an exemplary reference mature hIL-10 protein is set forth in SEQ ID NO: 2.

[0076] As used herein, the term “human IL-10 Receptor” or “hIL-10R” refers to the human heterodimeric cell surface complex comprised of hIL-10Rα and hIL-10Rβ, through which hIL-10 mediates signaling.

[0077] As used herein, the term “human IL-10 Receptor α” or “hIL-10Rα” refers to the alpha (α) subunit of the hIL-10 Receptor. The amino acid sequence of an exemplary reference mature hIL-10Rα polypeptide is set forth in SEQ ID NO: 4.

[0078] As used herein, the term “human IL-10 Receptor β” or “hIL-10Rβ” refers to the beta (β) subunit of the hIL-10 Receptor. The amino acid sequence of an exemplary reference mature hIL-10Rβ polypeptide is set forth in SEQ ID NO: 6.

[0079] As used herein the term “LIGHT” or “Tumor Necrosis Factor Ligand Superfamily Member 14” refers to the immunomodulatory cytokine of the TNFSF. The amino acid sequence of an exemplary reference membrane human LIGHT (hLIGHT) protein is set forth in SEQ ID NO: 11 and the amino acid sequence of an exemplary reference soluble hLIGHT protein is set forth in SEQ ID NO: 12.

[0080] As used herein the term “LIGHTR” or “Tumor Necrosis Factor Receptor Superfamily Member 14” refers to the receptor of the TNFSF that binds, e.g., LIGHT. The amino acid sequence of an exemplary reference immature human LIGHTR (hLIGHTR) protein is set forth in SEQ ID NO: 21 and the amino acid sequence of an exemplary reference mature hLIGHTR protein is set forth in SEQ ID NO: 22.

[0081] As used herein the term “LTβR” or “Tumor Necrosis Factor Receptor Superfamily Member 3” refers to the receptor of the TNFSF that binds, e.g., LIGHT. The amino acid sequence of an exemplary reference immature human LTβR (hLTβR) protein is set forth in SEQ ID NO: 29 and the amino acid sequence of an exemplary reference mature hLTβR protein is set forth in SEQ ID NO: 30.

[0082] As used herein the term “LTα” or “Lymphotoxin α” or “Tumor Necrosis Factor LigandAttorney Docket No.62801.72WO01 Superfamily Member 1” refers to the multifunctional immunomodulatory cytokine of the TNFSF. The amino acid sequence of an exemplary reference immature form of human LTα (hTNFα) protein is set forth in SEQ ID NO: 9 and the amino acid sequence of an exemplary mature form of hLTα protein is set forth in SEQ ID NO: 10.

[0083] As used herein the term “MADCAM-1” or “mucosal vascular addressin cell adhesion molecule 1” refers to the endothelial cell adhesion molecule that interacts preferentially with specific integrins, including, e.g., α4β7 integrin. The amino acid sequence of an exemplary reference immature form of human MADCAM-1 (hMADCAM-1) is set forth in SEQ ID NO: 581; and the amino acid sequence of an exemplary mature form of hMADCAM-1is set forth in SEQ ID NO: 582.

[0084] As used herein, the term “moiety” is used generically to describe any macro or micro molecule that can be operably connected to a protein described herein. Exemplary moieties include, but are not limited small molecules, polypeptides, nucleic acid molecules (e.g., DNA, RNA), carbohydrates, lipids, synthetic polymers (e.g., polymers of PEG).

[0085] As used herein, the term “modified nucleotide,” “nucleotide modification,” or use of the term “modification” and the like in reference to a nucleotide or nucleic acid sequence refers to a nucleotide comprising a chemical modification, e.g., a modified sugar moiety, a modified nucleobase, and / or a modified internucleoside linkage, or any combination thereof. Exemplary modifications are provided herein, see, e.g., § 5.12.2. In certain embodiments of the instant disclosure, inclusion of a deoxynucleotide - which is acknowledged as a naturally occurring form of nucleotide - if present within an RNA molecule is considered to constitute a modified nucleotide.

[0086] As used herein, the term “obtaining a sample” refers to the acquisition of a sample. The term includes the direct acquisition from a subject and the indirect acquisition through one or more third parties wherein one of the third parties directly acquired the sample from the subject.

[0087] As used herein, the term “operably connected” refers to the linkage of two moieties in a functional relationship. For example, a polypeptide is operably connected to another polypeptide when they are linked (either directly or indirectly via a peptide linker) in frame such that both polypeptides are functional (e.g., a fusion protein described herein). Or for example, a transcription regulatory nucleic acid molecule e.g., a promoter, enhancer, or other expression control element is operably linked to a nucleic acid molecule that encodes a protein if it affects the transcription ofAttorney Docket No.62801.72WO01 the nucleic acid molecule that encodes the protein. The term “operably connected” can also refer to the conjugation of a moiety to e.g., a nucleic acid molecule or polypeptide (e.g., the conjugation of a PEG polymer to a protein).

[0088] The determination of “percent identity” between two sequences (e.g., peptide or protein (amino acid sequences) or polynucleotide (nucleic acid sequences)) can be accomplished using a mathematical algorithm. A specific, non-limiting example of a mathematical algorithm utilized for the comparison of two sequences is the algorithm of Karlin S & Altschul SF (1990) PNAS 87: 2264-2268, modified as in Karlin S & Altschul SF (1993) PNAS 90: 5873-5877, each of which is herein incorporated by reference in its entirety. Such an algorithm is incorporated into the NBLAST and XBLAST programs of Altschul SF et al., (1990) J Mol Biol 215: 403, which is herein incorporated by reference in its entirety. BLAST nucleotide searches can be performed with the NBLAST nucleotide program parameters set, e.g., for score=100, wordlength=12 to obtain nucleotide sequences heterologous to a nucleic acid molecule described herein. BLAST protein searches can be performed with the XBLAST program parameters set, e.g., to score 50, wordlength=3 to obtain amino acid sequences heterologous to a protein molecule described herein. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul SF et al., (1997) Nuc Acids Res 25: 3389-3402, which is herein incorporated by reference in its entirety. Alternatively, PSI BLAST can be used to perform an iterated search which detects distant relationships between molecules (Id.). When utilizing BLAST, Gapped BLAST, and PSI Blast programs, the default parameters of the respective programs (e.g., of XBLAST and NBLAST) can be used (see, e.g., National Center for Biotechnology Information (NCBI) on the worldwide web, ncbi.nlm.nih.gov). Another specific, non-limiting example of a mathematical algorithm utilized for the comparison of sequences is the algorithm of Myers and Miller, 1988, CABIOS 4:11-17, which is herein incorporated by reference in its entirety. Such an algorithm is incorporated in the ALIGN program (version 2.0) which is part of the GCG sequence alignment software package. When utilizing the ALIGN program for comparing amino acid sequences, a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4 can be used. The percent identity between two sequences can be determined using techniques similar to those described above, with or without allowing gaps. In calculating percent identity, typically only exact matches are counted.

[0089] As used herein, the term “pharmaceutical composition” means a composition that isAttorney Docket No.62801.72WO01 suitable for administration to an animal, e.g., a human subject, and comprises a therapeutic agent and a pharmaceutically acceptable carrier or diluent. A “pharmaceutically acceptable carrier or diluent” means a substance intended for use in contact with the tissues of human beings and / or non-human animals, and without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable therapeutic benefit / risk ratio.

[0090] As used herein, the term “plurality” means 2 or more (e.g., 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 9 or more, or 10 or more).

[0091] As used herein, the term “poly(A) sequence,” refers to a sequence of adenosine nucleotides, typically located at the 3'-end of a coding linear RNA, of up to about 1000 adenosine nucleotides. In some embodiments, the poly(A) sequence is essentially homopolymeric, e.g., a poly(A) sequence of e.g., 100 adenosine nucleotides having essentially the length of 100 nucleotides. In other embodiments, the poly(A) sequence may be interrupted by at least one nucleotide different from an adenosine nucleotide, e.g., a poly(A) sequence of e.g., 100 adenosine nucleotides may have a length of more than 100 nucleotides (comprising 100 adenosine nucleotides and in addition said at least one nucleotide - or a stretch of nucleotides - different from an adenosine nucleotide). It has to be understood that “poly(A) sequence” as defined herein typically relates to mRNA - however in the context of the invention, the term likewise relates to corresponding sequences in a DNA molecule (e.g., a “poly(T) sequence”).

[0092] The terms “polynucleotide” and “nucleic acid molecule” are used interchangeably herein and refer to a polymer of DNA or RNA. The nucleic acid molecule can be single-stranded or double-stranded; contain natural, non-natural, or altered nucleotides; and contain a natural, non- natural, or altered internucleotide linkage, such as a phosphoroamidate linkage or a phosphorothioate linkage, instead of the phosphodiester found between the nucleotides of an unmodified nucleic acid molecule. Nucleic acid molecules include, but are not limited to, all nucleic acid molecules which are obtained by any means available in the art, including, without limitation, recombinant means, e.g., the cloning of nucleic acid molecules from a recombinant library or a cell genome, using ordinary cloning technology and polymerase chain reaction, and the like, and by synthetic means. The skilled artisan will appreciate that, except where otherwise noted, nucleic acid sequences set forth in the instant application will recite thymidine (T) in a representative DNA sequence but where the sequence represents RNA (e.g., mRNA), the thymidines (Ts) would be substituted for uracils (Us). Thus, any of the RNA molecules encodedAttorney Docket No.62801.72WO01 by a DNA identified by a particular sequence identification number may also comprise the corresponding RNA (e.g., mRNA) sequence encoded by the DNA, where each thymidine (T) of the DNA sequence is substituted with uracil (U).

[0093] As used herein, the terms “protein” and “polypeptide” refers to a polymer of at least 2 (e.g., at least 5) amino acids linked by a peptide bond. The term “polypeptide” does not denote a specific length of the polymer chain of amino acids. It is common in the art to refer to shorter polymers of amino acids (e.g., approximately 2-50 amino acids) as peptides; and to refer to longer polymers of amino acids (e.g., approximately over 50 amino acids) as polypeptides. However, the terms “peptide” and “polypeptide” and “protein” are used interchangeably herein. In some embodiments, the protein is folded into its three-dimensional structure. Where linear polypeptides are contemplated herein (i.e., primary structure (amino acid sequence)), it should be understood that proteins folded into their three-dimensional structure are also provided herein. Where proteins are contemplated herein (i.e., folded into their three-dimensional structure) polypeptides in their primary structure (i.e., the amino acid sequence) are also provided herein.

[0094] A “prophylactic” treatment is a treatment administered to a subject who does not exhibit signs of a disease or exhibits only early signs for the purpose of decreasing the risk of developing pathology.

[0095] The terms “RNA” and “polyribonucleotide” are used interchangeably herein and refer to macromolecules that include multiple ribonucleotides that are polymerized via phosphodiester bonds. Ribonucleotides are nucleotides in which the sugar is ribose. RNA may contain modified nucleotides; and contain natural, non-natural, or altered internucleotide linkages, such as a phosphoroamidate linkage or a phosphorothioate linkage, instead of the phosphodiester linkage found between the nucleotides of an unmodified nucleic acid molecule.

[0096] As used herein, the term “sample” encompass a variety of biological specimens obtained from a subject. Exemplary sample types include, e.g., blood and other liquid samples of biological origin (including, but not limited to, whole-blood, peripheral blood mononuclear cells (PBMCs), serum, plasma, urine, saliva, amniotic fluid, stool, synovial fluid, etc.), nasopharyngeal swabs, solid tissue samples such as biopsies (or cells derived therefrom and the progeny thereof), tissue cultures (or cells derived therefrom and the progeny thereof), and cell cultures (or cells derived therefrom and the progeny thereof). The term also includes samples that have been manipulated in any way after their procurement from a subject, such as by centrifugation, filtration,Attorney Docket No.62801.72WO01 washing, precipitation, dialysis, chromatography, lysis, treatment with reagents, enriched for certain cell populations, refrigeration, freezing, staining, etc.

[0097] As used herein the term “TL1A” or “Tumor Necrosis Factor Ligand Superfamily Member 15” refers to the immunomodulatory cytokine of the TNFSF. The amino acid sequence of an exemplary reference membrane human TL1A (hTL1A) protein is set forth in SEQ ID NO: 15 and the amino acid sequence of an exemplary reference soluble hTL1A protein is set forth in SEQ ID NO: 16.

[0098] As used herein the term “TNFα” or “Tumor Necrosis Factor α” or “Tumor Necrosis Factor Ligand Superfamily Member 2” refers to the multifunctional immunomodulatory cytokine of the TNFSF. The amino acid sequence of an exemplary reference membrane human TNFα (hTNFα) protein is set forth in SEQ ID NO: 7 and the amino acid sequence of an exemplary reference soluble hTNFα protein is set forth in SEQ ID NO: 8.

[0099] As used herein the term “TNFR1” or “Tumor Necrosis Factor Receptor Superfamily Member 1A” refers to the receptor of the TNFSF that binds, e.g., TNFα. TNFR1 can be expressed both as a transmembrane protein and as a secreted protein through proteolytic processing. The amino acid sequence of an exemplary reference immature human TNFR1 (hTNFR1) protein is set forth in SEQ ID NO: 17 and the amino acid sequence of an exemplary reference mature hTNFR1 protein is set forth in SEQ ID NO: 18.

[0100] As used herein the term “TNFR2” or “Tumor Necrosis Factor Receptor Superfamily Member 1B” refers to the receptor of the TNFSF that binds, e.g., TNFα. The amino acid sequence of an exemplary reference immature human TNFR2 (hTNFR2) protein is set forth in SEQ ID NO: 19 and the amino acid sequence of an exemplary reference mature hTNFR2 protein is set forth in SEQ ID NO: 20.

[0101] As used herein, the term “translatable RNA” refers to any RNA that encodes at least one polypeptide and can be translated to produce the encoded protein in vitro, in vivo, in situ or ex vivo. A translatable RNA may be an mRNA or a circular RNA encoding a polypeptide.

[0102] The term “(scFv)2” as used herein refers to an antibody that comprises a first and a second scFv operably connected (e.g., via a peptide linker). The first and second scFv can specifically bind the same or different antigens. In some embodiments, the first and second scFv are operably connected by a peptide linker.

[0103] The term “scFv-Fc” as used herein refers to an antibody that comprises a scFv operablyAttorney Docket No.62801.72WO01 linked (e.g., via a peptide linker) to an Fc domain or subunit of an Fc domain. In some embodiments, a scFv is operably connected to only a first Fc domain of a first and a second Fc domain pair. In some embodiments, a first scFv is operably connected to a first Fc domain and a second scFv is operably connected to a second Fc domain of a first and second Fc domain pair.

[0104] The term “(scFv)2-Fc” as used herein refers to a (scFv)2 operably linked (e.g., via a peptide linker) to an Fc domain or a subunit of an Fc domain. In some embodiments, a (scFv)2 is operably connected to only a first Fc domain of a first and a second Fc domain pair. In some embodiments, a first (scFv)2 is operably connected to a first Fc domain and a second (scFv)2 is operably connected to a second Fc domain of a first and second Fc domain pair.

[0105] As used herein, the term “single domain antibody” or “sdAb” refers to an antibody having a single monomeric variable antibody domain. A sdAb is able to specifically bind to a specific antigen. A VHH (as defined herein) is an example of a sdAb.

[0106] As used herein, the term “signal peptide” or “signal sequence” refers to a sequence (e.g., an amino acid sequence) that can direct the transport or localization of a protein to a certain organelle, cell compartment, or extracellular export. The term encompasses both the signal sequence peptide and the nucleic acid sequence encoding the signal peptide. Thus, references to a signal peptide in the context of a nucleic acid refers to the nucleic acid sequence encoding the signal peptide.

[0107] As used herein, the term “specifically binds” refers to preferential interaction, i.e., significantly higher binding affinity, between a first protein (e.g., a ligand) and a second protein (e.g., the ligand’s cognate receptor) relative to other amino acid sequences. Herein, when a first protein is said to “specifically bind” to a second protein, it is understood that the first protein specifically binds to an epitope of the second protein. The term “epitope” refers to the portion of the second protein that the first protein specifically recognizes. The term specifically binds includes molecules that are cross reactive with the same epitope of a different species. For example, an antibody that specifically binds human CD30L may be cross reactive with CD30L of another species (e.g., cynomolgus, murine, etc.), and still be considered herein to specifically bind human CD30L. A protein can specifically bind more than one different protein.

[0108] As used herein, the term “subject” includes any animal, such as a human or other animal. In some embodiments, the subject is a vertebrate animal (e.g., mammal, bird, fish, reptile, or amphibian). In some embodiments, the subject is a human. In some embodiments, the methodAttorney Docket No.62801.72WO01 subject is a non-human mammal. In some embodiments, the subject is a non-human mammal is such as a non-human primate (e.g., monkeys, apes), ungulate (e.g., cattle, buffalo, sheep, goat, pig, camel, llama, alpaca, deer, horses, donkeys), carnivore (e.g., dog, cat), rodent (e.g., rat, mouse), or lagomorph (e.g., rabbit). In some embodiments, the subject is a bird, such as a member of the avian taxa Galliformes (e.g., chickens, turkeys, pheasants, quail), Anseriformes (e.g., ducks, geese), Paleaognathae (e.g., ostriches, emus), Columbiformes (e.g., pigeons, doves), or Psittaciformes (e.g., parrots).

[0109] As used herein, the term “therapeutically effective amount” of a therapeutic agent refers to any amount of the therapeutic agent that, when used alone or in combination with another therapeutic agent, improves a disease condition, e.g., protects a subject against the onset of a disease (or infection); improves a symptom of disease or infection, e.g., decreases severity of disease or infection symptoms, decreases frequency or duration of disease or infection symptoms, increases disease or infection symptom-free periods; prevents or reduces impairment or disability due to the disease or infection; or promotes disease (or infection) regression. The ability of a therapeutic agent to improve a disease condition can be evaluated using a variety of methods known to the skilled practitioner, such as in human subjects during clinical trials, in animal model systems predictive of efficacy in humans, or by assaying the activity of the agent in in vitro assays.

[0110] As used herein, the terms “treat,” treating,” “treatment,” and the like refer to reducing or ameliorating a disease or infection and / or symptom(s) associated therewith or obtaining a desired pharmacologic and / or physiologic effect. It will be appreciated that, although not precluded, treating a disease or infection does not require that the disease or infection, or symptom(s) associated therewith be completely eliminated. In some embodiments, the effect is therapeutic, i.e., without limitation, the effect partially or completely reduces, diminishes, abrogates, abates, alleviates, decreases the intensity of, or cures a disease and / or adverse symptom attributable to the disease or infection. In some embodiments, the effect is preventative, i.e., the effect protects or prevents an occurrence or reoccurrence of a disease or infection. To this end, the presently disclosed methods comprise administering a therapeutically effective amount of a composition as described herein.

[0111] As used herein, the term “variant” or “variation” with reference to a nucleic acid molecule, refers to a nucleic acid molecule that comprises at least one substitution, alteration, inversion, addition, or deletion of nucleotide compared to a reference nucleic acid molecule. AsAttorney Docket No.62801.72WO01 used herein, the term “variant” or “variation” with reference to a protein refers to a protein that comprises at least one substitution, alteration, inversion, addition, or deletion of an amino acid residue compared to a reference protein.

[0112] As used herein, the term “variant Ig Fc fusion protein” refers to a fusion protein comprising an Ig Fc region, wherein the Ig Fc region comprises one or more variation (e.g., one or more amino acid substitution, deletion, or addition)) that decreases or abolishes one or more Fc effector function, relative to a reference Ig Fc fusion protein that does not comprise the one or more variation.

[0113] The terms “VL” and “VL domain” are used interchangeably to refer to the light chain variable region of an antibody.

[0114] The terms “VH” and “VH domain” are used interchangeably to refer to the heavy chain variable region of an antibody.

[0115] The term “VHH” as used herein refers to a type of single domain antibody (sdAb) that has a single monomeric heavy chain variable antibody domain (VH). Such antibodies can be found in or produced from camelid mammals (e.g., camels, llamas) which are naturally devoid of light chains or synthetically produced.

[0116] As used herein, the term “5'-untranslated region” or “5'-UTR” refers to a part of a nucleic acid molecule located 5' (i.e., “upstream”) of a coding sequence and which is not translated into protein. Typically, a 5'-UTR starts with the transcriptional start site and ends before the start codon of the coding sequence. A 5'-UTR may comprise elements for controlling gene expression, also called regulatory elements. Such regulatory elements may be, e.g., ribosomal binding sites, miRNA binding sites etc. The 5'-UTR may be post-transcriptionally modified, e.g., by enzymatic or post-transcriptional addition of a 5'-cap structure.

