Multivalent trap-antibody fusions

Abstract

The present disclosure relates to multivalent antibody fusions, methods for their production, and methods for their use. Specifically, aspects of the disclosure relate to trap-based bispecific molecules and methods for producing trap-based bispecific molecules, which may be used to effectively treat diseases with multiple causative signaling pathways.

Description

[Technical Field]

[0001] Incorporation by reference of priority applications This application claims priority to U.S. Provisional Patent Application No. 63 / 487,606, filed February 28, 2023, which is incorporated herein by reference in its entirety.

[0002] Sequence Listing Reference This application is being filed with an electronic Sequence Listing, which is provided as a file named KDIAK191WOSEQLIST.XML, was created and last updated on February 9, 2024, and is 85,255 bytes in size. The information in this electronic Sequence Listing is incorporated herein by reference in its entirety.

[0003] Technical Field The present disclosure relates to multivalent antibody fusions, methods for making and using same. [Background technology]

[0004] A multivalent molecule can bind to more than one target or more than one section of a target molecule. Summary of the Invention

[0005] Some embodiments provided herein are illustrated by the following provided embodiments, and are provided as possible combinations or overlapping embodiments:

[0006] A multivalent trap-antibody fusion and / or a multivalent trap-Fab fusion comprising a trap and an antibody or fragment thereof, wherein the antibody or fragment thereof comprises a heavy chain variable region (VH) comprising three complementarity-determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3; the trap and the antibody are connected in tandem by a linker; the trap-antibody fusion comprises both an interleukin (IL)-binding site and an antigen-binding site; and the IL-binding site and the antigen-binding site are located at separate positions on the trap-antibody fusion. In some embodiments disclosed herein, the trap-antibody fusion and / or trap-Fab fusion is bispecific. In some embodiments, these bispecific molecules are composed of an IL-1 trap fused to an anti-IL-6 antibody or anti-HTRA1 antibody, an IL-6 trap fused to an anti-HTRA1 antibody, and an IL-33 trap fused to an anti-IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα inhibitor. In some embodiments, the TNFα inhibitor comprises a TNFα trap. In some embodiments, the TNFα inhibitor comprises a TNFα VHH. In some embodiments, the bispecific molecule comprises a TNFα trap fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα VHH fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a VEGF inhibitor. In some embodiments, the VEGF inhibitor comprises a VEGF trap.

[0007] A multivalent interleukin (IL) trap-antibody fusion comprising an IL trap and an antibody or fragment thereof, wherein the antibody or fragment thereof comprises a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3; the IL trap comprises an IL receptor and an IL accessory protein; and the IL trap comprises an IL receptor and an IL accessory protein. The trap and antibody are connected in series by a linker; the IL trap-antibody fusion contains both an IL-binding site and an antigen-binding site; and the IL-binding site and the antigen-binding site are located at separate positions on the trap-antibody fusion. In some embodiments disclosed herein, the trap-antibody fusion and / or trap-Fab fusion are bispecific. In some embodiments, these bispecific molecules are composed of an IL-1 trap fused to an anti-IL-6 antibody or an anti-HTRA1 antibody, an IL-6 trap fused to an anti-HTRA1 antibody, and an IL-33 trap fused to an anti-IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα inhibitor. In some embodiments, the TNFα inhibitor comprises a TNFα trap. In some embodiments, the TNFα inhibitor comprises a TNFα VHH. In some embodiments, the bispecific molecule comprises a TNFα trap fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα VHH fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a VEGF inhibitor. In some embodiments, the VEGF inhibitor comprises a VEGF trap.