[0117] As used herein the term “3'-untranslated region” or “3'-UTR” refers to a part of a nucleic acid molecule located 3' (i.e., downstream) of a coding sequence and which is not translated into protein. A 3'-UTR may located between a coding sequence and an (optional) terminal poly(A) sequence of a nucleic acid sequence. A 3'-UTR may comprise elements for controlling gene expression, also called regulatory elements. Such regulatory elements may be, e.g., ribosomal binding sites, miRNA binding sites etc. 5.2 Immunomodulatory Proteins and Fusion Proteins ThereofAttorney Docket No.62801.72WO01 5.2.1 Combinatorial Immunomodulatory Proteins

[0118] The present disclosure provides, inter alia, fusion proteins (e.g., immunomodulatory fusion proteins (IFPs)) (and functional fragments and variants thereof) that e.g., comprise a plurality of immunomodulatory proteins (and combination regimens comprising a plurality of immunomodulatory proteins or fusion proteins described herein). Immunomodulatory proteins described herein include, e.g., those described in §§ 5.2.1.1, 5.2.1.2, 5.2.1.3, and 5.2.1.4. Immunomodulatory proteins described herein include, e.g., those that specifically bind to the IL- 10R (e.g., human IL-10R)) (see, e.g., § 5.2.1.1); those that specifically bind to TL1A (e.g., human TL1A)) (see, e.g., § 5.2.1.2); those that specifically bind to TNFα (e.g., human TNFα)) (see, e.g., § 5.2.1.3); and those that specifically bind to CD30L (e.g., human CD30L)) (see, e.g., § 5.2.1.4). Immunomodulatory proteins also include human proteins that specifically bind one (or more) of hIL-10R (e.g., hIL-10 (e.g., SEQ ID NO: 2)), hTL1A, hTNFα, or hCD30L.

[0119] The amino acid sequence of various reference proteins referred to throughout the instant disclosure is set forth Table 1 below. Table 1. The Amino Acid Sequence of Human Reference Proteins. Description Amino Acid Sequence SEQ ID NOAttorney Docket No.62801.72WO01 Peptide)TNTRFSVDEVTLTVGSVNLEIHNGFILGKIQLPRPKMAPANDTYES IFSHFREYEIAIRKVPGNFTFTHKKVKHENFSLLTSGEVGEFCVQV KPSVASRSNKGMWSKEECISLTRQYFTVTNVIIFFAFVLLLSGALAAttorney Docket No.62801.72WO01 SPCGRATSSSRVWWDSSFLGGVVHLEAGEKVVVRVLDERLVRLRDG TRSYFGAFMV LIQERRSHEVNPAAHLTGANSSLTGSGGPLLWETQLGLAFLRGLSYAttorney Docket No.62801.72WO01 MAPVAVWAALAVGLELWAAAHALPAQVAFTPYAPEPGSTCRLREYY DQTAQMCCSKCSPGQHAKVFCTKTSDTVCDSCEDSTYTQLWNWVPE CLSCGSRCSSDQVETQACTREQNRICTCRPGWYCALSKQEGCRLCAAttorney Docket No.62801.72WO01 Immature Form QACDEQASQVALENCSAVADTRCGCKPGWFVECQVSQCVSSSPFYC QPCLDCGALHRHTRLLCSRRDTDCGTCLPGFYEHGDGCVSCPTSTL GSCPERCAAVCGWRQMFWVQVLLAGLVVPLLLGATLTYTYRHCWPHAttorney Docket No.62801.72WO01 Form APFKKSWAYLQVAKHLNKTKLSWNKDGILHGVRYQDGNLVIQFPGL YFIICQLQFLVQCPNNSVDLKLELLINKHIKKQALVTVCESGMQTK HVYQNLSQFLLDYLQVNTTISVNVDTFQYIDTSTFPLENVLSIFLY5.2.1.1 IL-10R Binding Proteins

[0120] In some aspects and embodiments, a fusion protein described herein (or a combination regimen described herein) comprises a protein that specifically binds the hIL-10R (e.g., hIL-10Rβ, hIL-10Rα).

[0121] The amino acid sequence of proteins capable of specifically binding the hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) is set forth in Table 2 (SEQ ID NOS: 34-386). The amino acid sequence of the mature form of the proteins (i.e., lacking the native signal peptide) is set forth in SEQ ID NOS: 212-386. The amino acid sequence of the immature form of the proteins (i.e., containing the native signal peptide) is set forth in SEQ ID NOS: 34-211.

[0122] The signal peptides have been computationally predicted using standard methods (see, e.g., Teufel, F., Almagro Armenteros, J.J., Johansen, A.R. et al. SignalP 6.0 predicts all five types of signal peptides using protein language models. Nat Biotechnol (2022).Attorney Docket No.62801.72WO01 https: / / doi.org / 10.1038 / s41587-021-01156-3 (hereinafter referred to as “Teufel 2022”), the entire contents of which is incorporated by reference herein for all purposes). A person of ordinary skill in the art would know how to experimentally identify and / or validate a computationally predicted signal peptide using standard methods known in the art, e.g., expression of the immunomodulatory protein from a host cell and sequencing of the intracellular form and the extracellular form of the expressed protein (see, e.g., Zhang Z, Henzel WJ. Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein Sci. 2004;13(10):2819-2824. doi:10.1110 / ps.04682504 (hereinafter referred to as “Zhang 2004”), the entire contents of which is incorporated by reference herein for all purposes). Table 2. The Amino Acid Sequence of IL-10R Binding Proteins. Description Amino Acid Sequence SEQ ID NOAttorney Docket No.62801.72WO01 FLLQS MLSVMVSSSLVLIVFFLGASEEAKPATTTIKNTKPQCRPEDYATR IMP-8 LQDLRVTFHRVKPTLQREDDYSVWLDGTVVKGCWGCSVMDWLLRRAttorney Docket No.62801.72WO01 with signal peptideLPHMLRELRAAFGKVKTFFQMKDQLNSMLLTQSLLDDFKGYLGCQALSEMIQFYLEEVMPQAENHGPDIKEHVNSLGEKLKTLRLRLRRC HRFLPCENKSKAVEQVKRVFNMLQERGVYKAMSEFDIFINYIESYAttorney Docket No.62801.72WO01 ALSEMIQFYLEEVMPQAENHGPDIKEHVNSLGEKLKTLRLRLRRC HRFLPCENKSKAVEQVKRVFNMLQERGDYKAMSEFDIFINYIESY MTTKSAttorney Docket No.62801.72WO01 IMP-39 MSNNKILVCVAIILTYTLYTNAYCVEYLESEEDKQQCGSNGASSS with signal peptide SPHMLRELRAAFGKVKTFFQMKDQLNSMLLTQSLLDDFKGYLGCQ ALSEMIQFYLEEVMPQAENHGPDVKEHVNSLGEKLKTLRLRLRRC 72Attorney Docket No.62801.72WO01 IMP-51 MERRLVVTLQCLVLLYLAPECGGTDQCDNFPQMLRDLRDAFSRVK with signal peptide TFFQTKDEVDNLLLKESLLEDFKGYLGCQALSEMIQFYLEEVMPQ AENQDPEAKDHVNSLGENLKTLRLRLRRCHRFLPCENKSKAVEQI 84Attorney Docket No.62801.72WO01 PLLTQKLLEDFKGYLGCQALSEMIQFYLEEVMPQAEDSNPSAKDS VTSLGEKLKTLRLRLRRCHRFLPCENKSKAVENLKSKFGDLGNQG VHKAMSEFDIFINYIETYMTTKMKAttorney Docket No.62801.72WO01 IMP-76 MLSVMVSSSLVLIVFFLGASEEAKPATTTTIKNTKPQCRPEDYAT with signal peptide RLQDLRVTFDRVKPTLQREDDYSVWLDGTVVKGCWGCSVMDWLLR RYLEIVFPAGDHVYPGLKTELHSMRSTLESIYKDMRQCPLLGCGD 109Attorney Docket No.62801.72WO01 DKSVISRLSQEAERKSDNGTRKGLSELDTLFSRLEEYLHSRK IMP-89 MLSVMVSSSLVLIVFFLGASEEAKPAATTTTTIKNTKPQCRPEDY with i n l tid ATRLQDLRVTFHRVKPTLQREDDYSVWLDGTVVKGCWGCSVMDWLAttorney Docket No.62801.72WO01 with signal peptide YATRLQDLRVTFHRVKPTLQREDDYSVWLDGTVVKGCWGCSVMDW LLRRYLEIVFPAGDHVYPGLKTELHSMRSTLESIYKDMRQCPLLG CGDKSVISRLSQKAERKSDNGTRKGLSELDTLFSRLEEYLHSRKAttorney Docket No.62801.72WO01 CGDKSVISRLSQEAERKSDNGTRKGLSELDTLFSRLEEYLHSRK IMP-114 MLSVMVSSSLVMIVFFLGASEEAKPATTTTTIKNTKPQCRPEDYA with i n l tid TRLQDLCVTFHRVKPTLQREDDYSVWLDGTVVKGCWGCSVMDWLLAttorney Docket No.62801.72WO01 IMP-126 MKTNTKIILFCYVILYVFSCTVASAKKCDDVSFDYILKDLRSEFS with signal peptide KIKSFVQNNDKENMMLLSQSMLDKLTSCIGCKSLSDMIKFYLNDV LPNAEKIEHIKNKITSIGEKLKSLKEKLISCDFLHCENHDEIKAV 159Attorney Docket No.62801.72WO01 IMP-138 MININILSLLILILSIYANAIIDTCYDDQERERTKSNSISSVTPE with signal peptide MCKGLKQLVSTKLKDARQKEKSVRDYFTSRDNDLDFMLLQGVKET HKKTCGCYVLYLLLSFYGKTIRDTIQSNKHKNLNTELTNLAVSVL 171Attorney Docket No.62801.72WO01 KKELACGPAPFDMIKLYHDTKEYGADNIMGTLDTPFQYFVIV IMP-150 MLALAMVLMALGPLSTNAMYVQHGRGDYCTTTVRADIASAISGMR with i n l tid AEYDSGLGHYFKSLVPHPDNPYDTDDYKYMINNTNSYNCHALQSTAttorney Docket No.62801.72WO01 KSKAVEQVKSAFSKLQEKGVYKAMSEFDIFINYIEAYMTTKMKN IMP-163 MFRALLLCCLALLAGVWADNRYDGQDGNDCPTLPTSLPHMLHELR with i n l tid AAFSRVKTFFQMKDQLDNMLLDGSLLEDFKGYLGCQALSEMIQFYAttorney Docket No.62801.72WO01 with signal peptide LQDLRVTFHRVKPTLVGHVGDHVYPGLKTELHSMRSTLESIYKDM RQCEAERKSDNGTRKGLSELDTLFSRLEEYLHSRK IMP-273 MHSSALLCCLVLLTGVRASPGQGTQSENSCTHFPGNLPNMLRDLRAttorney Docket No.62801.72WO01 IMP-13 YCVEYEESEEDRQQCSSSNFPASLPHMLRELRAAFGKVKTFFQMK without signal DQLNSMLLTQSLLDDFKGYLGCQALSEMIQFYLEEVMPQAENHGP e tide DIKEHVNSLGEKLKTLRLRLRRCHRFLPCENKSKAVEQVKRVFNM 221Attorney Docket No.62801.72WO01 peptide PDIKEHVNSLGEKLKTLRLRLRRCHRFLPCENKSKAVEQVKRVFN MLQERGVYKAMSEFDIFINYIESYMTTKM IMP-26 YCVEYEESDEDKQQCSSSTGAPASLPHMLRELRAAFGKVKTFFQMAttorney Docket No.62801.72WO01 IMP-38 YCVEYLESEEDKQQCGSNGASSSSPHMLRELRAAFGKVKTFFQMK without signal DQLNSMLLTQSLLDDFKGYLGCQALSEMIQFYLEEVMPQAENHGP e tide DVKEHVNSLAEKLKTLRLRLRRCHRFLPCENKSKAVEQVKRVFNM 246Attorney Docket No.62801.72WO01 peptide LRLRRCHRFLPCENKSKAVEQIKNAFNKLQEKGIYKAMSEFDIFI NYIEAYMTIKAR IMP-51 TDQCDNFPQMLRDLRDAFSRVKTFFQTKDEVDNLLLKESLLEDFKAttorney Docket No.62801.72WO01 IMP-63 TANNRAQKCFCFDGSNAGNSEETNTAAFQKKCDSEIPESLPYMLR without signal DLRNSSVQTRRYFQEKDEENSPLLTQKLLEDFKGYLGCQALSEMI e tide QFYLEEVMPQAEDSNPSAKDSVTSLGEKLKTLRLRLRRCHRFLPC 271Attorney Docket No.62801.72WO01 peptide TLESIYKDMRQCPLLGCGDKSVISRLSQEAERKSDNGTRKGLSEL DTLFSRLEEYLHSRK IMP-76 ATTTTIKNTKPQCRPEDYATRLQDLRVTFDRVKPTLQREDDYSVWAttorney Docket No.62801.72WO01 IMP-88 AATTTTIKNTKPQCRPEDYATRLQDLRVTFHRVKPTLQREDDYSV without signal WLDGTVVKGCWGCSVMDWLLRRYLEIVFPAGDHVYPGLKTELHSM e tide RSTLESIYKDMRQCPLLGCGDKSVISRLSQEAERKSDNGTRKGLS 296Attorney Docket No.62801.72WO01 peptide STLESIYKDMRQCPLLGCGDKSVISRLSQEAERKSDNGTRKGLSE LDTLFSRLEEYLHSRK IMP-101 ATTTTTTTIKNTKPQCRPEDYATRLQDLRVTFHRVKPTLQREDDYAttorney Docket No.62801.72WO01 IMP-113 ATTTTTTIKNTKPQCRPEDYATRLQDLRVTFHRVKPTLQREDDYS without signal VWLDGTVVKGCWRCSVMDWLLRRYLEIVFPAGDHVYPGLKTELHS e tide MRSTLESIYKDMRQCPLLGCGDKSVISRLSQEAERKSDNGTRKGL 321Attorney Docket No.62801.72WO01 peptide KLKSLKEKLISCDFLHCENNDEIKTVKAIFNKLKDKGIYKAMGEF DIFINYVEKYIVKT IMP-126 KKCDDVSFDYILKDLRSEFSKIKSFVQNNDKENMMLLSQSMLDKLAttorney Docket No.62801.72WO01 LKRIEEYMKEHGDDAIYKVIGEIEFLFQAIEKHVY IMP-139 NSIIDMCYDDQERERTKSNSISSITPDMCKGLKQLVATKLKDARQ with t i n l KEKLVNSYFTSRDNDLTYMLLQGVRETHKKPCGCYVLYLLLTFYRAttorney Docket No.62801.72WO01 without signal IYPSDVMNELASTSVACDAIKKVLTMNIGILPNVTAAYPDKKSEV peptide DEIGDNLSRLHQNIVNCRDFLKCEDLPHWHQMAENYKEKPMQGFS EMDFVFQSVEKFLVAKDVKNMKTKRKHAttorney Docket No.62801.72WO01 IMP-164 ATTAIKNTKPQCRPEDYATRLQDLRVTFHRVKPTLQREDDYSVWL without signal DGTVVKGCWGCSVMDWLLRRYLEIVFPAGDHVYPGLKTELHSMRS e tide TLESIYKDMRQCPLLGCGDKSVISRLSQEAERKSDNGTRKGLSEL 372Attorney Docket No.62801.72WO01 IYKAMSEFDIFINYIEAYMTMKIRN IMP-274 SPGQGTQSENSCTHFPGYLPNMLRDLRDAFSRVKTFFQMKDQLDN with i n l tid LLLKESLLEDFKGYLGCQALSEMIQFYLEEVMPQAENQDPDIKAHcid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein comprises an amino acid sequence at least 85% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein comprises an amino acid sequence at least 90% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein comprises an amino acid sequence at least 95% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein comprises an amino acid sequence at least 99% identical to the amino acid sequence of a protein set forth in Table 2.

[0124] In some embodiments, the IL-10R binding protein comprises an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein comprises an amino acid sequence 85% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein comprises an amino acid sequence 90% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein comprises an amino acid sequence 95% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein comprises an amino acid sequence 99% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein comprises an amino acid sequence 100% identical to the amino acid sequence of a protein set forth in Table 2.

[0125] In some embodiments, the IL-10R binding protein consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments,Attorney Docket No.62801.72WO01 the IL-10R binding protein consists of an amino acid sequence at least 85% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein consists of an amino acid sequence at least 90% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein consists of an amino acid sequence at least 95% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein consists of an amino acid sequence at least 99% identical to the amino acid sequence of a protein set forth in Table 2.

[0126] In some embodiments, the IL-10R binding protein consists of an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein consists of an amino acid sequence 85% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein consists of an amino acid sequence 90% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein consists of an amino acid sequence 95% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein consists of an amino acid sequence 99% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, the IL-10R binding protein consists of an amino acid sequence 100% identical to the amino acid sequence of a protein set forth in Table 2.

[0127] In some embodiments, the IL-10R binding protein comprises the amino acid sequence of a protein set forth in Table 2, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein comprises the amino acid sequence of a protein set forth in Table 2, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein comprises the amino acid sequence of a protein set forth in Table 2, and further consisting of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein comprises the amino acid sequence of a protein set forth in Table 2, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein comprises the amino acid sequence of a protein set forth in Table 2, and further consistingAttorney Docket No.62801.72WO01 of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein comprises the amino acid sequence of a protein set forth in Table 2, and further comprising or no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0128] In some embodiments, the IL-10R binding protein consists of the amino acid sequence of a protein set forth in Table 2, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein consists of the amino acid sequence of a protein set forth in Table 2, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein consists of the amino acid sequence of a protein set forth in Table 2, and further consisting of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein consists of the amino acid sequence of a protein set forth in Table 2, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein consists of the amino acid sequence of a protein set forth in Table 2, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein consists of the amino acid sequence of a protein set forth in Table 2, and further comprising or no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0129] In some embodiments, the IL-10R binding protein comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein comprises an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein comprises an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein comprises an amino acid sequence at least 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein comprises an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.Attorney Docket No.62801.72WO01

[0130] In some embodiments, the IL-10R binding protein comprises an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein comprises an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL- 10R binding protein comprises an amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein comprises an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein comprises an amino acid sequence 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34- 386. In some embodiments, the IL-10R binding protein comprises an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

[0131] In some embodiments, the IL-10R binding protein consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein consists of an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein consists of an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein consists of an amino acid sequence at least 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein consists of an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein consists of an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

[0132] In some embodiments, the IL-10R binding protein consists of an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein consists of an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL- 10R binding protein consists of an amino acid sequence 90% identical to the amino acid sequenceAttorney Docket No.62801.72WO01 set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein consists of an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, the IL-10R binding protein consists of an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34- 386.

[0133] In some embodiments, the IL-10R binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further comprising or consists of no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0134] In some embodiments, the IL-10R binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the IL-10R binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions,Attorney Docket No.62801.72WO01 deletions, etc.). In some embodiments, the IL-10R binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further consisting of no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0135] In some aspects and embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 85% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 90% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 95% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 99% identical to the amino acid sequence of a protein set forth in Table 2.

[0136] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 85% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein ((or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 90% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functionalAttorney Docket No.62801.72WO01 fragment / variant thereof) comprising an amino acid sequence 95% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 99% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 100% identical to the amino acid sequence of a protein set forth in Table 2.

[0137] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 85% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 90% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 95% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 99% identical to the amino acid sequence of a protein set forth in Table 2.

[0138] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 85% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments,Attorney Docket No.62801.72WO01 a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 90% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 95% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 99% identical to the amino acid sequence of a protein set forth in Table 2. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 100% identical to the amino acid sequence of a protein set forth in Table 2.

[0139] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 2, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 2, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 2, and further consisting of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 2, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 2, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).Attorney Docket No.62801.72WO01 In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 2, and further comprising or no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0140] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 2, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 2, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 2, and further consisting of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consists of the amino acid sequence of a protein set forth in Table 2, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 2, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 2, and further comprising or no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0141] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ IDAttorney Docket No.62801.72WO01 NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

[0142] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34- 386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acidAttorney Docket No.62801.72WO01 sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

[0143] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

[0144] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34- 386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.Attorney Docket No.62801.72WO01 In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

[0145] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further comprising or consists of no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0146] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described hereinAttorney Docket No.62801.72WO01 comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 34-386, and further consisting of no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). (i) Exemplary Properties of IL-10R Binding Proteins

[0147] In some embodiments, the IL-10R binding proteins described herein are immunosuppressive (e.g., when administered to a subject). In some embodiments, the IL-10R binding proteins described herein are anti-inflammatory (e.g., when administered to a subject). In some embodiments, the IL-10R binding proteins described herein suppress pro-inflammatory response (e.g., when administered to a subject).

[0148] In some embodiments, the IL-10R binding protein specifically binds hIL-10Rα. In some embodiments, the IL-10R binding protein specifically binds hIL-10Rβ. In some embodiments, the IL-10R binding protein specifically binds both hIL-10Rα and hIL-10Rβ. In some embodiments, the IL-10R binding protein specifically binds hIL-10Rα and does not bind hIL-10Rβ. In some embodiments, the IL-10R binding protein specifically binds hIL-10Rβ and does not bind hIL-10Rα. In some embodiments, the IL-10R binding protein specifically binds both hIL-10Rα and hIL-10Rβ but binds hIL-10Rα with higher affinity than hIL-10Rβ. In some embodiments, the IL-10R binding protein specifically binds both hIL-10Rα and hIL-10Rβ but binds hIL-10Rβ with higher affinity than hIL-10Rα.

[0149] In some embodiments, the IL-10R binding protein is a hIL-10R agonist. In someAttorney Docket No.62801.72WO01 embodiments, the IL-10R binding protein is a hIL-10Rα agonist. In some embodiments, the IL- 10R binding protein is a hIL-10Rβ agonist. In some embodiments, the IL-10R binding protein is a hIL-10Rα agonist and a hIL-10Rβ agonist. In some embodiments, the IL-10R binding protein is capable of inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling. 5.2.1.2 TL1A Binding Proteins

[0150] In some aspects and embodiments, a fusion protein described herein (or combination regimen described herein) comprises a protein that specifically binds the hTL1A.

[0151] The amino acid sequence of proteins capable of specifically binding hTL1A is set forth in Table 3 (SEQ ID NOS: 387-454). The amino acid sequence of the mature form of the proteins (i.e., lacking the native signal peptide) is set forth in SEQ ID NOS: 387-420. The amino acid sequence of the immature form of the proteins (i.e., containing the native signal peptide) is set forth in SEQ ID NOS: 421-454.

[0152] The signal peptides have been computationally predicted using standard methods (see, e.g., Teufel 2022). A person of ordinary skill in the art would know how to experimentally identify and / or validate a computationally predicted signal peptide using standard methods known in the art, e.g., expression of a protein from a host cell and sequencing of the intracellular form and the extracellular form of the expressed protein (see, e.g., Zhang 2004). Table 3. The Amino Acid Sequence of TL1A Binding Proteins. Description Amino Acid Sequence SEQ ID NOAttorney Docket No.62801.72WO01 IMP-182 STYTDSATGRTCSKCPPGTYRSADCGATTSTVCTACGAGTYTDKDN without native NLSACLACSTCNAATETEVSACTATANTVCACKAGYTLDANGKCV393si nal e tideAttorney Docket No.62801.72WO01 signal peptide IMP-199 DTYTDPTTGLTCKKCPPGTYLKKNCTATSPTVCKKCGPGQYTTKYN with t n tiv NLKKCNKCSTCDPTTEEVSQACTPTHDTVCKCKPGYSLNSKGRCV410Attorney Docket No.62801.72WO01 IMP-180 MGKNSLVLTIGVLMTLITLRSSFSADTFTDEETGLVCEKCPPGTYR with native signal EADCTETTKTVCKACGEGTFTDHPNNLPECKSCSTCDEATEVEVQK 425 e tide CTATANTVCACKDGFTVNEKGECVAttorney Docket No.62801.72WO01 peptideCTPTSNTVCTCKPGYVKDANGKCVIMP-197 MGKNSLVLTIGVLMTLITLRSSFSAQTYVDPATGLTCTLCPPGTYL with n tiv i n l KKPCTATSPTVCKPCGSGTYTSKPNALTKCQECTTCDPATERVVRP 442

[0153] In some aspects and embodiments, the TL1A binding protein comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein comprises an amino acid sequence at least 85% identicalAttorney Docket No.62801.72WO01 to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein comprises an amino acid sequence at least 90% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein comprises an amino acid sequence at least 95% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein comprises an amino acid sequence at least 99% identical to the amino acid sequence of a protein set forth in Table 3.

[0154] In some embodiments, the TL1A binding protein comprises an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein comprises an amino acid sequence 85% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein comprises an amino acid sequence 90% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein comprises an amino acid sequence 95% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein comprises an amino acid sequence 99% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein comprises an amino acid sequence 100% identical to the amino acid sequence of a protein set forth in Table 3.

[0155] In some embodiments, the TL1A binding protein consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein consists of an amino acid sequence at least 85% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein consists of an amino acid sequence at least 90% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein consists of an amino acid sequence at least 95% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein consists of an amino acid sequence at least 99% identical to the amino acid sequence of a protein set forth in Table 3.

[0156] In some embodiments, the TL1A binding protein consists of an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In someAttorney Docket No.62801.72WO01 embodiments, the TL1A binding protein consists of an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein consists of an amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein consists of an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein consists of an amino acid sequence 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein consists of an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387- 454.

[0157] In some embodiments, the TL1A binding protein consists of an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein consists of an amino acid sequence 85% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein consists of an amino acid sequence 90% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein consists of an amino acid sequence 95% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein consists of an amino acid sequence 99% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, the TL1A binding protein consists of an amino acid sequence 100% identical to the amino acid sequence of a protein set forth in Table 3.

[0158] In some embodiments, the TL1A binding protein comprises the amino acid sequence of a protein set forth in Table 3, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein comprises the amino acid sequence of a protein set forth in Table 3, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein comprises the amino acid sequence of a protein set forth in Table 3, and further consisting of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein comprises the amino acid sequence of aAttorney Docket No.62801.72WO01 protein set forth in Table 3, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein comprises the amino acid sequence of a protein set forth in Table 3, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein comprises the amino acid sequence of a protein set forth in Table 3, and further comprising or no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0159] In some embodiments, the TL1A binding protein consists of the amino acid sequence of a protein set forth in Table 3, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein consists of the amino acid sequence of a protein set forth in Table 3, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein consists of the amino acid sequence of a protein set forth in Table 3, and further consisting of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein consists of the amino acid sequence of a protein set forth in Table 3, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein consists of the amino acid sequence of a protein set forth in Table 3, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein consists of the amino acid sequence of a protein set forth in Table 3, and further comprising or no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0160] In some embodiments, the TL1A binding protein comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein comprises an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein comprises an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein comprises an amino acid sequence at least 95% identical to the amino acidAttorney Docket No.62801.72WO01 sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein comprises an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

[0161] In some embodiments, the TL1A binding protein comprises an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein comprises an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein comprises an amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein comprises an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein comprises an amino acid sequence 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein comprises an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387- 454.

[0162] In some embodiments, the TL1A binding protein consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein consists of an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein consists of an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein consists of an amino acid sequence at least 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, the TL1A binding protein consists of an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

[0163] In some embodiments, the TL1A binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein comprises the amino acidAttorney Docket No.62801.72WO01 sequence set forth in any one of SEQ ID NOS: 387-454, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further comprising or consists of no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0164] In some embodiments, the TL1A binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TL1A binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further consisting of no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0165] In some aspects and embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising anAttorney Docket No.62801.72WO01 amino acid sequence at least 85% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 90% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 95% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 99% identical to the amino acid sequence of a protein set forth in Table 3.

[0166] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 85% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein ((or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 90% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 95% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 99% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 100% identical to the amino acid sequence of a protein set forth in Table 3.

[0167] In some embodiments, a fusion protein described herein comprises a protein (or aAttorney Docket No.62801.72WO01 functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 85% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 90% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 95% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 99% identical to the amino acid sequence of a protein set forth in Table 3.

[0168] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 85% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 90% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 95% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 99% identical to the amino acid sequence of a protein set forth in Table 3. In some embodiments, a fusion protein described herein comprises aAttorney Docket No.62801.72WO01 protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 100% identical to the amino acid sequence of a protein set forth in Table 3.

[0169] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 3, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 3, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 3, and further consisting of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 3, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 3, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 3, and further comprising or no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0170] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 3, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises aAttorney Docket No.62801.72WO01 protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 3, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 3, and further consisting of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 3, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 3, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 3, and further comprising or no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0171] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 95% identical to the amino acid sequence set forth inAttorney Docket No.62801.72WO01 any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

[0172] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

[0173] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQAttorney Docket No.62801.72WO01 ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

[0174] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

[0175] In some embodiments, a fusion protein described herein comprises a protein (or aAttorney Docket No.62801.72WO01 functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further comprising or consists of no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0176] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions,Attorney Docket No.62801.72WO01 deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 387-454, and further consisting of no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). (i) Exemplary Properties of TL1A Binding Proteins

[0177] In some embodiments, the TL1A binding proteins described herein are immunosuppressive (e.g., when administered to a subject). In some embodiments, the TL1A binding proteins described herein are anti-inflammatory (e.g., when administered to a subject). In some embodiments, the TL1A binding proteins described herein suppress pro-inflammatory response (e.g., when administered to a subject). In some embodiments, the TL1A binding protein can act as a decoy receptor for a TNFSF ligand described herein.

[0178] In some embodiments, the TL1A binding protein is capable of specifically binding hTL1A. In some embodiments, the TL1A binding protein is capable of inhibiting or reducing (e.g., preventing) binding of hTL1A to hDR3.

[0179] In some embodiments, the TL1A binding proteins described herein bind a subset (e.g., one or more) TNFSF ligand. In some embodiments, the TL1A binding protein specifically binds TL1A. In some embodiments, the TL1A binding protein specifically binds hTL1A.

[0180] In some embodiments, the TL1A binding protein inhibits reduces (e.g., prevents) binding of TL1A to DR3. In some embodiments, the TL1A binding protein specifically binds to TL1A and inhibits reduces (e.g., prevents) binding of TL1A to DR3. In some embodiments, the TL1A binding protein inhibits reduces (e.g., prevents) binding of hTL1A to hDR3. In some embodiments, the TL1A binding protein specifically binds to hTL1A and inhibits reduces (e.g., prevents) binding of hTL1A to hDR3. In some embodiments, the TL1A binding protein inhibits reduces (e.g., prevents) DR3 signaling. In some embodiments, the TL1A binding protein inhibits reduces (e.g., prevents) DR3 signaling mediated by DR3 binding to TL1A. In some embodiments, the TL1A binding protein inhibits reduces (e.g., prevents) NFκB activation. In some embodiments, the TL1A binding protein inhibits reduces (e.g., prevents) NFκB activation mediating throughAttorney Docket No.62801.72WO01 DR3. In some embodiments, the TL1A binding protein inhibits reduces (e.g., prevents) NFκB activation mediated through DR3 binding to TL1A.

[0181] In some embodiments, the TL1A binding protein inhibits reduces (e.g., prevents) binding of TL1A to DcR3. In some embodiments, the TL1A binding protein specifically binds to TL1A and inhibits reduces (e.g., prevents) binding of TL1A to DcR3. In some embodiments, the TL1A binding protein inhibits reduces (e.g., prevents) binding of hTL1A to hDcR3. In some embodiments, the TL1A binding protein specifically binds to hTL1A and inhibits reduces (e.g., prevents) binding of hTL1A to hDcR3. In some embodiments, the TL1A binding protein inhibits reduces (e.g., prevents) DcR3 signaling. In some embodiments, the TL1A binding protein inhibits reduces (e.g., prevents) DcR3 signaling mediated by DcR3 binding to TL1A.

[0182] In some embodiments, the TL1A binding protein does not specifically binds one or more of TNFα, LIGHT, and / or FASL. In some embodiments, the TL1A binding protein does not specifically bind 2 or 3 of TNFα, LIGHT, and / or FASL. In some embodiments, the TL1A binding protein does not specifically bind TNFα, LIGHT, and / or FASL. In some embodiments, the TL1A binding protein does not specifically bind TNFα, LIGHT, and / or FASL. In some embodiments, the TL1A binding protein does not specifically bind a plurality of TNFα, LIGHT, and / or FASL.

[0183] In some embodiments, the TL1A binding protein does not specifically binds one or more of hTNFα, hLIGHT, and / or hFASL. In some embodiments, the TL1A binding protein does not specifically bind 2 or 3 of hTNFα, hLIGHT, and / or hFASL. In some embodiments, the TL1A binding protein does not specifically bind hTNFα, hLIGHT, and / or hFASL. In some embodiments, the TL1A binding protein does not specifically bind hTNFα, hLIGHT, and / or hFASL. In some embodiments, the TL1A binding protein does not specifically bind a plurality of hTNFα, hLIGHT, and / or hFASL.

[0184] In some embodiments, the TL1A binding protein does not inhibit or reduce (e.g., prevent) binding of one or more TNFSF ligand (e.g., TNFα, LIGHT, and / or FASL) to one or more of the TNFSF ligand’s (e.g., TNFα, LIGHT, and / or FASL) cognate receptor.

[0185] In some embodiments, the TL1A binding protein exhibits one or more (e.g., 1, 2, 3, 4, and / or 5) of (a) does not inhibit or reduce (e.g., prevent)binding of TNFα to TNFR1, (b) does not inhibit or reduce (e.g., prevent)binding of TNFα to TNFR2, (c) does not inhibit or reduce (e.g., prevent)binding of LIGHT to LIGHTR, (d) does not inhibit or reduce (e.g., prevent)binding of LIGHT to LTβR, and / or (e) does not inhibit or reduce (e.g., prevent)binding of FASL to FAS. InAttorney Docket No.62801.72WO01 some embodiments, the TL1A binding protein does not inhibit or reduce (e.g., prevent) binding of TNFα to TNFR1. In some embodiments, the TL1A binding protein does not inhibit or reduce (e.g., prevent) binding of TNFα to TNFR2. In some embodiments, the TL1A binding protein does not inhibit or reduce (e.g., prevent) binding of LIGHT to LIGHTR. In some embodiments, the TL1A binding protein does not inhibit or reduce (e.g., prevent) binding of LIGHT to LTβR. In some embodiments, the TL1A binding protein does not inhibit or reduce (e.g., prevent) binding of FASL to FAS. In some embodiments, the TL1A binding protein (a) does not inhibit or reduce (e.g., prevent) binding of TNFα to TNFR1, (b) does not inhibit or reduce (e.g., prevent) binding of TNFα to TNFR2, (c) does not inhibit or reduce (e.g., prevent) binding of LIGHT to LIGHTR, (d) does not inhibit or reduce (e.g., prevent) binding of LIGHT to LTβR, and (e) does not inhibit or reduce (e.g., prevent) binding of FASL to FAS.

[0186] In some embodiments, the TL1A binding protein exhibits one or more (e.g., 1, 2, 3, 4, and / or 5) of (a) does not specifically bind to TNFα and does not inhibit or reduce (e.g., prevent) binding of TNFα to TNFR1, (b) does not specifically bind to TNFα and does not inhibit or reduce (e.g., prevent) binding of TNFα to TNFR2, (c) does not specifically bind to LIGHT and does not inhibit or reduce (e.g., prevent) binding of LIGHT to LIGHTR, (d) does not specifically bind to LIGHT and does not inhibit or reduce (e.g., prevent) binding of LIGHT to LTβR, and / or (e) does not specifically bind to FASL and does not inhibit or reduce (e.g., prevent) binding of FASL to FAS. In some embodiments, the TL1A binding protein does not specifically bind to TNFα and does not inhibit or reduce (e.g., prevent) binding of TNFα to TNFR1. In some embodiments, the TL1A binding protein does not specifically bind to TNFα and does not inhibit or reduce (e.g., prevent) binding of TNFα to TNFR2. In some embodiments, the TL1A binding protein does not specifically bind to LIGHT and does not inhibit or reduce (e.g., prevent) binding of LIGHT to LIGHTR. In some embodiments, the TL1A binding protein does not specifically bind to LIGHT and does not inhibit or reduce (e.g., prevent) binding of LIGHT to LTβR. In some embodiments, the TL1A binding protein does not specifically bind to FASL and does not inhibit or reduce (e.g., prevent) binding of FASL to FAS. In some embodiments, the TL1A binding protein (a) does not specifically bind to TNFα and does not inhibit or reduce (e.g., prevent) binding of TNFα to TNFR1, (b) does not specifically bind to TNFα and does not inhibit or reduce (e.g., prevent) binding of TNFα to TNFR2, (c) does not specifically bind to LIGHT and does not inhibit or reduce (e.g., prevent) binding of LIGHT to LIGHTR, (d) does not specifically bind to LIGHT and does notAttorney Docket No.62801.72WO01 inhibit or reduce (e.g., prevent) binding of LIGHT to LTβR, and (e) does not specifically bind to FASL and does not inhibit or reduce (e.g., prevent) binding of FASL to FAS.

[0187] In some embodiments, the TL1A binding protein exhibits one or more (e.g., 1, 2, 3, 4, and / or 5) of (a) does not inhibit or reduce (e.g., prevent) binding of hTNFα to hTNFR1, (b) does not inhibit or reduce (e.g., prevent) binding of hTNFα to hTNFR2, (c) does not inhibit or reduce (e.g., prevent) binding of hLIGHT to hLIGHTR, (d) does not inhibit or reduce (e.g., prevent) binding of hLIGHT to hLTβR, and / or (e) does not inhibit or reduce (e.g., prevent) binding of hFASL to hFAS. In some embodiments, the TL1A binding protein does not inhibit or reduce (e.g., prevent) binding of hTNFα to hTNFR1. In some embodiments, the TL1A binding protein does not inhibit or reduce (e.g., prevent) binding of hTNFα to hTNFR2. In some embodiments, the TL1A binding protein does not inhibit or reduce (e.g., prevent) binding of hLIGHT to hLIGHTR. In some embodiments, the TL1A binding protein does not inhibit or reduce (e.g., prevent) binding of hLIGHT to hLTβR. In some embodiments, the TL1A binding protein does not inhibit or reduce (e.g., prevent) binding of FASL to FAS. In some embodiments, the TL1A binding protein (a) does not inhibit or reduce (e.g., prevent) binding of hTNFα to hTNFR1, (b) does not inhibit or reduce (e.g., prevent) binding of hTNFα to hTNFR2, (c) does not inhibit or reduce (e.g., prevent) binding of hLIGHT to hLIGHTR, (d) does not inhibit or reduce (e.g., prevent) binding of hLIGHT to hLTβR, and (e) does not inhibit or reduce (e.g., prevent) binding of hFASL to hFAS.

[0188] In some embodiments, the TL1A binding protein exhibits one or more (e.g., 1, 2, 3, 4, and / or 5) of (a) does not specifically bind to hTNFα and does not inhibit or reduce (e.g., prevent) binding of hTNFα to hTNFR1, (b) does not specifically bind to hTNFα and does not inhibit or reduce (e.g., prevent) binding of hTNFα to hTNFR2, (c) does not specifically bind to hLIGHT and does not inhibit or reduce (e.g., prevent) binding of hLIGHT to hLIGHTR, (d) does not specifically bind to hLIGHT and does not inhibit or reduce (e.g., prevent) binding of hLIGHT to hLTβR, and / or (e) does not specifically bind to hFASL and does not inhibit or reduce (e.g., prevent) binding of hFASL to hFAS. In some embodiments, the TL1A binding protein does not specifically bind to hTNFα and does not inhibit or reduce (e.g., prevent) binding of hTNFα to hTNFR1. In some embodiments, the TL1A binding protein does not specifically bind to hTNFα and does not inhibit or reduce (e.g., prevent) binding of hTNFα to hTNFR2. In some embodiments, the TL1A binding protein does not specifically bind to hLIGHT and does not inhibit or reduce (e.g., prevent) binding of hLIGHT to hLIGHTR. In some embodiments, the TL1A binding protein does not specificallyAttorney Docket No.62801.72WO01 bind to hLIGHT and does not inhibit or reduce (e.g., prevent) binding of hLIGHT to hLTβR. In some embodiments, the TL1A binding protein does not specifically bind to hFASL and does not inhibit or reduce (e.g., prevent) binding of hFASL to hFAS. In some embodiments, the TL1A binding protein (a) does not specifically bind to hTNFα and does not inhibit or reduce (e.g., prevent) binding of hTNFα to hTNFR1, (b) does not specifically bind to hTNFα and does not inhibit or reduce (e.g., prevent) binding of hTNFα to hTNFR2, (c) does not specifically bind to hLIGHT and does not inhibit or reduce (e.g., prevent) binding of hLIGHT to hLIGHTR, (d) does not specifically bind to hLIGHT and does not inhibit or reduce (e.g., prevent) binding of hLIGHT to hLTβR, and (e) does not specifically bind to hFASL and does not inhibit or reduce (e.g., prevent) binding of hFASL to hFAS.