[0008] A multivalent interleukin (IL) trap-antibody fusion comprising an IL trap and an antibody, wherein the IL trap comprises an IL receptor and an IL accessory protein; and the antibody comprises a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, VH CDR3, VH CDR4, VH CDR5, VH CDR6, VH CDR7, VH CDR8, VH CDR9, VH CDR10, VH CDR11, VH CDR12, VH CDR13, VH CDR14, VH CDR15, VH CDR16, VH CDR17, VH CDR18, VH CDR19 ... and a light chain variable region (VL) comprising a VH CDR1, a VL CDR2, and a VL CDR3; the interleukin trap and antibody are connected in tandem by a linker; the interleukin trap-antibody fusion comprises both an IL-binding site and an antigen-binding site; binding of the IL trap-antibody fusion inhibits IL signaling; and binding of the IL trap-antibody fusion to an antigen inhibits antigen activity. In some embodiments disclosed herein, the trap-antibody fusion and / or trap-Fab fusion is bispecific. In some embodiments, these bispecific molecules are composed of an IL-1 trap fused to an anti-IL-6 antibody or an anti-HTRA1 antibody, an IL-6 trap fused to an anti-HTRA1 antibody, and an IL-33 trap fused to an anti-IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα inhibitor. In some embodiments, the TNFα inhibitor comprises a TNFα trap. In some embodiments, the TNFα inhibitor comprises a TNFα VHH. In some embodiments, the bispecific molecule comprises a TNFα trap fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα VHH fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a VEGF inhibitor. In some embodiments, the VEGF inhibitor comprises a VEGF trap.

[0009] A multivalent interleukin (IL) trap-Fab fusion comprising an IL trap and an antigen-binding fragment (Fab fragment), wherein the IL trap comprises an IL receptor and an IL accessory protein; the IL trap and the Fab fragment are connected in tandem by a linker; the IL trap-antibody fusion comprises both an IL-binding site and an antigen-binding site; and the IL-binding site and the antigen-binding site are located at separate locations on the trap-antibody fusion. In some embodiments disclosed herein, the trap-antibody fusion and / or trap-Fab fusion are bispecific. In some embodiments, these bispecific molecules are composed of an IL-1 trap fused to an anti-IL-6 antibody or an anti-HTRA1 antibody, an IL-6 trap fused to an anti-HTRA1 antibody, and an IL-33 trap fused to an anti-IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα inhibitor. In some embodiments, the TNFα inhibitor comprises a TNFα trap. In some embodiments, the TNFα inhibitor comprises a TNFα VHH. In some embodiments, the bispecific molecule comprises a TNFα trap fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα VHH fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a VEGF inhibitor. In some embodiments, the bispecific molecule comprises a VEGF inhibitor. In this case, the VEGF inhibitor comprises a VEGF trap.

[0010] A multivalent interleukin (IL) trap-Fab fusion comprising an IL trap and an antigen-binding fragment (Fab fragment), wherein the IL trap and antibody are connected in tandem by a linker. In some embodiments disclosed herein, the trap-antibody fusion and / or trap-Fab fusion is bispecific. In some embodiments, these bispecific molecules are composed of an IL-1 trap fused to an anti-IL-6 antibody or an anti-HTRA1 antibody, an IL-6 trap fused to an anti-HTRA1 antibody, and an IL-33 trap fused to an anti-IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα inhibitor. In some embodiments, the TNFα inhibitor comprises a TNFα trap. In some embodiments, the TNFα inhibitor comprises a TNFα VHH. In some embodiments, the bispecific molecule comprises a TNFα trap fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα VHH fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a VEGF inhibitor. In some embodiments, the VEGF inhibitor comprises a VEGF trap.

[0011] A method for inhibiting interleukin signaling in a subject includes administering an interleukin trap-antibody fusion, wherein the fusion comprises an IL-trap antibody; the antibody comprises a heavy chain variable region (VH) comprising three complementarity-determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3; the IL-trap-antibody fusion comprises an IL-binding site and an antigen-binding site; binding of the IL-trap-antibody fusion to an IL inhibits IL signaling; and binding of the IL-trap-antibody fusion to an antigen inhibits antigen activity. In some embodiments disclosed herein, the trap-antibody fusion and / or trap-Fab fusion are bispecific. In some embodiments, these bispecific molecules are composed of an IL-1 trap fused to an anti-IL-6 antibody or anti-HTRA1 antibody, an IL-6 trap fused to an anti-HTRA1 antibody, and an IL-33 trap fused to an anti-IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα inhibitor. In some embodiments, the TNFα inhibitor comprises a TNFα trap. In some embodiments, the TNFα inhibitor comprises a TNFα VHH. In some embodiments, the bispecific molecule comprises a TNFα trap fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα VHH fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a VEGF inhibitor. In some embodiments, the VEGF inhibitor comprises a VEGF trap.