[0189] In some embodiments, the TL1A binding protein specifically binds one or more of TNFα, LIGHT, FASL, and / or TL1A. In some embodiments, the TL1A binding protein specifically binds 2, 3, or 4 of TNFα, LIGHT, FASL, and / or TL1A. In some embodiments, the TL1A binding protein specifically binds TNFα, LIGHT, FASL, and / or TL1A. In some embodiments, the TL1A binding protein specifically binds TNFα, LIGHT, FASL, and TL1A. In some embodiments, the TL1A binding protein specifically binds a plurality of TNFα, LIGHT, FASL, and / or TL1A.

[0190] In some embodiments, the TL1A binding protein specifically binds one or more of hTNFα, hLIGHT, hFASL, and / or hTL1A. In some embodiments, the TL1A binding protein specifically binds 2, 3, or 4 of hTNFα, hLIGHT, hFASL, and / or hTL1A. In some embodiments, the TL1A binding protein specifically binds hTNFα, hLIGHT, hFASL, and / or hTL1A. In some embodiments, the TL1A binding protein specifically binds hTNFα, hLIGHT, hFASL, and hTL1A. In some embodiments, the TL1A binding protein specifically binds a plurality of hTNFα, hLIGHT, hFASL, and / or hTL1A.

[0191] In some embodiments, the TL1A binding protein inhibits or reduces (e.g., prevents) binding of one or more TNFSF ligand (e.g., TNFα, LIGHT, FASL, and / or TL1A) to one or more of the TNFSF ligand’s (e.g., TNFα, LIGHT, FASL, and / or TL1A) cognate receptor.

[0192] In some embodiments, the TL1A binding protein exhibits one or more (e.g., 1, 2, 3, 4, 5, and / or 6) of (a) inhibits or reduces (e.g., prevents) binding of TNFα to TNFR1, (b) inhibits or reduces (e.g., prevents) binding of TNFα to TNFR2, (c) inhibits or reduces (e.g., prevents) binding of LIGHT to LIGHTR, (d) inhibits or reduces (e.g., prevents) binding of LIGHT to LTβR, (e) inhibits or reduces (e.g., prevents) binding of FASL to FAS, and / or (f) inhibits or reduces (e.g.,Attorney Docket No.62801.72WO01 prevents) binding of TL1A to DR3. In some embodiments, the TL1A binding protein inhibits or reduces (e.g., prevents) binding of TNFα to TNFR1. In some embodiments, the TL1A binding protein inhibits or reduces (e.g., prevents) binding of TNFα to TNFR2. In some embodiments, the TL1A binding protein inhibits or reduces (e.g., prevents) binding of LIGHT to LIGHTR. In some embodiments, the TL1A binding protein inhibits or reduces (e.g., prevents) binding of LIGHT to LTβR. In some embodiments, the TL1A binding protein inhibits or reduces (e.g., prevents) binding of FASL to FAS. In some embodiments, the TL1A binding protein inhibits or reduces (e.g., prevents) binding of TL1A to DR3. In some embodiments, the TL1A binding protein (a) inhibits or reduces (e.g., prevents) binding of TNFα to TNFR1, (b) inhibits or reduces (e.g., prevents) binding of TNFα to TNFR2, (c) inhibits or reduces (e.g., prevents) binding of LIGHT to LIGHTR, (d) inhibits or reduces (e.g., prevents) binding of LIGHT to LTβR, (e) inhibits or reduces (e.g., prevents) binding of FASL to FAS, and / or (f) inhibits or reduces (e.g., prevents) binding of TL1A to DR3.

[0193] In some embodiments, the TL1A binding protein exhibits one or more (e.g., 1, 2, 3, 4, 5, and / or 6) of (a) specifically binds to TNFα and inhibits or reduces (e.g., prevents) binding of TNFα to TNFR1, (b) specifically binds to TNFα and inhibits or reduces (e.g., prevents) binding of TNFα to TNFR2, (c) specifically binds to LIGHT and inhibits or reduces (e.g., prevents) binding of LIGHT to LIGHTR, (d) specifically binds to LIGHT and inhibits or reduces (e.g., prevents) binding of LIGHT to LTβR, (e) specifically binds to FASL and inhibits or reduces (e.g., prevents) binding of FASL to FAS, and / or (f) specifically binds to TL1A and inhibits or reduces (e.g., prevents) binding of TL1A to DR3. In some embodiments, the TL1A binding protein specifically binds to TNFα and inhibits or reduces (e.g., prevents) binding of TNFα to TNFR1. In some embodiments, the TL1A binding protein specifically binds to TNFα and inhibits or reduces (e.g., prevents) binding of TNFα to TNFR2. In some embodiments, the TL1A binding protein specifically binds to LIGHT and inhibits or reduces (e.g., prevents) binding of LIGHT to LIGHTR. In some embodiments, the TL1A binding protein specifically binds to LIGHT and inhibits or reduces (e.g., prevents) binding of LIGHT to LTβR. In some embodiments, the TL1A binding protein specifically binds to FASL and inhibits or reduces (e.g., prevents) binding of FASL to FAS. In some embodiments, the TL1A binding protein specifically binds to TL1A and inhibits or reduces (e.g., prevents) binding of TL1A to DR3. In some embodiments, the TL1A binding protein (a) specifically binds to TNFα and inhibits or reduces (e.g., prevents) binding of TNFα to TNFR1,Attorney Docket No.62801.72WO01 (b) specifically binds to TNFα and inhibits or reduces (e.g., prevents) binding of TNFα to TNFR2, (c) specifically binds to LIGHT and inhibits or reduces (e.g., prevents) binding of LIGHT to LIGHTR, (d) specifically binds to LIGHT and inhibits or reduces (e.g., prevents) binding of LIGHT to LTβR, (e) specifically binds to FASL and inhibits or reduces (e.g., prevents) binding of FASL to FAS, and (f) specifically binds to TL1A and inhibits or reduces (e.g., prevents) binding of TL1A to DR3.

[0194] In some embodiments, the TL1A binding protein exhibits one or more (e.g., 1, 2, 3, 4, 5, and / or 6) of (a) inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR1, (b) inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR2, (c) inhibits or reduces (e.g., prevents) binding of hLIGHT to hLIGHTR, (d) inhibits or reduces (e.g., prevents) binding of hLIGHT to hLTβR, (e) inhibits or reduces (e.g., prevents) binding of hFASL to hFAS, and / or (f) inhibits or reduces (e.g., prevents) binding of hTL1A to hDR3. In some embodiments, the TL1A binding protein inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR1. In some embodiments, the TL1A binding protein inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR2. In some embodiments, the TL1A binding protein inhibits or reduces (e.g., prevents) binding of hLIGHT to hLIGHTR. In some embodiments, the TL1A binding protein inhibits or reduces (e.g., prevents) binding of hLIGHT to hLTβR. In some embodiments, the TL1A binding protein inhibits or reduces (e.g., prevents) binding of FASL to FAS. In some embodiments, the TL1A binding protein inhibits or reduces (e.g., prevents) binding of hTL1A to hDR3. In some embodiments, the TL1A binding protein (a) inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR1, (b) inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR2, (c) inhibits or reduces (e.g., prevents) binding of hLIGHT to hLIGHTR, (d) inhibits or reduces (e.g., prevents) binding of hLIGHT to hLTβR, (e) inhibits or reduces (e.g., prevents) binding of hFASL to hFAS, and (f) inhibits or reduces (e.g., prevents) binding of hTL1A to hDR3.

[0195] In some embodiments, the TL1A binding protein exhibits one or more (e.g., 1, 2, 3, 4, 5, and / or 6) of (a) specifically binds to hTNFα and inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR1, (b) specifically binds to hTNFα and inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR2, (c) specifically binds to hLIGHT and inhibits or reduces (e.g., prevents) binding of hLIGHT to hLIGHTR, (d) specifically binds to hLIGHT and inhibits or reduces (e.g., prevents) binding of hLIGHT to hLTβR, (e) specifically binds to hFASL and inhibits or reduces (e.g., prevents) binding of hFASL to hFAS, and / or (f) specifically binds to hTL1A and inhibits orAttorney Docket No.62801.72WO01 reduces (e.g., prevents) binding of hTL1A to hDR3. In some embodiments, the TL1A binding protein specifically binds to hTNFα and inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR1. In some embodiments, the TL1A binding protein specifically binds to hTNFα and inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR2. In some embodiments, the TL1A binding protein specifically binds to hLIGHT and inhibits or reduces (e.g., prevents) binding of hLIGHT to hLIGHTR. In some embodiments, the TL1A binding protein specifically binds to hLIGHT and inhibits or reduces (e.g., prevents) binding of hLIGHT to hLTβR. In some embodiments, the TL1A binding protein specifically binds to hFASL and inhibits or reduces (e.g., prevents) binding of hFASL to hFAS. In some embodiments, the TL1A binding protein specifically binds to hTL1A and inhibits or reduces (e.g., prevents) binding of hTL1A to hDR3. In some embodiments, the TL1A binding protein (a) specifically binds to hTNFα and inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR1, (b) specifically binds to hTNFα and inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR2, (c) specifically binds to hLIGHT and inhibits or reduces (e.g., prevents) binding of hLIGHT to hLIGHTR, (d) specifically binds to hLIGHT and inhibits or reduces (e.g., prevents) binding of hLIGHT to hLTβR, (e) specifically binds to hFASL and inhibits or reduces (e.g., prevents) binding of hFASL to hFAS, and (f) specifically binds to hTL1A and inhibits or reduces (e.g., prevents) binding of hTL1A to hDR3.

[0196] For the sake of clarity, and as further described herein, where an immunoreceptor inhibitory protein described herein specifically binds more than one TNFSF ligand (e.g., specifically binds TNFα, LIGHT, FASL, and TL1A), the binding affinity of the TL1A binding protein for each TNFSF ligand can vary.

[0197] In some embodiments, the TL1A binding protein specifically binds heparan sulfate proteoglycans. In some embodiments, the TL1A binding protein comprises a heparan sulfate proteoglycan binding domain. In some embodiments, the TL1A binding protein does not specifically bind heparan sulfate proteoglycans. In some embodiments, the TL1A binding protein does not comprise a heparan sulfate proteoglycan binding domain. 5.2.1.3 TNFα Binding Proteins

[0198] In some aspects and embodiments, a fusion protein described herein (or a combination regimen described herein) comprises a protein that specifically binds the hTNFα.

[0199] The amino acid sequence of proteins that are capable of specifically binding hTNFα isAttorney Docket No.62801.72WO01 set forth in Table 4 (SEQ ID NOS: 455-464). The amino acid sequence of the mature form of the proteins (i.e., lacking the native signal peptide) is set forth in SEQ ID NOS: 455-459. The amino acid sequence of the immature form of the proteins (i.e., containing the native signal peptide) is set forth in SEQ ID NOS: 460-464.

[0200] The signal peptides have been computationally predicted using standard methods (see, e.g., Teufel 2022). A person of ordinary skill in the art would know how to experimentally identify and / or validate a computationally predicted signal peptide using standard methods known in the art, e.g., expression of a protein from a host cell and sequencing of the intracellular form and the extracellular form of the expressed protein (see, e.g., Zhang 2004). Table 4. The Amino Acid Sequence of TNFα Binding Proteins. Description Amino Acid Sequence SEQ ID NO

[0201] In some aspects and embodiments, the TNFα binding protein comprises an amino acidAttorney Docket No.62801.72WO01 sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein comprises an amino acid sequence at least about 85% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein comprises an amino acid sequence at least about 90% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein comprises an amino acid sequence at least about 95% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein comprises an amino acid sequence at least about 99% identical to the amino acid sequence of a protein set forth in Table 4.

[0202] In some embodiments, the TNFα binding protein comprises an amino acid sequence about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein comprises an amino acid sequence about 85% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein comprises an amino acid sequence about 90% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein comprises an amino acid sequence about 95% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein comprises an amino acid sequence about 99% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein comprises an amino acid sequence about 100% identical to the amino acid sequence of a protein set forth in Table 4.

[0203] In some embodiments, the TNFα binding protein consists of an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein consists of an amino acid sequence at least about 85% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein consists of an amino acid sequence at least about 90% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein consists of an amino acid sequence at least about 95% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein consists of an aminoAttorney Docket No.62801.72WO01 acid sequence at least about 99% identical to the amino acid sequence of a protein set forth in Table 4.

[0204] In some embodiments, the TNFα binding protein consists of an amino acid sequence about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein consists of an amino acid sequence about 85% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein consists of an amino acid sequence about 90% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein consists of an amino acid sequence about 95% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein consists of an amino acid sequence about 99% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, the TNFα binding protein consists of an amino acid sequence about 100% identical to the amino acid sequence of a protein set forth in Table 4.

[0205] In some embodiments, the TNFα binding protein comprises the amino acid sequence of a protein set forth in Table 4, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein comprises the amino acid sequence of a protein set forth in Table 4, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein comprises the amino acid sequence of a protein set forth in Table 4, and further consisting of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein comprises the amino acid sequence of a protein set forth in Table 4, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein comprises the amino acid sequence of a protein set forth in Table 4, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein comprises the amino acid sequence of a protein set forth in Table 4, and further comprising or no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).Attorney Docket No.62801.72WO01

[0206] In some embodiments, the TNFα binding protein consists of the amino acid sequence of a protein set forth in Table 4, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein consists of the amino acid sequence of a protein set forth in Table 4, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein consists of the amino acid sequence of a protein set forth in Table 4, and further consisting of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein consists of the amino acid sequence of a protein set forth in Table 4, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein consists of the amino acid sequence of a protein set forth in Table 4, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein consists of the amino acid sequence of a protein set forth in Table 4, and further comprising or no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0207] In some embodiments, the TNFα binding protein comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein comprises an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein comprises an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein comprises an amino acid sequence at least 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein comprises an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

[0208] In some embodiments, the TNFα binding protein comprises an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In someAttorney Docket No.62801.72WO01 embodiments, the TNFα binding protein comprises an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein comprises an amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein comprises an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein comprises an amino acid sequence 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455- 464. In some embodiments, the TNFα binding protein comprises an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

[0209] In some embodiments, the TNFα binding protein consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein consists of an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein consists of an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein consists of an amino acid sequence at least 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein consists of an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

[0210] In some embodiments, the TNFα binding protein consists of an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein consists of an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein consists of an amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein consists of an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, the TNFα binding protein consists of an amino acid sequence 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455- 464. In some embodiments, the TNFα binding protein consists of an amino acid sequence 100%Attorney Docket No.62801.72WO01 identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

[0211] In some embodiments, the TNFα binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further comprising or consists of no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0212] In some embodiments, the TNFα binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the TNFα binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further consisting of no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).Attorney Docket No.62801.72WO01

[0213] In some aspects and embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least about 85% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least about 90% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least about 95% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least about 99% identical to the amino acid sequence of a protein set forth in Table 4.

[0214] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence about 85% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein ((or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence about 90% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence about 95% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment,Attorney Docket No.62801.72WO01 functional variant, or functional fragment / variant thereof) comprising an amino acid sequence about 99% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence about 100% identical to the amino acid sequence of a protein set forth in Table 4.

[0215] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least about 85% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least about 90% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least about 95% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least about 99% identical to the amino acid sequence of a protein set forth in Table 4.

[0216] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence about 85% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence about 90% identical to the amino acid sequence of a protein set forth in Table 4. In someAttorney Docket No.62801.72WO01 embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence about 95% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence about 99% identical to the amino acid sequence of a protein set forth in Table 4. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence about 100% identical to the amino acid sequence of a protein set forth in Table 4.

[0217] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 4, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 4, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 4, and further consisting of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 4, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 4, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 4, and further comprising or noAttorney Docket No.62801.72WO01 more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0218] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 4, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 4, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 4, and further consisting of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 4, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 4, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 4, and further comprising or no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0219] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or aAttorney Docket No.62801.72WO01 functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

[0220] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ IDAttorney Docket No.62801.72WO01 NOS: 455-464.

[0221] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

[0222] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ IDAttorney Docket No.62801.72WO01 NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

[0223] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further comprising or consists of no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0224] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further comprising 1 orAttorney Docket No.62801.72WO01 more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 455-464, and further consisting of no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). (i) Exemplary Properties of TNFα Binding Proteins

[0225] In some embodiments, the TNFα binding proteins described herein are immunosuppressive (e.g., when administered to a subject). In some embodiments, the TNFα binding proteins described herein are anti-inflammatory (e.g., when administered to a subject). In some embodiments, the TNFα binding proteins described herein suppress pro-inflammatory response (e.g., when administered to a subject).

[0226] In some embodiments, the TNFα binding protein is capable of specifically binding TNFα. In some embodiments, the TNFα binding protein is capable of inhibiting or reducing (e.g., preventing) binding of hTNFα to hTNFR1 and / or hTNFR2.

[0227] In some embodiments, the TNFα binding proteins described herein bind a subset (e.g., one or more) TNFSF ligand. In some embodiments, the TNFα binding protein specifically binds TNFα. In some embodiments, the TNFα binding protein specifically binds hTNFα. In some embodiments, the TNFα binding protein can act as a decoy receptor for a TNFSF ligand describedAttorney Docket No.62801.72WO01 herein. In some embodiments, the TNFα binding protein inhibits or reduces (e.g., prevents) binding of TNFα to TNFR1. In some embodiments, the TNFα binding protein specifically binds to TNFα and inhibits or reduces (e.g., prevents) binding of TNFα to TNFR1. In some embodiments, the TNFα binding protein inhibits binding of hTNFα to hTNFR1. In some embodiments, the TNFα binding protein specifically binds to hTNFα and inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR1. In some embodiments, the TNFα binding protein inhibits or reduces (e.g., prevents) binding of TNFα to TNFR2. In some embodiments, the TNFα binding protein specifically binds to TNFα and inhibits or reduces (e.g., prevents) binding of TNFα to TNFR2. In some embodiments, the TNFα binding protein inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR2. In some embodiments, the TNFα binding protein specifically binds to hTNFα and inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR2. In some embodiments, the TNFα binding protein inhibits or reduces (e.g., prevents) binding of TNFα to TNFR1 and TNFR2. In some embodiments, the TNFα binding protein specifically binds to TNFα and inhibits or reduces (e.g., prevents) binding of TNFα to TNFR1 and TNFR2. In some embodiments, the TNFα binding protein inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR1 and TNFR2. In some embodiments, the TNFα binding protein specifically binds to hTNFα and inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR1 and TNFR2. In some embodiments, the TNFα binding protein inhibits NF-κB signaling mediated by binding of hTNFα to hTNFR1. In some embodiments, the TNFα binding protein inhibits NF-κB signaling mediated by binding of hTNFα to hTNFR2.

[0228] In some embodiments, the TNFα binding protein specifically binds LTα. In some embodiments, the TNFα binding protein specifically binds hLTα. In some embodiments, the TNFα binding protein inhibits or reduces (e.g., prevents) binding of LTα to TNFR1. In some embodiments, the TNFα binding protein specifically binds to LTα and inhibits or reduces (e.g., prevents) binding of LTα to TNFR1. In some embodiments, the TNFα binding protein inhibits or reduces (e.g., prevents) binding of hLTα to hTNFR1. In some embodiments, the TNFα binding protein specifically binds to hLTα and inhibits or reduces (e.g., prevents) binding of hLTα to hTNFR1. In some embodiments, the TNFα binding protein inhibits or reduces (e.g., prevents) binding of LTα to TNFR2. In some embodiments, the TNFα binding protein specifically binds to LTα and inhibits or reduces (e.g., prevents) binding of LTα to TNFR2. In some embodiments, the TNFα binding protein inhibits or reduces (e.g., prevents) binding of hLTα to hTNFR2. In someAttorney Docket No.62801.72WO01 embodiments, the TNFα binding protein specifically binds to hLTα and inhibits or reduces (e.g., prevents) binding of hLTα to hTNFR2. In some embodiments, the TNFα binding protein inhibits or reduces (e.g., prevents) binding of LTα to TNFR1 and TNFR2. In some embodiments, the TNFα binding protein specifically binds to LTα and inhibits or reduces (e.g., prevents) binding of LTα to TNFR1 and TNFR2. In some embodiments, the TNFα binding protein inhibits or reduces (e.g., prevents) binding of hLTα to hTNFR1 and TNFR2. In some embodiments, the TNFα binding protein specifically binds to hLTα and inhibits or reduces (e.g., prevents) binding of hLTα to hTNFR1 and TNFR2. In some embodiments, the TNFα binding protein inhibits or reduces (e.g., prevents) NF-κB signaling mediated by binding of hLTα to hTNFR1. In some embodiments, the TNFα binding protein inhibits or reduces (e.g., prevents) NF-κB signaling mediated by binding of hLTα to hTNFR2. 5.2.1.4 CD30 Ligand Binding Proteins

[0229] In some aspects and embodiments, a fusion protein described herein (or a combination regimen described herein) comprises a protein that specifically binds the hCD30L.

[0230] The amino acid sequence of proteins capable of specifically binding hCD30L is set forth in Table 5 (SEQ ID NOS: 465-576). The amino acid sequence of the mature form of the proteins (i.e., lacking the native signal peptide) is set forth in SEQ ID NOS: 465-522. The amino acid sequence of the immature form of the proteins (i.e., containing the native signal peptide) is set forth in SEQ ID NOS: 523-576.

[0231] The signal peptides have been computationally predicted using standard methods (see, e.g., Teufel 2022). A person of ordinary skill in the art would know how to experimentally identify and / or validate a computationally predicted signal peptide using standard methods known in the art, e.g., expression of a protein from a host cell and sequencing of the intracellular form and the extracellular form of the expressed protein (see, e.g., Zhang 2004). Table 5. The Amino Acid Sequence of CD30L Targeting Proteins. Description Amino Acid Sequence SEQ IDAttorney Docket No.62801.72WO01 IMP-217 KTCPADYYLNPENGLCTACVTCLSNMVEIQPCGPDKPRKCECGSGF without native signal KCTLPAVNSCARCTPDTTTKKVQKEQKEQCCNTPDNTKLCYHKYSS467e tideAttorney Docket No.62801.72WO01 without native signal peptide IMP-234 TCPNDYYLEPEDGLCTACVTCLSNMVEIQPCGPNKPRKCQCGPGLKAttorney Docket No.62801.72WO01 IMP-250 EVKLGNQCCPPCGSGQKVTKVCTENSGITCTLCPNGTYLTGLYNCT without native signal NCTQCNDTQITVRNCTSTNNTICASKNHTLFSTPGVQHHKQRQQNH 500 e tide TAHVTVKQAttorney Docket No.62801.72WO01 without native signal RQQNHTAHITVKQGKSGRHTLA peptide IMP-267 IPTSSLPHAPVNGACDEGEYLDKRHNQCCNRCPPGEFAKVRCNGNDAttorney Docket No.62801.72WO01 with native signal TIKKIKPTDQCCTTPDNTKLCYHK peptide IMP-222 MKMNTIFL AIVT LVYT F KT PNDYYLEPED L TA VTAttorney Docket No.62801.72WO01 IMP-240 MNTIFLSAIVTCIVYTTFGKTCPADYYLEPEDGLCTACVTCL with native signal SNMVEIQPCGPDKPRKCQCGPGLKCTVPAVNSCARCTPDTTT 545 e tideAttorney Docket No.62801.72WO01 with native signal YASRLCDSKTNTQCTPCGSGTFTSRNNHLPARLSCNGRRDRVTRLT peptide IESVDALPDIIVFSKDHPDARHVFPKQNV IMP-258 MKSVLYLYILFLSCIIINGRDIAPHAPSDGKCKDNEYKRHNLCPGTAttorney Docket No.62801.72WO01 with native signal CRKCPTGSFDKVKCTGTQNSKCSCLPGWYCATDSSQTEDCRDCIPK peptide RRCPCGYFGGIDEQGNPICKSCCVGEYCDYLRNYRLDPFPPCKLSK CNino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein comprises an amino acid sequence at least about 85% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein comprises an amino acid sequence at least about 90% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein comprises an amino acid sequence at least about 95% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein comprises an amino acid sequence at least about 99% identical to the amino acid sequence of a protein set forth in Table 5.

[0233] In some embodiments, the CD30L binding protein comprises an amino acid sequence about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein comprises an amino acid sequence about 85% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein comprises an amino acid sequence about 90% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein comprises an amino acid sequence about 95% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein comprises an amino acid sequence about 99% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein comprises an amino acid sequence about 100% identical to the amino acid sequence of a protein set forth in Table 5.

[0234] In some embodiments, the CD30L binding protein consists of an amino acid sequenceAttorney Docket No.62801.72WO01 at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein consists of an amino acid sequence at least about 85% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein consists of an amino acid sequence at least about 90% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein consists of an amino acid sequence at least about 95% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein consists of an amino acid sequence at least about 99% identical to the amino acid sequence of a protein set forth in Table 5.

[0235] In some embodiments, the CD30L binding protein consists of an amino acid sequence about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein consists of an amino acid sequence about 85% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein consists of an amino acid sequence about 90% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein consists of an amino acid sequence about 95% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein consists of an amino acid sequence about 99% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, the CD30L binding protein consists of an amino acid sequence about 100% identical to the amino acid sequence of a protein set forth in Table 5.

[0236] In some embodiments, the CD30L binding protein comprises the amino acid sequence of a protein set forth in Table 5, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein comprises the amino acid sequence of a protein set forth in Table 5, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein comprises the amino acid sequence of a protein set forth in Table 5, and further consisting of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding proteinAttorney Docket No.62801.72WO01 comprises the amino acid sequence of a protein set forth in Table 5, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein comprises the amino acid sequence of a protein set forth in Table 5, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein comprises the amino acid sequence of a protein set forth in Table 5, and further comprising or no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0237] In some embodiments, the CD30L binding protein consists of the amino acid sequence of a protein set forth in Table 5, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein consists of the amino acid sequence of a protein set forth in Table 5, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein consists of the amino acid sequence of a protein set forth in Table 5, and further consisting of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein consists of the amino acid sequence of a protein set forth in Table 5, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein consists of the amino acid sequence of a protein set forth in Table 5, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein consists of the amino acid sequence of a protein set forth in Table 5, and further comprising or no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0238] In some embodiments, the CD30L binding protein comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein comprises an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein comprises an amino acid sequence at least 90% identical to the aminoAttorney Docket No.62801.72WO01 acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein comprises an amino acid sequence at least 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein comprises an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576.

[0239] In some embodiments, the CD30L binding protein comprises an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein comprises an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein comprises an amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein comprises an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein comprises an amino acid sequence 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein comprises an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465- 576.

[0240] In some embodiments, the CD30L binding protein consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein consists of an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein consists of an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein consists of an amino acid sequence at least 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein consists of an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576.

[0241] In some embodiments, the CD30L binding protein consists of an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%Attorney Docket No.62801.72WO01 identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein consists of an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein consists of an amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein consists of an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein consists of an amino acid sequence 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, the CD30L binding protein consists of an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465- 576.

[0242] In some embodiments, the CD30L binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further comprising or consists of no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0243] In some embodiments, the CD30L binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further comprising at least about 1,Attorney Docket No.62801.72WO01 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, the CD30L binding protein consists of the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further consisting of no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0244] In some aspects and embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least about 85% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least about 90% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least about 95% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least about 99% identical to the amino acid sequence of a protein set forth in Table 5.

[0245] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 5. InAttorney Docket No.62801.72WO01 some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence about 85% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein ((or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence about 90% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence about 95% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence about 99% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence about 100% identical to the amino acid sequence of a protein set forth in Table 5.

[0246] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least about 85% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least about 90% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least about 95% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least about 99% identical to the amino acid sequence of a protein set forth in Table 5.Attorney Docket No.62801.72WO01

[0247] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence about 85% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence about 90% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence about 95% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence about 99% identical to the amino acid sequence of a protein set forth in Table 5. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence about 100% identical to the amino acid sequence of a protein set forth in Table 5.

[0248] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 5, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 5, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 5, and further consisting of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In someAttorney Docket No.62801.72WO01 embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 5, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 5, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence of a protein set forth in Table 5, and further comprising or no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0249] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 5, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 5, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 5, and further consisting of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 5, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 5, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g.,Attorney Docket No.62801.72WO01 substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence of a protein set forth in Table 5, and further comprising or no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0250] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576.

[0251] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising anAttorney Docket No.62801.72WO01 amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576.

[0252] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence at least 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576.

[0253] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,Attorney Docket No.62801.72WO01 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 85% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 90% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 99% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576. In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of an amino acid sequence 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576.

[0254] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof)Attorney Docket No.62801.72WO01 comprising the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) comprising the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further comprising or consists of no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.).

[0255] In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further comprising 1 or more but less than 15% (less than 12%, less than 10%, less than 8%), amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further comprising at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further comprising about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further consisting of about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). In some embodiments, a fusion protein described herein comprises a protein (or a functional fragment, functional variant, or functional fragment / variant thereof) consisting of the amino acid sequence set forth in any one of SEQ ID NOS: 465-576, and further consisting of no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations (e.g., substitutions, additions, deletions, etc.). (i) Exemplary Properties of CD30L Binding Proteins

[0256] In some embodiments, the CD30L binding proteins described herein are immunosuppressive (e.g., when administered to a subject). In some embodiments, the CD30LAttorney Docket No.62801.72WO01 binding proteins described herein are anti-inflammatory (e.g., when administered to a subject). In some embodiments, the CD30L binding proteins described herein suppress pro-inflammatory response (e.g., when administered to a subject).

[0257] In some embodiments, the CD30L binding protein is capable of specifically binding CD30L. In some embodiments, the CD30L binding protein is capable of inhibiting or reducing (e.g., preventing) binding of hCD30L to hCD30.

[0258] In some embodiments, the CD30L binding proteins described herein bind a subset (e.g., one or more) TNFSF ligand. In some embodiments, the CD30L binding protein specifically binds CD30L. In some embodiments, the CD30L binding protein specifically binds hCD30L.

[0259] In some embodiments, the CD30L binding protein specifically binds CD30L expressed on the surface of an immune cell. In some embodiments, the CD30L binding protein specifically binds CD30L expressed on the surface of an activated immune cell. In some embodiments, the CD30L binding protein specifically binds hCD30L expressed on the surface of an activated immune cell.

[0260] In some embodiments, the CD30L binding protein can act as a decoy receptor for a TNFSF ligand described herein (e.g., CD30L). In some embodiments, the CD30L binding protein inhibits or reduces (e.g., prevents) binding of CD30L to CD30. In some embodiments, the CD30L binding protein specifically binds to CD30L and inhibits binding of CD30L to CD30. In some embodiments, the CD30L binding protein inhibits or reduces (e.g., prevents) binding of hCD30L to hCD30. In some embodiments, the CD30L binding protein specifically binds to hCD30 and inhibits or reduces (e.g., prevents) binding of hCD30 to hCD30L. 5.2.2 Integrin Targeting Immunomodulatory Fusion Proteins

[0261] The present disclosure provides, inter alia, fusion proteins (e.g., immunomodulatory fusion proteins (IFPs)) (and functional fragments and variants thereof) that e.g., comprise one or more integrin binding domain (e.g., described herein) and one or more immunomodulatory protein (e.g., described herein). Integrin binding domains include, those, e.g., described herein, see, e.g., § 5.2.2.1. Immunomodulatory proteins described herein include, e.g., those described in §§ 5.2.1.1, 5.2.1.2, 5.2.1.3, and 5.2.1.4. Immunomodulatory proteins described herein include, e.g., those that specifically bind to IL-10 (e.g., human IL-10)) (see, e.g., § 5.2.1.1),those that specifically bind to TL1A (e.g., human TL1A)) (see, e.g., § 5.2.1.2), those that specifically bind to TNFα (e.g., humanAttorney Docket No.62801.72WO01 TNFα)) (see, e.g., § 5.2.1.3), and those that specifically bind to CD30L (e.g., human CD30L)) (see, e.g., § 5.2.1.4).

[0262] The amino acid sequence of various reference human proteins referred to throughout the instant disclosure is set forth Table 6 below. Table 6. The Amino Acid Sequence of Human Reference Proteins. Description Amino Acid Sequence SEQ ID NOAttorney Docket No.62801.72WO01 VNPTSFVYGSNDENEPETCMVEKMNLTFHVINTGNSMAPNVSVE IMVPNSFSPQTDKLFNILDVQTTTGECHFENYQRVCALEQQKSA MQTLKGIVRFLSKTDKRLLYCIKADPHCLNFLCNFGKMESGKEAAttorney Docket No.62801.72WO01 GSSKPAGDQLPAALWTSSAVLGLLLLALPTYHLWKRCRHLAEDD THPPASLRLLPQVSAWAGLRGTGQVGISPS QSLQVKPLQVEPPEPVVAVALGASRQLTCRLACADRGASVQWRG5.2.2.1 Integrin Binding Domains

[0263] As described above, fusion proteins described herein comprise one or more integrin binding domain.

[0264] Integrins are a family of ubiquitous αβ heterodimeric receptors that exist in multiple conformations and interact with a diverse group of ligands. These molecules, inter alia, mediate interactions between cells and cells with the extracellular matrix (ECM) and thereby, e.g., serve a role in signaling and homeostasis. By facilitating dynamic linkages between the intracellular actin cytoskeleton and the ECM, integrins also transduce both external and internal mechanochemical cues and bi-directional signaling across the plasma membrane. In mammals, the family of integrins is comprised of about 24 αβ pairs of heterodimeric transmembrane adhesion receptors and cell- surface proteins. These pairings are known to involve about 18 α and about 8 β subunits. The αβ pairings of integrin subunits dictate the specificity of the integrin to a particular ligand, modulate formation of intracellular adhesion complexes, and regulate downstream signaling. See, e.g., Mezu-Ndubuisi OJ, Maheshwari A. The role of integrins in inflammation and angiogenesis. Pediatr Res. 2021 May;89(7):1619-1626. doi: 10.1038 / s41390-020-01177-9. Epub 2020 Oct 7. PMID: 33027803; PMCID: PMC8249239; Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Integrins. Available from: https: / / www.ncbi.nlm.nih.gov / books / NBK26867 / ; Danen EHJ. Integrins: An Overview of Structural and Functional Aspects. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013. Available from: https: / / www.ncbi.nlm.nih.gov / books / NBK6259 / ; the entire contents of each of which are incorporated herein by reference for all purposes.

[0265] In some embodiments, the integrin binding domain specifically binds a plurality of integrins. In some embodiments, the integrin binding domain selectively binds one or moreAttorney Docket No.62801.72WO01 integrin but not others. In some embodiments, the integrin binding domain specifically binds one or more integrin expressed on surface of one or more immune cell (e.g., T cells).

[0266] In some embodiments, the integrin binding domain specifically binds any one or more of α1β1, α2β1, α10β1, α11β1, α5β1, α8β1, α5β1, α5β3, α5β5, α5β6, α5β8, αIIbβ3, α3β1, α6β1, α7β1, α6β4, α4β1, α9β1, α4β7, αEβ7, αLβ2, αMβ2, αXβ2, and / or αDβ2. In some embodiments, the integrin binding domain specifically binds any one or more of α1β1, α2β1, α10β1, and / or α11β1. In some embodiments, the integrin binding domain specifically binds any one or more of α5β1, α8β1, α5β1, α5β3, α5β5, α5β6, α5β8, and / or αIIbβ3. In some embodiments, the integrin binding domain specifically binds any one or more of α3β1, α6β1, α7β1, and / or α6β4. In some embodiments, the integrin binding domain specifically binds any one or more of α4β1 and / or α9β1. In some embodiments, the integrin binding domain specifically binds any one or more of α4β7, αEβ7, αLβ2, αMβ2, αXβ2, and / or αDβ2.

[0267] In some preferred embodiments, the integrin binding domain specifically α4β7 integrin.

[0268] In some embodiments, the integrin binding domain comprises an antibody. Exemplary antibodies include, full-length antibodies, scFvs, Fabs, single domain antibodies (e.g., VHH), scFv-Fc, Fab-Fc, and single domain antibody-Fc (e.g., VHH-Fc).

[0269] In some embodiments, the integrin binding domain comprises a scFv. In some embodiments, the integrin binding domain comprises a Fab. In some embodiments, the integrin binding domain comprises a full-length antibody. In some embodiments, the integrin binding domain comprises a single domain antibody. In some embodiments, the integrin binding domain comprises a VHH. In some embodiments, the integrin binding domain comprises a scFv-Fc. In some embodiments, the integrin binding domain comprises a Fab-Fc. In some embodiments, the integrin binding domain comprises a (scFv)2-Fc. In some embodiments, the integrin binding domain comprises a (Fab)2-Fc.

[0270] In some embodiments, the integrin binding domain comprises an antibody mimetic (e.g., described herein). For example, a 10th type III domain of fibronectin (e.g., AdNectins®) or designed ankyrin repeat proteins (e.g., DARPins®).

[0271] Exemplary antibody-based integrin binding domains that specifically bind α4β7 integrin include those described in, e.g., US10004808B2, US10918716B2, US11884731B2, and US9663579B2, the entire contents of each of which is incorporated herein by reference for allAttorney Docket No.62801.72WO01 purposes.

[0272] The amino acid sequence of exemplary α4β7 integrin binding domains that can be utilized in the fusion proteins described herein is provided in Table 2. The CDRs set forth in Table 7, are denoted according to Kabat. A person of ordinary skill in the art would be able to determine the CDRs as defined by another scheme, e.g., Chothia, IMGT, using ordinary methods known in the art. Table 7. The Amino Acid Sequence of Exemplary α4β7 Integrin Binding Domains. Description SEQ ID NO Amino Acid Sequence CDR-H1 583SYWMHH L D N S Q H L D S P P F N Q P W R N S Q L D V

[0273] In some embodiments, the integrin (e.g., α4β7 integrin) binding domain comprises an integrin (e.g., α4β7 integrin) binding domain provided in Table 7. In some embodiments, theAttorney Docket No.62801.72WO01 integrin (e.g., α4β7 integrin) binding domain comprises a VH that comprises: a CDR-H1, a CDR- H2, and a CDR-H3; and VL comprises CDR-L1, a CDR-L2, and a CDR-L3. In some embodiments, the integrin (e.g., α4β7 integrin) binding domain comprises a VH that comprises: a CDR-H1, a CDR-H2, and a CDR-H3 set forth in Table 7; and VL comprises CDR-L1, a CDR-L2, and a CDR-L3 set forth in Table 7.

[0274] In some embodiments, the amino acid sequence of CDR-H1 comprises or consists of the amino acid sequence of a CDR-H1 of a VH set forth in Table 7, or the amino acid sequence of a CDR-H1 of a VH set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H2 comprises or consists of the amino acid sequence of a CDR-H2 of a VH set forth in Table 7, or the amino acid sequence of a CDR-H2 of a VH set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H3 comprises or consists of the amino acid sequence of a CDR-H3 of a VH set forth in Table 7, or the amino acid sequence of a CDR-H3 of a VH set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L1 comprises or consists of the amino acid sequence of a CDR-L1 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L1 of a VL set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L2 comprises or consists of the amino acid sequence of a CDR-L2 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L2 of a VL set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of CDR-L3 comprises or consists of the amino acid sequence of a CDR-L3 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L3 of a VL set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0275] In some embodiments, the amino acid sequence of CDR-H1 comprises or consists of the amino acid sequence of a CDR-H1 set forth in Table 7, or the amino acid sequence of a CDR- H1 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H2 comprises or consists of the amino acid sequence of a CDR-H2 set forth in Table 7, or the amino acid sequence of a CDR-H2 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g.,Attorney Docket No.62801.72WO01 substitution, deletion, addition, etc.); the amino acid sequence of CDR-H3 comprises or consists of the amino acid sequence of a CDR-H3 set forth in Table 7, or the amino acid sequence of a CDR-H3 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L1 comprises or consists of the amino acid sequence of a CDR-L1 set forth in Table 7, or the amino acid sequence CDR1 of a VL set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L2 comprises or consists of the amino acid sequence of a CDR-L2 set forth in Table 7, or the amino acid sequence of a CDR-L2 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of CDR-L3 comprises or consists of the amino acid sequence of a CDR-L3 set forth in Table 7, or the amino acid sequence of a CDR-L3 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0276] In some embodiments, the amino acid sequence of CDR-H1 comprises the amino acid sequence of a CDR-H1 of a VH set forth in Table 7, or the amino acid sequence of a CDR-H1 of a VH set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H2 comprises the amino acid sequence of a CDR-H2 of a VH set forth in Table 7, or the amino acid sequence of a CDR- H2 of a VH set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H3 comprises the amino acid sequence of a CDR-H3 of a VH set forth in Table 7, or the amino acid sequence of a CDR- H3 of a VH set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L1 comprises the amino acid sequence of a CDR-L1 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L1 of a VL set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L2 comprises the amino acid sequence of a CDR-L2 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L2 of a VL set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of CDR-L3 comprises the amino acid sequence of a CDR-L3 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L3 of a VL set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g.,Attorney Docket No.62801.72WO01 substitution, deletion, addition, etc.).