[0012] A multivalent interleukin (IL) trap-antibody fusion comprising an IL trap and an antibody or fragment thereof, wherein the antibody or fragment thereof comprises a heavy chain variable region (VH) comprising three complementarity-determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3; the IL trap comprises an IL receptor and an IL accessory protein; the IL trap and the antibody are connected in tandem by a linker; the IL trap-antibody fusion comprises both an IL-binding site and an antigen-binding site; the IL-binding site and the antigen-binding site are located at separate positions on the trap-antibody fusion; and the multivalent IL trap-antibody fusion is conjugated to a polymer. In some embodiments disclosed herein, the trap-antibody fusion and / or trap-Fab fusion are bispecific. In some embodiments, these bispecific molecules are composed of an IL-1 trap fused to an anti-IL-6 antibody or an anti-HTRA1 antibody, an IL-6 trap fused to an anti-HTRA1 antibody, and an IL-33 trap fused to an anti-IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα inhibitor. In some embodiments, the TNFα inhibitor comprises a TNFα trap. In some embodiments, the TNFα inhibitor comprises a TNFα trap. In some embodiments, the bispecific molecule comprises a TNFα VHH. In some embodiments, the bispecific molecule comprises a TNFα trap fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα VHH fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a VEGF inhibitor. In some embodiments, the VEGF inhibitor comprises a VEGF trap.

[0013] A multivalent interleukin (IL) trap-antibody fusion comprising an IL trap and an antibody, wherein the IL trap comprises an IL receptor and an IL accessory protein; and the antibody comprises a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, VH CDR3, VH CDR4, VH CDR5, VH CDR6, VH CDR7, VH CDR8, VH CDR9, VH CDR10, VH CDR11, VH CDR12, VH CDR13, VH CDR14, VH CDR15, VH CDR16, VH CDR17, VH CDR18, VH CDR19 ... and a light chain variable region (VL) comprising a VH CDR1, a VL CDR2, and a VL CDR3; the interleukin trap and the antibody are connected in tandem by a linker; the interleukin trap-antibody fusion comprises both an IL-binding site and an antigen-binding site; binding of the IL trap-antibody fusion inhibits IL signaling; binding of the IL trap-antibody fusion to an antigen inhibits antigen activity; and the multivalent IL trap-antibody fusion is conjugated to a polymer. In some embodiments disclosed herein, the trap-antibody fusion and / or trap-Fab fusion are bispecific. In some embodiments, these bispecific molecules are composed of an IL-1 trap fused to an anti-IL-6 antibody or an anti-HTRA1 antibody, an IL-6 trap fused to an anti-HTRA1 antibody, and an IL-33 trap fused to an anti-IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα inhibitor. In some embodiments, the TNFα inhibitor comprises a TNFα trap. In some embodiments, the TNFα inhibitor comprises a TNFα VHH. In some embodiments, the bispecific molecule comprises a TNFα trap fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα VHH fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a VEGF inhibitor. In some embodiments, the VEGF inhibitor comprises a VEGF trap.

[0014] A multivalent interleukin (IL) trap-Fab fusion comprising an IL trap and an antigen-binding fragment (Fab fragment), wherein the IL trap comprises an IL receptor and an IL accessory protein; the IL trap and the Fab fragment are connected in tandem by a linker; the IL trap-Fab fusion comprises both an IL-binding site and an antigen-binding site; the IL-binding site and the antigen-binding site are located at separate positions on the trap-Fab fusion; and the multivalent IL trap-antibody fusion is conjugated to a polymer. In some embodiments disclosed herein, the trap-antibody fusion and / or trap-Fab fusion are bispecific. In some embodiments, these bispecific molecules are composed of an IL-1 trap fused to an anti-IL-6 antibody or an anti-HTRA1 antibody, an IL-6 trap fused to an anti-HTRA1 antibody, and an IL-33 trap fused to an anti-IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα inhibitor. In some embodiments, the TNFα inhibitor comprises a TNFα trap. In some embodiments, the TNFα inhibitor comprises a TNFα VHH. In some embodiments, the bispecific molecule comprises a TNFα trap fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα VHH fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a VEGF inhibitor. In some embodiments, the VEGF inhibitor comprises a VEGF trap.