[0277] In some embodiments, the amino acid sequence of CDR-H1 comprises the amino acid sequence of a CDR-H1 set forth in Table 7, or the amino acid sequence of a CDR-H1 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H2 comprises the amino acid sequence of a CDR- H2 set forth in Table 7, or the amino acid sequence of a CDR-H2 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H3 comprises the amino acid sequence of a CDR-H3 set forth in Table 7, or the amino acid sequence of a CDR-H3 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L1 comprises the amino acid sequence of a CDR-L1 set forth in Table 7, or the amino acid sequence CDR1 of a VL set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L2 comprises the amino acid sequence of a CDR-L2 set forth in Table 7, or the amino acid sequence of a CDR-L2 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of CDR-L3 comprises the amino acid sequence of a CDR-L3 set forth in Table 7, or the amino acid sequence of a CDR-L3 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0278] In some embodiments, the amino acid sequence of CDR-H1 comprises the amino acid sequence of a CDR-H1 of a VH set forth in Table 7, or the amino acid sequence of a CDR-H1 of a VH set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H2 comprises the amino acid sequence of a CDR- H2 of a VH set forth in Table 7, or the amino acid sequence of a CDR-H2 of a VH set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H3 comprises the amino acid sequence of a CDR-H3 of a VH set forth in Table 7, or the amino acid sequence of a CDR-H3 of a VH set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L1 comprises the amino acid sequence of a CDR-L1 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L1 of a VL set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-Attorney Docket No.62801.72WO01 L2 comprises the amino acid sequence of a CDR-L2 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L2 of a VL set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of CDR-L3 comprises the amino acid sequence of a CDR-L3 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L3 of a VL set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0279] In some embodiments, the amino acid sequence of CDR-H1 comprises the amino acid sequence of a CDR-H1 set forth in Table 7, or the amino acid sequence of a CDR-H1 set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H2 comprises the amino acid sequence of a CDR-H2 set forth in Table 7, or the amino acid sequence of a CDR-H2 set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H3 comprises the amino acid sequence of a CDR-H3 set forth in Table 7, or the amino acid sequence of a CDR-H3 set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L1 comprises the amino acid sequence of a CDR-L1 set forth in Table 7, or the amino acid sequence CDR1 of a VL set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L2 comprises the amino acid sequence of a CDR-L2 set forth in Table 7, or the amino acid sequence of a CDR-L2 set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of CDR-L3 comprises the amino acid sequence of a CDR-L3 set forth in Table 7, or the amino acid sequence of a CDR-L3 set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0280] In some embodiments, the amino acid sequence of CDR-H1 comprises the amino acid sequence of a CDR-H1 of a VH set forth in Table 7; the amino acid sequence of CDR-H2 comprises the amino acid sequence of a CDR-H2 of a VH set forth in Table 7; the amino acid sequence of CDR-H3 comprises the amino acid sequence of a CDR-H3 of a VH set forth in Table 7; the amino acid sequence of CDR-L1 comprises the amino acid sequence of a CDR-L1 of a VL set forth in Table 7; the amino acid sequence of CDR-L2 comprises the amino acid sequence of a CDR-L2 of a VL set forth in Table 7; and the amino acid sequence of CDR-L3 comprises the amino acid sequence of a CDR-L3 of a VL set forth in Table 7.Attorney Docket No.62801.72WO01

[0281] In some embodiments, the amino acid sequence of CDR-H1 comprises the amino acid sequence of a CDR-H1 set forth in Table 7; the amino acid sequence of CDR-H2 comprises the amino acid sequence of a CDR-H2 set forth in Table 7; the amino acid sequence of CDR-H3 comprises the amino acid sequence of a CDR-H3 set forth in Table 7; the amino acid sequence of CDR-L1 comprises the amino acid sequence of a CDR-L1 set forth in Table 7; the amino acid sequence of CDR-L2 comprises the amino acid sequence of a CDR-L2 set forth in Table 7; and the amino acid sequence of CDR-L3 comprises the amino acid sequence of a CDR-L3 set forth in Table 7.

[0282] In some embodiments, the amino acid sequence of CDR-H1 consists of the amino acid sequence of a CDR-H1 of a VH set forth in Table 7, or the amino acid sequence of a CDR-H1 of a VH set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H2 consists of the amino acid sequence of a CDR-H2 of a VH set forth in Table 7, or the amino acid sequence of a CDR- H2 of a VH set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H3 consists of the amino acid sequence of a CDR-H3 of a VH set forth in Table 7, or the amino acid sequence of a CDR- H3 of a VH set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L1 consists of the amino acid sequence of a CDR-L1 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L1 of a VL set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L2 consists of the amino acid sequence of a CDR-L2 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L2 of a VL set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of CDR-L3 consists of the amino acid sequence of a CDR-L3 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L3 of a VL set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0283] In some embodiments, the amino acid sequence of CDR-H1 consists of the amino acid sequence of a CDR-H1 set forth in Table 7, or the amino acid sequence of a CDR-H1 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H2 consists of the amino acid sequence of a CDR-Attorney Docket No.62801.72WO01 H2 set forth in Table 7, or the amino acid sequence of a CDR-H2 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H3 consists of the amino acid sequence of a CDR-H3 set forth in Table 7, or the amino acid sequence of a CDR-H3 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L1 consists of the amino acid sequence of a CDR-L1 set forth in Table 7, or the amino acid sequence CDR1 of a VL set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L2 consists of the amino acid sequence of a CDR-L2 set forth in Table 7, or the amino acid sequence of a CDR-L2 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of CDR-L3 consists of the amino acid sequence of a CDR-L3 set forth in Table 7, or the amino acid sequence of a CDR-L3 set forth in Table 7 comprising or consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0284] In some embodiments, the amino acid sequence of CDR-H1 consists of the amino acid sequence of a CDR-H1 of a VH set forth in Table 7, or the amino acid sequence of a CDR-H1 of a VH set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H2 consists of the amino acid sequence of a CDR- H2 of a VH set forth in Table 7, or the amino acid sequence of a CDR-H2 of a VH set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H3 consists of the amino acid sequence of a CDR-H3 of a VH set forth in Table 7, or the amino acid sequence of a CDR-H3 of a VH set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L1 consists of the amino acid sequence of a CDR-L1 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L1 of a VL set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR- L2 consists of the amino acid sequence of a CDR-L2 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L2 of a VL set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of CDR-L3 consists of the amino acid sequence of a CDR-L3 of a VL set forth in Table 7, or the amino acid sequence of a CDR-L3 of a VL set forth in Table 7 consisting of 1, 2, or 3 amino acid variationsAttorney Docket No.62801.72WO01 (e.g., substitution, deletion, addition, etc.).

[0285] In some embodiments, the amino acid sequence of CDR-H1 consists of the amino acid sequence of a CDR-H1 set forth in Table 7, or the amino acid sequence of a CDR-H1 set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H2 consists of the amino acid sequence of a CDR-H2 set forth in Table 7, or the amino acid sequence of a CDR-H2 set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR- H3 consists of the amino acid sequence of a CDR-H3 set forth in Table 7, or the amino acid sequence of a CDR-H3 set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L1 consists of the amino acid sequence of a CDR-L1 set forth in Table 7, or the amino acid sequence CDR1 of a VL set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L2 consists of the amino acid sequence of a CDR-L2 set forth in Table 7, or the amino acid sequence of a CDR-L2 set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of CDR-L3 consists of the amino acid sequence of a CDR-L3 set forth in Table 7, or the amino acid sequence of a CDR-L3 set forth in Table 7 consisting of 1, 2, or 3 amino acid variations (e.g., substitution, deletion, addition, etc.).

[0286] In some embodiments, the amino acid sequence of CDR-H1 consists of the amino acid sequence of a CDR-H1 of a VH set forth in Table 7; the amino acid sequence of CDR-H2 consists of the amino acid sequence of a CDR-H2 of a VH set forth in Table 7; the amino acid sequence of CDR-H3 consists of the amino acid sequence of a CDR-H3 of a VH set forth in Table 7; the amino acid sequence of CDR-L1 consists of the amino acid sequence of a CDR-L1 of a VL set forth in Table 7; the amino acid sequence of CDR-L2 consists of the amino acid sequence of a CDR-L2 of a VL set forth in Table 7; and the amino acid sequence of CDR-L3 consists of the amino acid sequence of a CDR-L3 of a VL set forth in Table 7.

[0287] In some embodiments, the amino acid sequence of CDR-H1 consists of the amino acid sequence of a CDR-H1 set forth in Table 7; the amino acid sequence of CDR-H2 consists of the amino acid sequence of a CDR-H2 set forth in Table 7; the amino acid sequence of CDR-H3 consists of the amino acid sequence of a CDR-H3 set forth in Table 7; the amino acid sequence of CDR-L1 consists of the amino acid sequence of a CDR-L1 set forth in Table 7; the amino acidAttorney Docket No.62801.72WO01 sequence of CDR-L2 consists of the amino acid sequence of a CDR-L2 set forth in Table 7; and the amino acid sequence of CDR-L3 consists of the amino acid sequence of a CDR-L3 set forth in Table 7.

[0288] In some embodiments, the amino acid sequence of the VH comprises or consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 7. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 7. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 7. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence 100% identical to the amino acid sequence of a VH set forth in Table 7. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 7. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 7. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence 100% identical to the amino acid sequence of a VH set forth in Table 7.

[0289] In some embodiments, the amino acid sequence of the VL comprises or consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 7. In some embodiments, the amino acid sequence of the VL comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 7. In some embodiments, the amino acid sequence of the VL comprises an amino acid sequence at 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 7. In some embodiments, the amino acid sequence of the VL comprises an amino acid sequence 100% identical to the amino acid sequence of a VL set forth in Table 7. In some embodiments, the amino acid sequence of the VL consists of an amino acid sequence at least 85%, 86%, 87%, 88%,Attorney Docket No.62801.72WO01 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 7. In some embodiments, the amino acid sequence of the VL consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 7. In some embodiments, the amino acid sequence of the VL consists of an amino acid sequence 100% identical to the amino acid sequence of a VL set forth in Table 7.

[0290] In some embodiments, the amino acid sequence of the VH comprises or consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 7; and the amino acid sequence of the VL comprises or consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 7.

[0291] In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 7; and the amino acid sequence of the VL comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 7. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 7; and the amino acid sequence of the VL comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 7. In some embodiments, the amino acid sequence of the VH comprises an amino acid sequence 100% identical to the amino acid sequence of a VH set forth in Table 7; and the amino acid sequence of the VL comprises an amino acid sequence 100% identical to the amino acid sequence of a VL set forth in Table 7.

[0292] In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 7; and the amino acid sequence of the VL consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acidAttorney Docket No.62801.72WO01 sequence of a VL set forth in Table 7. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VH set forth in Table 7; and the amino acid sequence of the VL consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a VL set forth in Table 7. In some embodiments, the amino acid sequence of the VH consists of an amino acid sequence 100% identical to the amino acid sequence of a VH set forth in Table 7; and the amino acid sequence of the VL consists of an amino acid sequence 100% identical to the amino acid sequence of a VL set forth in Table 7.

[0293] In some embodiments, the amino acid sequence of the HC comprises or consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a HC set forth in Table 7. In some embodiments, the amino acid sequence of the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a HC set forth in Table 7. In some embodiments, the amino acid sequence of the HC comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a HC set forth in Table 7. In some embodiments, the amino acid sequence of the HC comprises an amino acid sequence 100% identical to the amino acid sequence of a HC set forth in Table 7. In some embodiments, the amino acid sequence of the HC consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a HC set forth in Table 7. In some embodiments, the amino acid sequence of the HC consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a HC set forth in Table 7. In some embodiments, the amino acid sequence of the HC consists of an amino acid sequence 100% identical to the amino acid sequence of a HC set forth in Table 7.

[0294] In some embodiments, the amino acid sequence of the LC comprises or consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a LC set forth in Table 7. In some embodiments, the amino acid sequence of the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%Attorney Docket No.62801.72WO01 identical to the amino acid sequence of a LC set forth in Table 7. In some embodiments, the amino acid sequence of the LC comprises an amino acid sequence at 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a LC set forth in Table 7. In some embodiments, the amino acid sequence of the LC comprises an amino acid sequence 100% identical to the amino acid sequence of a LC set forth in Table 7. In some embodiments, the amino acid sequence of the LC consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a LC set forth in Table 7. In some embodiments, the amino acid sequence of the LC consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a LC set forth in Table 7. In some embodiments, the amino acid sequence of the LC consists of an amino acid sequence 100% identical to the amino acid sequence of a LC set forth in Table 7.

[0295] In some embodiments, the amino acid sequence of the HC comprises or consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a HC set forth in Table 7; and the amino acid sequence of the LC comprises or consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a LC set forth in Table 7.

[0296] In some embodiments, the amino acid sequence of the HC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a HC set forth in Table 7; and the amino acid sequence of the LC comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a LC set forth in Table 7. In some embodiments, the amino acid sequence of the HC comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a HC set forth in Table 7; and the amino acid sequence of the LC comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a LC set forth in Table 7. In some embodiments, the amino acid sequence of the HC comprises an amino acid sequence 100% identical to the amino acid sequence of a HC set forth in Table 7; and the amino acid sequence of the LC comprises an amino acid sequence 100% identical to the amino acidAttorney Docket No.62801.72WO01 sequence of a LC set forth in Table 7.

[0297] In some embodiments, the amino acid sequence of the HC consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a HC set forth in Table 7; and the amino acid sequence of the LC consists of an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a LC set forth in Table 7. In some embodiments, the amino acid sequence of the HC consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a HC set forth in Table 7; and the amino acid sequence of the LC consists of an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a LC set forth in Table 7. In some embodiments, the amino acid sequence of the HC consists of an amino acid sequence 100% identical to the amino acid sequence of a HC set forth in Table 7; and the amino acid sequence of the LC consists of an amino acid sequence 100% identical to the amino acid sequence of a LC set forth in Table 7.

[0298] In some embodiments, the integrin (e.g., α4β7 integrin) binding domain comprises a VH that comprises: a CDR-H1, a CDR-H2, and a CDR-H3; and VL that comprises CDR-L1, a CDR-L2, and a CDR-L3.

[0299] In some embodiments, the amino acid sequence of CDR-H1 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 583, or the amino acid sequence set forth in SEQ ID NO: 583 comprising or consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H2 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 584, or the amino acid sequence set forth in SEQ ID NO: 584 comprising or consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H3 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 585, or the amino acid sequence set forth in SEQ ID NO: 585 comprising or consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L1 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 586, or the amino acid sequence set forth in SEQ ID NO: 586 comprising or consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L2 comprises or consists of the amino acidAttorney Docket No.62801.72WO01 sequence set forth in SEQ ID NO: 587, or the amino acid sequence set forth in SEQ ID NO: 587 comprising or consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of CDR-L3 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 588, or the amino acid sequence set forth in SEQ ID NO: 588 comprising or consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.).

[0300] In some embodiments, the amino acid sequence of CDR-H1 comprises the amino acid sequence set forth in SEQ ID NO: 583, or the amino acid sequence set forth in SEQ ID NO: 583 comprising or consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H2 comprises the amino acid sequence set forth in SEQ ID NO: 584, or the amino acid sequence set forth in SEQ ID NO: 584 comprising or consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H3 comprises the amino acid sequence set forth in SEQ ID NO: 585, or the amino acid sequence set forth in SEQ ID NO: 585 comprising or consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L1 comprises the amino acid sequence set forth in SEQ ID NO: 586, or the amino acid sequence set forth in SEQ ID NO: 586 comprising or consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L2 comprises the amino acid sequence set forth in SEQ ID NO: 587, or the amino acid sequence set forth in SEQ ID NO: 587 comprising or consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of CDR-L3 comprises the amino acid sequence set forth in SEQ ID NO: 588, or the amino acid sequence set forth in SEQ ID NO: 588 comprising or consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.).

[0301] In some embodiments, the amino acid sequence of CDR-H1 comprises the amino acid sequence set forth in SEQ ID NO: 583, or the amino acid sequence set forth in SEQ ID NO: 583 comprising 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H2 comprises the amino acid sequence set forth in SEQ ID NO: 584, or the amino acid sequence set forth in SEQ ID NO: 584 comprising 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H3 comprises the amino acid sequence set forth in SEQ ID NO: 585, or the amino acid sequence setAttorney Docket No.62801.72WO01 forth in SEQ ID NO: 585 comprising 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L1 comprises the amino acid sequence set forth in SEQ ID NO: 586, or the amino acid sequence set forth in SEQ ID NO: 586 comprising 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L2 comprises the amino acid sequence set forth in SEQ ID NO: 587, or the amino acid sequence set forth in SEQ ID NO: 587 comprising 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); and the amino acid sequence of CDR-L3 comprises the amino acid sequence set forth in SEQ ID NO: 588, or the amino acid sequence set forth in SEQ ID NO: 588 comprising 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.).

[0302] In some embodiments, the amino acid sequence of CDR-H1 comprises the amino acid sequence set forth in SEQ ID NO: 583, or the amino acid sequence set forth in SEQ ID NO: 583 consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H2 comprises the amino acid sequence set forth in SEQ ID NO: 584, or the amino acid sequence set forth in SEQ ID NO: 584 consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-H3 comprises the amino acid sequence set forth in SEQ ID NO: 585, or the amino acid sequence set forth in SEQ ID NO: 585 consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L1 comprises the amino acid sequence set forth in SEQ ID NO: 586, or the amino acid sequence set forth in SEQ ID NO: 586 consisting of 1, 2, or 3 amino acid modifications (e.g., substitution, deletion, addition, etc.); the amino acid sequence of CDR-L2 comprises the amino acid sequence set forth in SEQ ID NO: 587, or the amino acid sequence set forth in SEQ ID NO: 58...

Claims

Attorney Docket No.62801.72WO01 CLAIMS What is claimed is:

1. A fusion protein comprising a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 388 or 387-389 or 390-454; and a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

2. A fusion protein comprising (a) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; and any one or more (e.g., 1, 2, 3, or 4) of (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454; (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464; (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576; and / or (a-1) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

3. The fusion protein of claim 2, wherein the fusion protein comprises (a) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; andAttorney Docket No.62801.72WO01 (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

4. The fusion protein of claim 2, wherein the fusion protein comprises (a) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; and (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

5. The fusion protein of claim 2, wherein the fusion protein comprises (a) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; and (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576.

6. The fusion protein of claim 2, wherein the fusion protein comprises (a) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; and (a-1) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

7. A fusion protein comprising (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454; and any one or more (e.g., 1, 2, 3, or 4) ofAttorney Docket No.62801.72WO01 (a) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464; (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576; and / or (b-1) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

8. The fusion protein of claim 7, wherein the fusion protein comprises (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454; and (a) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

9. The fusion protein of claim 7, wherein the fusion protein comprises (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454; and (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

10. The fusion protein of claim 7, wherein the fusion protein comprises (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 388; andAttorney Docket No.62801.72WO01 (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

455.

11. The fusion protein of claim 10, wherein the fusion protein comprises (b) a protein comprising an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 388; and (c) a protein comprising an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

455.

12. The fusion protein of claim 10, wherein the fusion protein comprises (b) a protein comprising an amino acid sequence at least about 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 388; and (c) a protein comprising an amino acid sequence at least about 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

455.

13. The fusion protein of claim 10, wherein the fusion protein comprises (b) a protein comprising the amino acid sequence set forth in SEQ ID NO: 388; and (c) a protein comprising the amino acid sequence set forth in SEQ ID NO:

455.

14. The fusion protein of claim 6, wherein the fusion protein comprises (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 419; and (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

455.

15. The fusion protein of claim 14, wherein the fusion protein comprises (b) a protein comprising an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 419; andAttorney Docket No.62801.72WO01 (c) a protein comprising an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

455.

16. The fusion protein of claim 14, wherein the fusion protein comprises (b) a protein comprising an amino acid sequence at least about 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 419; and (c) a protein comprising an amino acid sequence at least about 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

455.

17. The fusion protein of claim 14, wherein the fusion protein comprises (b) a protein comprising the amino acid sequence set forth in SEQ ID NO: 419; and (c) a protein comprising the amino acid sequence set forth in SEQ ID NO:

455.