[0015] A multivalent interleukin (IL) trap-Fab fusion comprising an IL trap and an antigen-binding fragment (Fab fragment), wherein the IL trap and Fab are connected in series by a linker; and the multivalent IL trap-Fab fusion is conjugated to a polymer.

[0016] A method for treating a cytokine in a subject, comprising administering an interleukin trap-antibody fusion. For example, but not limited to, a method for inhibiting interleukin signaling, wherein the fusion comprises an IL trap antibody; the antibody comprises a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3; the IL trap-antibody fusion comprises an IL-binding site and an antigen-binding site; binding of the IL trap-antibody fusion to an IL inhibits IL signaling; binding of the IL trap-antibody fusion to an antigen inhibits antigen activity; and the multivalent IL trap-antibody fusion is conjugated to a polymer. In some embodiments disclosed herein, the trap-antibody fusion and / or trap-Fab fusion are bispecific. In some embodiments, these bispecific molecules are composed of an IL-1 trap fused to an anti-IL-6 antibody or an anti-HTRA1 antibody, an IL-6 trap fused to an anti-HTRA1 antibody, and an IL-33 trap fused to an anti-IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα inhibitor. In some embodiments, the TNFα inhibitor comprises a TNFα trap. In some embodiments, the TNFα inhibitor comprises a TNFα VHH. In some embodiments, the bispecific molecule comprises a TNFα trap fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a TNFα VHH fused to an IL-6 antibody. In some embodiments, the bispecific molecule comprises a VEGF inhibitor. In some embodiments, the VEGF inhibitor comprises a VEGF trap. [Brief explanation of the drawings]