18. The fusion protein of claim 7, wherein the fusion protein comprises (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454; and (b-1) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

19. A fusion protein comprising (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464; and any one or more (e.g., 1, 2, 3, or 4) of (a) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454;Attorney Docket No.62801.72WO01 (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576; and / or (c-1) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

20. The fusion protein of claim 19, wherein the fusion protein comprises (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464; and (a) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

21. The fusion protein of claim 19, wherein the fusion protein comprises (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464; and (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

22. The fusion protein of claim 18, wherein the fusion protein comprises (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464; and (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576.

23. The fusion protein of claim 19, wherein the fusion protein comprises (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464; andAttorney Docket No.62801.72WO01 (c-1) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

24. A fusion protein comprising (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576; and any one or more (e.g., 1, 2, 3, or 4) of (a) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454; (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464; and / or (d-1) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576.

25. The fusion protein of claim 24, wherein the fusion protein comprises (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576; and (a) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

26. The fusion protein of claim 24, wherein the fusion protein comprises (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576; andAttorney Docket No.62801.72WO01 (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

27. The fusion protein of claim 24, wherein the fusion protein comprises (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576; and (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

28. The fusion protein of claim 24, wherein the fusion protein comprises (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576; and (d-1) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576.

29. The fusion protein of any one of the preceding claims, wherein fusion protein comprises (a) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

30. The fusion protein of any one of the preceding claims, wherein fusion protein comprises(b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

31. The fusion protein of any one of the preceding claims, wherein fusion protein comprises(c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

32. The fusion protein of any one of the preceding claims, wherein fusion protein comprises(d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%,Attorney Docket No.62801.72WO01 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576.

33. The fusion protein of any one of the preceding claims, wherein protein (a) specifically binds the human IL-10 Receptor (hIL-10R) (e.g., hIL-10Rβ, hIL-10Rα), for example wherein protein (a) specifically binds hIL-10Rβ.

34. The fusion protein of any one of the preceding claims, wherein protein (a) is a hIL-10R agonist.

35. The fusion protein of any one of the preceding claims, wherein protein (a-1) specifically binds the hIL-10R (e.g., hIL-10Rβ, hIL-10Rα).

36. The fusion protein of any one of the preceding claims, wherein protein (a-1) specifically binds hIL-10Rβ.

37. The fusion protein of any one of the preceding claims, wherein protein (a-1) is a hIL-10R agonist.

38. The fusion protein of any one of the preceding claims, wherein protein (a) and protein (a- 1) are the same or different.

39. The fusion protein of any one of the preceding claims, wherein the amino acid sequence of protein (a) is 100% identical to the amino acid sequence of protein (a-1).

40. The fusion protein of any one of the preceding claims, wherein the amino acid sequence of protein (a) is not 100% identical to the amino acid sequence of protein (a-1).

41. The fusion protein of any one of the preceding claims, wherein protein (b) specifically binds human TL1A (hTL1A).

42. The fusion protein of any one of the preceding claims, wherein protein (b) inhibits or reduces (e.g., prevents) binding of hTL1A to human DR3 (hDR3).

43. The fusion protein of any one of the preceding claims, wherein protein (b) inhibits or reduces (e.g., prevents) activation of hDR3 signaling.

44. The fusion protein of any one of the preceding claims, wherein protein (b-1) specifically binds hTL1A.

45. The fusion protein of any one of the preceding claims, wherein protein (b-1) inhibits or reduces (e.g., prevents) binding of hTL1A to hDR3.

46. The fusion protein of any one of the preceding claims, wherein protein (b-1) inhibits or reduces (e.g., prevents) activation of hDR3 signaling.Attorney Docket No.62801.72WO01 47. The fusion protein of any one of the preceding claims, wherein protein (b) and protein (b- 1) are the same or different.

48. The fusion protein of any one of the preceding claims, wherein the amino acid sequence of protein (b) is 100% identical to the amino acid sequence of protein (b-1).

49. The fusion protein of any one of the preceding claims, wherein the amino acid sequence of protein (b) is not 100% identical to the amino acid sequence of protein (b-1).

50. The fusion protein of any one of the preceding claims, wherein protein (c) specifically binds TNFα (hTNFα).

51. The fusion protein of any one of the preceding claims, wherein protein (c) inhibits or reduces (e.g., prevents) binding of hTNFα to human TNFR1 (hTNFR1) and / or human TNFR2 (hTNFR2).

52. The fusion protein of any one of the preceding claims, wherein protein (c) inhibits or reduces (e.g., prevents) activation of hTNFR1 and / or hTNFR2 signaling.

53. The fusion protein of any one of the preceding claims, wherein protein (c-1) specifically binds hTNFα.

54. The fusion protein of any one of the preceding claims, wherein protein (c-1) inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR1 and / or hTNFR2.

55. The fusion protein of any one of the preceding claims, wherein protein (c-1) inhibits or reduces (e.g., prevents) activation of hTNFR1 and / or hTNFR2 signaling.

56. The fusion protein of any one of the preceding claims, wherein protein (b) and protein (b- 1) are the same or different.

57. The fusion protein of any one of the preceding claims, wherein the amino acid sequence of protein (c) is 100% identical to the amino acid sequence of protein (c-1).

58. The fusion protein of any one of the preceding claims, wherein the amino acid sequence of protein (c) is not 100% identical to the amino acid sequence of protein (c-1).

59. The fusion protein of any one of the preceding claims, wherein protein (d) specifically binds human CD30L (hCD30L).

60. The fusion protein of any one of the preceding claims, wherein protein (d) inhibits or reduces (e.g., prevents) binding of hCD30L to human CD30 (hCD30).

61. The fusion protein of any one of the preceding claims, wherein protein (d) inhibits or reduces (e.g., prevents) activation of hCD30 signaling.Attorney Docket No.62801.72WO01 62. The fusion protein of any one of the preceding claims, wherein protein (d-1) specifically binds hCD30L.

63. The fusion protein of any one of the preceding claims, wherein protein (d-1) inhibits or reduces (e.g., prevents) binding of hCD30L to hCD30.

64. The fusion protein of any one of the preceding claims, wherein protein (d-1) inhibits or reduces (e.g., prevents) activation of hCD30 signaling.

65. The fusion protein of any one of the preceding claims, wherein protein (d) and protein (d- 1) are the same or different.

66. The fusion protein of any one of the preceding claims, wherein the amino acid sequence of protein (d) is 100% identical to the amino acid sequence of protein (d-1).

67. The fusion protein of any one of the preceding claims, wherein the amino acid sequence of protein (d) is not 100% identical to the amino acid sequence of protein (d-1).

68. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of specifically binding hIL-10R.

69. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of specifically binding hTL1A.

70. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of specifically binding TNFα.

71. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of specifically binding CD30L.

72. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of specifically binding hIL-10R and hTL1A.

73. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of specifically binding hIL-10R and hCD30L.

74. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously specifically binding hTL1A and hIL-10R.

75. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously specifically binding hTL1A and hTNFα.

76. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously specifically binding hTL1A and hCD30L.Attorney Docket No.62801.72WO01 77. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously specifically binding hTNFα and hIL-10R.

78. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously specifically binding hTNFα and hTL1A.

79. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously specifically binding hTNFα and hCD30L.

80. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously specifically binding hCD30L and hIL-10R.

81. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously specifically binding hCD30L and hTL1A.

82. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously specifically binding hCD30L and hTNFα.

83. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously specifically binding hIL-10R, hTL1A, and TNFα.

84. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously specifically binding hIL-10R, hTL1A, and CD30L.

85. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously specifically binding hIL-10R, CD30L, and TNFα.

86. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously specifically binding hTL1A, TNFα, and CD30L.

87. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously specifically binding hIL-10R, hTL1A, TNFα, and CD30L.

88. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of inhibiting or reducing (e.g., preventing) binding of hTL1A to hDR3.

89. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of inhibiting or reducing (e.g., preventing) binding of hTNFα to hTNFR1 and / or hTNFR2.

90. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of inhibiting or reducing (e.g., preventing) binding of hCD30L to hCD30.Attorney Docket No.62801.72WO01 91. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing (e.g., preventing) binding of hTL1A to hDR3 and hTNFα to hTNFR1 and / or hTNFR2.

92. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing (e.g., preventing) binding of hTL1A to hDR3 and hCD30L to hCD30.

93. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing (e.g., preventing) binding of hTNFα to hTNFR1 and / or hTNFR2 and hTL1A to hDR3.

94. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing (e.g., preventing) binding of hTNFα to hTNFR1 and / or hTNFR2 and hLTα to hTNFR1 and / or hTNFR2.

95. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing (e.g., preventing) binding of hTNFα to hTNFR1 and / or hTNFR2 and hCD30L to hCD30.

96. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing (e.g., preventing) binding of hCD30L to hCD30 and hTL1A to hDR3.

97. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing (e.g., preventing) binding of hCD30L to hCD30 and hTNFα to hTNFR1 and / or hTNFR2.

98. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing (e.g., preventing) binding of hTL1A to hDR3, hTNFα to hTNFR1 and / or hTNFR2, and hCD30L to hCD30.

99. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL-10R).

100. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3).Attorney Docket No.62801.72WO01 101. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2).

102. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of inhibiting or reducing hCD30 signaling (e.g., hCD30 signaling mediated by binding of hCD30L to hCD30).

103. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL- 10R) and inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3).

104. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL- 10R) and inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2).

105. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL- 10R) and inhibiting or reducing hCD30 signaling (e.g., hCD30 signaling mediated by binding of hCD30L to hCD30).

106. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3) and inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL-10R).

107. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3) and inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2).Attorney Docket No.62801.72WO01 108. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3) and inhibiting or reducing hCD30 signaling (e.g., hCD30 signaling mediated by binding of hCD30L to hCD30).

109. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2) and inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL-10R).

110. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2) and inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3).

111. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2) and / or hTNFR2 and inhibiting or reducing hCD30 signaling (e.g., hCD30 signaling mediated by binding of hCD30L to hCD30).

112. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing hCD30 signaling (e.g., hCD30 signaling mediated by binding of hCD30L to hCD30) and inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL-10R).

113. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing hCD30 signaling (e.g., hCD30 signaling mediated by binding of hCD30L to hCD30) and inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3).

114. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing hCD30 signaling (e.g., hCD30 signaling mediated by binding of hCD30L to hCD30) and inhibiting or reducing hTNFR1 and / or hTNFR2Attorney Docket No.62801.72WO01 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2).

115. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL- 10R), inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3), and inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2).

116. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL- 10R), inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3), and inhibiting or reducing hCD30 signaling (e.g., hCD30 signaling mediated by binding of hCD30L to hCD30).

117. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL- 10R), inhibiting or reducing hCD30 signaling (e.g., hCD30 signaling mediated by binding of hCD30L to hCD30), and inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2).

118. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3 inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2), and inhibiting or reducing hCD30 signaling (e.g., hCD30 signaling mediated by binding of hCD30L to hCD30).

119. The fusion protein of any one of the preceding claims, wherein the fusion protein is capable of simultaneously inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL- 10R), inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3), inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1Attorney Docket No.62801.72WO01 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2), and inhibiting or reducing hCD30 signaling (e.g., hCD30 signaling mediated by binding of hCD30L to hCD30).

120. A fusion protein comprising (a) an integrin binding domain; and one or more of (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454; (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464; and / or (e) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 465-576.

121. The fusion protein of claim 120, wherein the fusion protein comprises (a) an integrin binding domain; and (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

122. The fusion protein of claim 120 or 121, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

123. The fusion protein of claim 122, wherein the fusion protein comprises (a) an integrin binding domain; andAttorney Docket No.62801.72WO01 (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

388.

124. The fusion protein of claim 123, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

388.

125. The fusion protein of claim 123 or 124, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

388.

126. The fusion protein of any one of claim 123-125, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising the amino acid sequence set forth in SEQ ID NO:

388.

127. The fusion protein of claim 122, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

419.

128. The fusion protein of claim 127, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

419.

129. The fusion protein of claim 127 or 128, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

419.

130. The fusion protein of any one of claims 127-129, wherein the fusion protein comprises (a) an integrin binding domain; andAttorney Docket No.62801.72WO01 (c) a protein comprising the amino acid sequence set forth in SEQ ID NO:

419.

131. The fusion protein of claims 120-130, wherein the fusion protein comprises (a) an integrin binding domain; and (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

132. The fusion protein of claim 131, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

455.

133. The fusion protein of claim 131 or 132, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

455.

134. The fusion protein of any one of claims 131-133, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

455.

135. The fusion protein of any one of claims 131-134, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising the amino acid sequence set forth in SEQ ID NO:

455.

136. The fusion protein of any one of the preceding claims, wherein the fusion protein comprises (a) an integrin binding domain; (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; andAttorney Docket No.62801.72WO01 (b-1) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386.

137. The fusion protein of any one of claims 120-136, wherein the fusion protein comprises (a) an integrin binding domain; (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454; and (c-1) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

138. The fusion protein of any one of claims 120-137, wherein the fusion protein comprises (a) an integrin binding domain; and (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464; and (d-1) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

139. The fusion protein of any one of claims 120-138, wherein the fusion protein comprises (a) an integrin binding domain; and (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454.

140. The fusion protein of any one of claims 120-139, wherein the fusion protein comprises (a) an integrin binding domain; andAttorney Docket No.62801.72WO01 (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

141. The fusion protein of any one of claims 120-140, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454; and (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

142. The fusion protein of claim 141, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 388; and (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

455.

143. The fusion protein of claim 142, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 388; and (d) a protein comprising an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

455.

144. The fusion protein of claim 142 or 143, wherein the fusion protein comprisesAttorney Docket No.62801.72WO01 (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 388; and (d) a protein comprising an amino acid sequence at least about 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

455.

145. The fusion protein of any one of claims 142-144, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising the amino acid sequence set forth in SEQ ID NO: 388; and (d) a protein comprising the amino acid sequence set forth in SEQ ID NO:

455.

146. The fusion protein of claim 141, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 419; and (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

455.

147. The fusion protein of claim 146, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 419; and (d) a protein comprising an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO:

455.

148. The fusion protein of claim 146 or 147, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising an amino acid sequence at least about 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 419; and (d) a protein comprising an amino acid sequence at least about 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 455.Attorney Docket No.62801.72WO01 149. The fusion protein of any one of claims 146-148, wherein the fusion protein comprises (a) an integrin binding domain; and (c) a protein comprising the amino acid sequence set forth in SEQ ID NO: 419; and (d) a protein comprising the amino acid sequence set forth in SEQ ID NO:

455.

150. The fusion protein of any one of claims 120-149, wherein the fusion protein comprises (a) an integrin binding domain; (b) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 34-386; (c) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 387-454; and (d) a protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 455-464.

151. The fusion protein of any one of claims 120-150, wherein the integrin binding domain comprises a full-length antibody, a single chain variable fragment (scFv), Fab, single domain antibody (sdAb), Fab-Fc, scFv-Fc, or sdAb-Fc.

152. The fusion protein of any one of claims 120-151, wherein the integrin binding domain specifically binds a plurality of integrins.

153. The fusion protein of any one of claims 120-152, wherein the integrin binding domain specifically binds one or more integrin expressed on surface of one or more immune cell (e.g., T cells).

154. The fusion protein of any one of claims 120-153, wherein the integrin binding domain specifically binds one or more of integrin α1β1, α2β1, α10β1, α11β1, α5β1, α8β1, α5β1, α5β3, α5β5, α5β6, α5β8, αIIbβ3, α3β1, α6β1, α7β1, α6β4, α4β1, α9β1, α4β7, αEβ7, αLβ2, αMβ2, αXβ2, and / or αDβ2.

155. The fusion protein of any one of claims 120-154, wherein the integrin binding domain specifically binds integrin α4β7.

156. The fusion protein of any one of claims 120-155, wherein the integrin binding domain comprises a variable heavy chain (VH) region that comprises three complementarity determiningAttorney Docket No.62801.72WO01 regions: VH CDR1, VH CDR2, and VH CDR3; and a variable light chain (VL) region that comprises three complementarity determining regions: VL CDR1, VL CDR2, and VL CDR3, wherein the amino acid sequence of VH CDR1 comprises the amino acid sequence SEQ ID NO: 583, or the amino acid sequence of SEQ ID NO: 583 comprising 1, 2, or 3 amino acid variations; the amino acid sequence of VH CDR2 comprises the amino acid sequence SEQ ID NO: 584, or the amino acid sequence of SEQ ID NO: 584 comprising 1, 2, or 3 amino acid variations; the amino acid sequence of VH CDR3 comprises the amino acid sequence SEQ ID NO: 585, or the amino acid sequence of SEQ ID NO: 585 comprising 1, 2, or 3 amino acid variations; and the amino acid sequence of VL CDR1 comprises the amino acid sequence SEQ ID NO: 586, or the amino acid sequence of SEQ ID NO: 586 comprising 1, 2, or 3 amino acid variations; the amino acid sequence of VL CDR2 comprises the amino acid sequence SEQ ID NO: 587, or the amino acid sequence of SEQ ID NO: 587 comprising 1, 2, or 3 amino acid variations; and the amino acid sequence of VL CDR3 comprises the amino acid sequence SEQ ID NO: 588, or the amino acid sequence of SEQ ID NO: 588 comprising 1, 2, or 3 amino acid variations.

157. The fusion protein of any one of claims 120-156, wherein the integrin binding domain comprises a VH region that comprises three complementarity determining regions: VH CDR1, VH CDR2, and VH CDR3; and a VL region that comprises three complementarity determining regions: VL CDR1, VL CDR2, and VL CDR3, wherein the amino acid sequence of VH CDR1 comprises the amino acid sequence SEQ ID NO: 583; the amino acid sequence of VH CDR2 comprises the amino acid sequence SEQ ID NO: 584; the amino acid sequence of VH CDR3 comprises the amino acid sequence SEQ ID NO: 585; and the amino acid sequence of VL CDR1 comprises the amino acid sequence SEQ ID NO: 586; the amino acid sequence of VL CDR2 comprises the amino acid sequence SEQ ID NO: 587; and the amino acid sequence of VL CDR3 comprises the amino acid sequence SEQ ID NO:

588.

158. The method of any one of claims 120-157, wherein the VH region comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 589; and the VL region comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,Attorney Docket No.62801.72WO01 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:

590.

159. The fusion protein of any one of claims 120-158, wherein the fusion protein is capable of inhibiting or reducing (e.g., preventing) binding of an integrin to its cognate partner.

160. The fusion protein of any one of claims 120-159, wherein the fusion protein is capable of inhibiting or reducing (e.g., preventing) binding of integrin α4β7 to mucosal vascular addressin cell adhesion molecule 1 (MADCAM-1).

161. The fusion protein of any one of claims 120-160, wherein the fusion protein is capable of inhibiting or reducing (e.g., preventing) signaling by a cognate partner of an integrin (e.g., signaling mediated by binding of the integrin to the cognate partner).

162. The fusion protein of any one of claims 120-161, wherein the fusion protein is capable of inhibiting or reducing (e.g., preventing) MADCAM-1 signaling (e.g., signaling mediated by the binding of MADCMA-1 to integrin α4β7).

163. The fusion protein of any one of claims 120-162, wherein protein (b) specifically binds the human IL-10 Receptor (hIL-10R) (e.g., hIL-10Rβ, hIL-10Rα).

164. The fusion protein of any one of claims 120-163, wherein protein (b) specifically binds hIL-10Rβ.

165. The fusion protein of any one of claims 120-164, wherein protein (b) is a hIL-10R agonist.

166. The fusion protein of any one of claims 120-165, wherein protein (b-1) specifically binds the hIL-10R (e.g., hIL-10Rβ, hIL-10Rα).

167. The fusion protein of any one of claims 120-166, wherein protein (b-1) specifically binds hIL-10Rβ.

168. The fusion protein of any one of claims 120-167, wherein protein (b-1) is a hIL-10R agonist.

169. The fusion protein of any one of claims 120-168, wherein protein (b) and protein (b-1) are the same or different.

170. The fusion protein of any one of claims 120-169, wherein the amino acid sequence of protein (b) is 100% identical to the amino acid sequence of protein (b-1).

171. The fusion protein of any one of claims 120-170, wherein the amino acid sequence of protein (b) is not 100% identical to the amino acid sequence of protein (b-1).Attorney Docket No.62801.72WO01 172. The fusion protein of any one of claims 120-171, wherein protein (c) specifically binds human TL1A (hTL1A).

173. The fusion protein of any one of claims 120-172, wherein protein (c) inhibits or reduces (e.g., prevents) binding of hTL1A to human DR3 (hDR3).

174. The fusion protein of any one of claims 120-173, wherein protein (c) inhibits or reduces (e.g., prevents) activation of hDR3 signaling.

175. The fusion protein of any one of claims 120-174, wherein protein (c-1) specifically binds hTL1A.

176. The fusion protein of any one of claims 120-175, wherein protein (c-1) inhibits or reduces (e.g., prevents) binding of hTL1A to hDR3.

177. The fusion protein of any one of claims 120-176, wherein protein (c-1) inhibits or reduces (e.g., prevents) activation of hDR3 signaling.

178. The fusion protein of any one of claims 120-177, wherein protein (c) and protein (c-1) are the same or different.

179. The fusion protein of any one of claims 120-178, wherein the amino acid sequence of protein (c) is 100% identical to the amino acid sequence of protein (c-1).

180. The fusion protein of any one of claims 120-179, wherein the amino acid sequence of protein (c) is not 100% identical to the amino acid sequence of protein (c-1).

181. The fusion protein of any one of claims 120-180, wherein protein (d) specifically binds TNFα (hTNFα).

182. The fusion protein of any one of claims 120-181, wherein protein (d) inhibits or reduces (e.g., prevents) binding of hTNFα to human TNFR1 (hTNFR1) and / or human TNFR2 (hTNFR2).

183. The fusion protein of any one of claims 120-182, wherein protein (d) inhibits or reduces (e.g., prevents) activation of hTNFR1 and / or hTNFR2 signaling.

184. The fusion protein of any one of claims 120-183, wherein protein (d-1) specifically binds hTNFα.

185. The fusion protein of any one of claims 120-184, wherein protein (d-1) inhibits or reduces (e.g., prevents) binding of hTNFα to hTNFR1 and / or hTNFR2.

186. The fusion protein of any one of claims 120-185, wherein protein (d-1) inhibits or reduces (e.g., prevents) activation of hTNFR1 and / or hTNFR2 signaling.Attorney Docket No.62801.72WO01 187. The fusion protein of any one of claims 120-186, wherein protein (b) and protein (b-1) are the same or different.

188. The fusion protein of any one of claims 120-187, wherein the amino acid sequence of protein (d) is 100% identical to the amino acid sequence of protein (d-1).

189. The fusion protein of any one of claims 120-188, wherein the amino acid sequence of protein (d) is not 100% identical to the amino acid sequence of protein (d-1).

190. The fusion protein of any one of claims 120-189, wherein the fusion protein is capable of specifically binding hIL-10R.

191. The fusion protein of any one of claims 120-190, wherein the fusion protein is capable of specifically binding hTL1A.

192. The fusion protein of any one of claims 120-191, wherein the fusion protein is capable of specifically binding TNFα.

193. The fusion protein of any one of claims 120-192, wherein the fusion protein is capable of specifically binding hIL-10R and hTL1A.

194. The fusion protein of any one of claims 120-193, wherein the fusion protein is capable of simultaneously specifically binding hTL1A and hIL-10R.

195. The fusion protein of any one of claims 120-194, wherein the fusion protein is capable of simultaneously specifically binding hTL1A and hTNFα.

196. The fusion protein of any one of claims 120-195, wherein the fusion protein is capable of simultaneously specifically binding hTNFα and hIL-10R.

197. The fusion protein of any one of claims 120-196, wherein the fusion protein is capable of simultaneously specifically binding hTNFα and hTL1A.

198. The fusion protein of any one of claims 120-197, wherein the fusion protein is capable of simultaneously specifically binding hIL-10R, hTL1A, and TNFα.

199. The fusion protein of any one of claims 120-198, wherein the fusion protein is capable of specifically binding one or more integrin (e.g., integrin α4β7) and hIL-10R.

200. The fusion protein of any one of claims 120-199, wherein the fusion protein is capable of specifically binding one or more integrin (e.g., integrin α4β7) and hTL1A.

201. The fusion protein of any one of claims 120-200, wherein the fusion protein is capable of specifically binding one or more integrin (e.g., integrin α4β7) and TNFα.Attorney Docket No.62801.72WO01 202. The fusion protein of any one of claims 120-201, wherein the fusion protein is capable of specifically binding one or more integrin (e.g., integrin α4β7), hIL-10R, and hTL1A.

203. The fusion protein of any one of claims 120-202, wherein the fusion protein is capable of simultaneously specifically binding one or more integrin (e.g., integrin α4β7), hTL1A, and hIL- 10R.

204. The fusion protein of any one of claims 120-203, wherein the fusion protein is capable of simultaneously specifically binding one or more integrin (e.g., integrin α4β7), hTL1A, and hTNFα.

205. The fusion protein of any one of claims 120-204, wherein the fusion protein is capable of simultaneously specifically binding one or more integrin (e.g., integrin α4β7), hTNFα, and hIL- 10R.

206. The fusion protein of any one of claims 120-205, wherein the fusion protein is capable of simultaneously specifically binding one or more integrin (e.g., integrin α4β7), hTNFα, and hTL1A.

207. The fusion protein of any one of claims 120-206, wherein the fusion protein is capable of simultaneously specifically binding one or more integrin (e.g., integrin α4β7), hIL-10R, hTL1A, and TNFα.

208. The fusion protein of any one of claims 120-207, wherein the fusion protein is capable of inhibiting or reducing (e.g., preventing) binding of hTL1A to hDR3.

209. The fusion protein of any one of claims 120-208, wherein the fusion protein is capable of inhibiting or reducing (e.g., preventing) binding of hTNFα to hTNFR1 and / or hTNFR2.

210. The fusion protein of any one of claims 120-209, wherein the fusion protein is capable of simultaneously inhibiting or reducing (e.g., preventing) binding of hTL1A to hDR3 and hTNFα to hTNFR1 and / or hTNFR2.

211. The fusion protein of any one of claims 120-210, wherein the fusion protein is capable of simultaneously inhibiting or reducing (e.g., preventing) binding of hTNFα to hTNFR1 and / or hTNFR2 and hTL1A to hDR3.

212. The fusion protein of any one of claims 120-211, wherein the fusion protein is capable of simultaneously inhibiting or reducing (e.g., preventing) binding of hTNFα to hTNFR1 and / or hTNFR2 and hLTα to hTNFR1 and / or hTNFR2.Attorney Docket No.62801.72WO01 213. The fusion protein of any one of claims 120-212, wherein the fusion protein is capable of inhibiting or reducing (e.g., preventing) binding of one or more integrin to its cognate partner (e.g., integrin α4β7 to MADCAM-1) and hTL1A to hDR3.

214. The fusion protein of any one of claims 120-213, wherein the fusion protein is capable of inhibiting or reducing (e.g., preventing) binding of one or more integrin to its cognate partner (e.g., integrin α4β7 to MADCAM-1) and hTNFα to hTNFR1 and / or hTNFR2.

215. The fusion protein of any one of claims 120-214, wherein the fusion protein is capable of simultaneously inhibiting or reducing (e.g., preventing) binding of one or more integrin to its cognate partner (e.g., integrin α4β7 to MADCAM-1), hTL1A to hDR3, and hTNFα to hTNFR1 and / or hTNFR2.

216. The fusion protein of any one of claims 120-215, wherein the fusion protein is capable of simultaneously inhibiting or reducing (e.g., preventing) binding of one or more integrin to its cognate partner (e.g., integrin α4β7 to MADCAM-1), hTNFα to hTNFR1, and / or hTNFR2 and hTL1A to hDR3.

217. The fusion protein of any one of claims 120-216, wherein the fusion protein is capable of simultaneously inhibiting or reducing (e.g., preventing) binding of one or more integrin to its cognate partner (e.g., integrin α4β7 to MADCAM-1), hTNFα to hTNFR1, and / or hTNFR2 and hLTα to hTNFR1 and / or hTNFR2.

218. The fusion protein of any one of claims 120-217, wherein the fusion protein is capable of inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL-10R).

219. The fusion protein of any one of claims 120-218, wherein the fusion protein is capable of inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3).

220. The fusion protein of any one of claims 120-219, wherein the fusion protein is capable of inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2).

221. The fusion protein of any one of claims 120-220, wherein the fusion protein is capable of simultaneously inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL-10R)Attorney Docket No.62801.72WO01 and inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3).

222. The fusion protein of any one of claims 120-221, wherein the fusion protein is capable of simultaneously inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL-10R) and inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2).

223. The fusion protein of any one of claims 120-222, wherein the fusion protein is capable of simultaneously inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3) and inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL-10R).

224. The fusion protein of any one of claims 120-223, wherein the fusion protein is capable of simultaneously inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3) and inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2).

225. The fusion protein of any one of claims 120-224, wherein the fusion protein is capable of simultaneously inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2) and inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL-10R).

226. The fusion protein of any one of claims 120-225, wherein the fusion protein is capable of simultaneously inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2) and inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3).

227. The fusion protein of any one of claims 120-226, wherein the fusion protein is capable of simultaneously inducing or enhancing hIL-10R (e.g., hIL-10Rβ, hIL-10Rα) signaling (e.g., signaling mediated by binding of an immunomodulatory protein described herein to hIL-10R), inhibiting or reducing of hDR3 signaling (e.g., hDR3 signaling mediated by binding of hTL1A to hDR3), and inhibiting or reducing hTNFR1 and / or hTNFR2 signaling (e.g., hTNFR1 and / or hTNFR2 signaling mediated by binding of hTNFα to hTNFR1 and / or hTNFR2).Attorney Docket No.62801.72WO01 228. The fusion protein of any one of the preceding claims, wherein one or more of the proteins are indirectly operably connected through one or more linker (e.g., one or more linker protein).

229. The fusion protein of any one of claims 228, wherein the linker comprises a peptide about 2-50 amino acids in length (e.g., a glycine linker, a glycine / serine linker, etc.).

230. The fusion protein of claim 228 or 229, wherein the linker comprises an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 701-711.

231. The fusion protein of claim 228, wherein the linker comprises one or more Ig constant region.

232. The fusion protein of claim 228 or 231, wherein the linker comprises or consists of an Ig Fc region.

233. The fusion protein of claim 232, wherein the Ig Fc region comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of any protein set forth in any one of Tables 8-13 or set forth in any one of SEQ ID NOS: 632-700.

234. The fusion protein of any one of the preceding claims, wherein the protein comprises a half-life extension protein.

235. The fusion protein of claim 234, wherein the half-life extension protein comprises one or more Ig constant region.

236. The fusion protein of claim 234 or 235, wherein the half-life extension protein comprises or consists of an Ig Fc region.

237. The fusion protein of claim 236, wherein the Ig Fc region comprises an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of any protein set forth in any one of Tables 8-13 or set forth in any one of SEQ ID NOS: 632-700.

238. The fusion protein of any one of the preceding claims, further comprising one or more heterologous moiety.Attorney Docket No.62801.72WO01 239. The fusion protein of claim 238, wherein the heterologous moiety comprises a small molecule, protein, peptide, nucleic acid molecule (e.g., DNA molecule, RNA molecule), carbohydrate, lipid, synthetic polymer, carrier, or vector.

240. The fusion protein of claim 238 or 239, wherein the heterologous moiety is detectable (e.g., fluorescent agent, radiation agent, imaging agent, etc.).

241. The fusion protein of any one of claims 238-240, wherein the heterologous moiety is a radionuclide.

242. The fusion protein of any one of the preceding claims, wherein the fusion protein comprises a multimerization domain.

243. The fusion protein of any one of the preceding claims, wherein the fusion protein comprises a dimerization domain.

244. The fusion protein of claim 243, wherein the dimerization domain comprises one or more Ig constant region.

245. The fusion protein of claim 243 or 244, wherein the dimerization domain comprises of consists of an Ig Fc region.

246. The fusion protein of any one of claims 243-245, wherein the dimerization domain comprises an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 632-700.

247. A dimeric fusion protein comprising (a) a first protein comprising the fusion protein of any one of claims 243-246; and (b) a second protein comprising the fusion protein of any one of claim 243-246, wherein the dimerization domain of the first protein and the dimerization domain of the second protein mediate dimerization of the first and second proteins.

248. A multimeric fusion protein comprising (a) a first protein comprising the fusion protein of claim 242; and (b) a second protein comprising the fusion protein of claim 242, wherein the multimerization domain of the first protein and the multimerization domain of the second protein mediate multimerization of the first and second proteins.

249. The multimeric fusion protein of claim 248, further comprising a third protein comprising the fusion protein of any one of the preceding claims.

250. The fusion protein of any one of the preceding claims, comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,Attorney Docket No.62801.72WO01 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 593-612.

251. A fusion protein comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 593-612.

252. The fusion protein of any one of the preceding claims, wherein the fusion protein is a dimeric fusion protein comprising two polypeptides, wherein the amino acid sequence of the first polypeptide comprises an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 593-612; and the amino acid sequence of the second polypeptide comprises an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 593-612.

253. The fusion protein of claim 252, wherein the amino acid sequence of the first polypeptide is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of the second polypeptide.

254. The fusion protein of claim 253, wherein the amino acid sequence of the first polypeptide is 100% identical to the amino acid sequence of the second polypeptide.

255. A multimeric fusion protein comprising (a) a first protein comprising the fusion protein of claim 242; and (b) a second protein comprising the fusion protein of claim 242, wherein the multimerization domain of the first protein and the multimerization domain of the second protein mediate multimerization of the first and second proteins.

256. The fusion protein of any one of the preceding claims, wherein the fusion protein comprises a fusion protein set forth in Table 16, wherein each polypeptide of the fusion protein comprises an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of each polypeptide of the fusion protein set forth in Table 16.

257. The fusion protein of any one of the preceding claims, comprising an amino acid sequence at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 613-616 or 621-622.Attorney Docket No.62801.72WO01 258. The fusion protein of any one of the preceding claims, comprising a first polypeptide (e.g., a first light chain) comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 592; a second polypeptide (e.g., a first heavy chain) comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 617-620 or 623-626; a third polypeptide (e.g., a second light chain) comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 592; and a fourth polypeptide (e.g., a second heavy chain) comprising an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in any one of SEQ ID NOS: 617-620 or 623-626.

259. A conjugate comprising the fusion protein of any one of the preceding claims operably connected to a heterologous moiety (e.g., described herein).

260. A radioligand comprising the fusion protein of any one of the preceding claims operably connected to a radionuclide.

261. A fusion protein comprising the fusion protein of any one of the preceding claims operably connected to a heterologous protein.

262. One or more nucleic acid molecule encoding the fusion protein (or one or more polypeptide thereof) of any one of the preceding claims, the conjugate of claim 259, the radioligand of claim 260, or the fusion protein of claim 261.

263. A vector (e.g., expression vector) comprising the nucleic acid molecule of claim 262.

264. A carrier comprising the fusion protein of any one of claims 1-258, the conjugate of claim 259, the radioligand of claim 260, the fusion protein of claim 261, the nucleic acid molecule of claim 262, the vector of claim 263, the cell of any one of claims 267-268, the combination regimen of claim 270, the combination composition of claim 271, or the pharmaceutical composition of claim 269.

265. A carrier conjugated to the fusion protein of any one of claims 1-258, the conjugate of claim 259, the radioligand of claim 260, or the fusion protein of claim 261.Attorney Docket No.62801.72WO01 266. The carrier of claim 264 or 265, wherein the carrier is a lipid nanoparticle, liposome, lipoplex, or nanoliposome.

267. A cell (e.g., host cell) comprising the fusion protein of any one of claims 1-258, the conjugate of claim 259, the radioligand of claim 260, the fusion protein of claim 261, the nucleic acid molecule of claim 262, the vector of claim 263, the carrier of any one of claims 264-266, the combination regimen of claim 270, the combination composition of claim 271, or the pharmaceutical composition of claim 269.

268. A cell (e.g., a therapeutic cell) expressing the fusion protein of any one of claims 1-258, the conjugate of claim 259, the radioligand of claim 259, or the fusion protein of claim 260, on the surface of the cell.

269. A pharmaceutical composition comprising the fusion protein of any one of claims 1-258, the conjugate of claim 259, the radioligand of claim 260, the fusion protein of claim 261, the nucleic acid molecule of claim 262, the vector of claim 263, the carrier of any one of claims 264- 266, the combination regimen of claim 270, the combination composition of claim 271, or the cell of any one of claims 267-268; and a pharmaceutically acceptable excipient.

270. A combination regimen comprising at least two proteins (or one or more nucleic acid molecule encoding the same), wherein each of the at least two proteins comprises an IL-10 binding protein described herein, a TL1A binding protein described herein, a TNFα binding protein described herein, a CD30L binding protein described herein, or a fusion protein described herein (e.g., a fusion protein of any one of claims 1-258).

271. A combination composition (e.g., pharmaceutical composition) comprising at least two proteins (or one or more nucleic acid molecule encoding the same), wherein each of the at least two proteins comprises an IL-10 binding protein described herein, a TL1A binding protein described herein, a TNFα binding protein described herein, a CD30L binding protein described herein, or a fusion protein described herein (e.g., a fusion protein of any one of claims 1-258).

272. A kit comprising the fusion protein of any one of claims 1-258, the conjugate of claim 259, the radioligand of claim 260, the fusion protein of claim 261, the nucleic acid molecule of claim 262, the vector of claim 263, the carrier of any one of claims 264-266, the combination regimen of claim 270, the combination composition of claim 271, the cell of any one of claims 267-268, or the pharmaceutical composition of claim 269; and optionally instructions for using any one or more of the foregoing.Attorney Docket No.62801.72WO01 273. A method of delivering a fusion protein, a conjugate, a radioligand, a fusion protein, a nucleic acid molecule, a vector, a carrier, a combination regimen, a combination composition, a cell, or a pharmaceutical composition to a subject, the method comprising administering to the subject the fusion protein of any one of claims 1-258, the conjugate of claim 259, the radioligand of claim 260, the fusion protein of claim 261, the nucleic acid molecule of claim 262, the vector of claim 263, the carrier of any one of claims 264-266, the combination regimen of claim 270, the combination composition of claim 271, the cell of any one of claims 267-268, or the pharmaceutical composition of claim 269 to the subject.

274. A method of inhibiting or reducing (e.g., preventing) binding of a plurality of respective receptor ligand interactions in a subject in need thereof, the method comprising administering to the subject the fusion protein of any one of claims 1-258, the conjugate of claim 259, the radioligand of claim 260, the fusion protein of claim 261, the nucleic acid molecule of claim 262, the vector of claim 263, the carrier of any one of claims 264-266, the combination regimen of claim 270, the combination composition of claim 271, the cell of any one of claims 267-268, or the pharmaceutical composition of claim 269, to thereby inhibit or reduce (e.g., prevent) binding of a plurality of respective receptor ligand interactions in the subject.

275. A method of inhibiting or reducing (e.g., preventing) signaling mediated by a plurality of respective receptor ligand interactions in a subject in need thereof, the method comprising administering to the subject the fusion protein of any one of claims 1-258, the conjugate of claim 259, the radioligand of claim 260, the fusion protein of claim 261, the nucleic acid molecule of claim 262, the vector of claim 263, the carrier of any one of claims 264-266, the combination regimen of claim 270, the combination composition of claim 271, the cell of any one of claims 267-268, or the pharmaceutical composition of claim 269, to thereby inhibit or reduce (e.g., prevent) signaling mediated by a plurality of respective receptor ligand interactions in in the subject.

276. A method of suppressing or reducing (e.g., preventing) a pro-inflammatory immune response in a subject in need thereof, the method comprising administering to the subject the fusion protein of any one of claims 1-258, the conjugate of claim 259, the radioligand of claim 260, the fusion protein of claim 261, the nucleic acid molecule of claim 262, the vector of claim 263, the carrier of any one of claims 264-266, the combination regimen of claim 270, the combination composition of claim 271, the cell of any one of claims 267-268, or theAttorney Docket No.62801.72WO01 pharmaceutical composition of claim 269, to thereby suppress or reduce (e.g., prevent) a pro- inflammatory immune response in the subject.

277. A method of preventing, treating, or ameliorating a disease in a subject in need thereof, the method comprising administering to the subject the fusion protein of any one of claims 1- 258, the conjugate of claim 259, the radioligand of claim 260, the fusion protein of claim 261, the nucleic acid molecule of claim 262, the vector of claim 263, the carrier of any one of claims 264-266, the combination regimen of claim 270, the combination composition of claim 271, the cell of any one of claims 267-268, or the pharmaceutical composition of claim 269, to thereby prevent, treat, or ameliorate the disease in the subject.

278. The method of claim 277, wherein the disease is a pro-inflammatory disease (e.g., an autoimmune disease).

279. The method of claim 278, wherein the disease is a pro-inflammatory disease or an autoimmune disease.

280. The method of any one of claims 277-279, wherein the disease is inflammatory bowel disease, Crohn’s disease, or ulcerative colitis.

281. The method of any one of claims 273-280, wherein the subject is human.

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