[0017] [Figure 1] FIG. 1 is a representative illustration of several embodiments of multivalent interleukin (IL) trap-antibody fusions. [Figure 2] FIG. 2 is a representative illustration of several embodiments of a multivalent interleukin (IL) trap-antibody fusion binding to an IL and an antigen. [Figure 3]FIG. 3 is a flow chart and representative illustration of some embodiments of methods for inhibiting interleukin signaling. [Figure 4] Figure 4 is a schematic diagram showing several embodiments of IL-1 Trap and IgG fusion constructs. The dark crescent represents IL1R1 or IL1R2. The light crescent represents IL1RAcP. [Figure 5] Figure 5 shows an overlay of SPR sensorgrams demonstrating that IL-1 trap anti-HTRA1 (TA97) can simultaneously bind to both IL-1β and HTRA1. SPR is obtained by injecting HTRA1 followed by IL-1β (top sensorgram) or IL-1β followed by HTRA1 (bottom sensorgram). [Figure 6] Figure 6 shows a graph of the measured and predicted SPR responses when HTRA1 followed by IL-1β (left) or IL-1β followed by HTRA1 (right) was injected onto a surface immobilized with two different configurations of IL-1-trapped anti-HTRA1 (TA97 and TA98) and anti-HTRA1 antibody (aHTRA1.36). [Figure 7] Figure 7 shows that IL-1 trap anti-HTRA1 (TA97) efficiently inhibits HTRA1 activity, even when bound to IL-1β. HTRA1 activity measured in the H2-Opt assay is plotted against the logarithmic scale of trap-antibody concentration (M). Open squares indicate that HTRA1 activity was inhibited even in the presence of excess IL-1β. [Figure 8] FIG. 8 demonstrates that the mass of IL-1 trap anti-HTRA1(TA105) shifts accordingly upon binding to HTRA1 and / or IL-1β, as measured by mass photometry. [Figure 9] Figure 9 shows the pH-dependent (top panel) and NaCl concentration-dependent (bottom panel) thermal stability of IL-1 Trap x anti-HTRA1 (TA97). Each point represents the mean Tm obtained from triplicates measured by DSF. [Figure 10] FIG. 10 shows SDS-PAGE of IL-1 trap anti-HTRA1 (TA105) before and after biopolymer conjugation. [Figure 11] FIG. 11 demonstrates that biopolymer-conjugated IL-1 trap anti-HTRA1 (TA105) binds to IL-1β in an IL-1β Lumit assay. [Figure 12] FIG. 12 demonstrates that biopolymer-conjugated IL-1 trap anti-HTRA1 (TA105) inhibits the proteolytic activity of HTRA1 as measured by the H2-opt assay. [Figure 13] FIG. 13 shows SDS-PAGE of IL-1 trap anti-IL-6 Fab (TF2) before and after biopolymer conjugation. [Figure 14] FIG. 14 demonstrates that biopolymer-conjugated IL-1 trap anti-IL-6 Fab (TF2) competitively binds to IL-1β in an IL-1β sandwich ELISA. [Figure 15] Figure 15 demonstrates that biopolymer-conjugated IL-1 trap anti-IL-6 Fab (TF2) inhibits IL-6 binding to IL-6Rα in the IL-6 / IL-6Rα DuoSet ELISA. [Figure 16] FIG. 16 is an illustrative illustration of several polymer-conjugated multivalent interleukin (IL) trap-antibody fusions. [Figure 17-1] Figure 17-1 shows representative embodiments of the full length and individual regions of the IL-1 receptor sequence, the IL-6 receptor sequence, the IL-33 receptor sequence, and the VEGF receptor sequence. [Figure 17-2] Figure 17-2 shows representative embodiments of the full length and individual regions of the IL-1 receptor sequence, the IL-6 receptor sequence, the IL-33 receptor sequence, and the VEGF receptor sequence. [Figure 17-3]Figure 17-3 shows representative embodiments of the full length and individual regions of the IL-1 receptor sequence, the IL-6 receptor sequence, the IL-33 receptor sequence, and the VEGF receptor sequence. [Figure 17-4] Figure 17-4 shows representative embodiments of the full length and individual regions of the IL-1 receptor sequence, the IL-6 receptor sequence, the IL-33 receptor sequence, and the VEGF receptor sequence. [Figure 18-1] Figure 18-1 shows some representative embodiments of IgG constant and variable region sequences. [Figure 18-2] Figure 18-2 shows some representative embodiments of IgG constant and variable region sequences. [Figure 18-3] Figure 18-3 shows some representative embodiments of IgG constant and variable region sequences. [Figure 19] FIG. 19 shows some representative embodiments of linkers suitable for use in connecting an IL receptor protein with an antibody variable domain. [Figure 20] FIG. 20 shows some representative embodiments of signal peptide sequences suitable for use in the trap-antibody fusions disclosed herein. [Figure 21-1] FIG. 21-1 shows some representative embodiments of full-length heavy chain sequences suitable for use in the trap-antibody fusions disclosed herein. [Figure 21-2] Figure 21-2 shows some representative embodiments of full-length heavy chain sequences suitable for use in the trap-antibody fusions disclosed herein. [Figure 21-3] Figure 21-3 shows some representative embodiments of full-length heavy chain sequences suitable for use in the trap-antibody fusions disclosed herein. [Figure 21-4] Figure 21-4 shows several representative embodiments of full-length heavy chain sequences suitable for use in the trap-antibody fusions disclosed herein. [Figure 22-1]Figure 22-1 shows some representative embodiments of full-length light chain sequences suitable for use in the trap-antibody fusions disclosed herein. [Figure 22-2] Figure 22-2 shows some representative embodiments of full-length light chain sequences suitable for use in the trap-antibody fusions disclosed herein. [Figure 22-3] Figure 22-3 shows some representative embodiments of full-length light chain sequences suitable for use in the trap-antibody fusions disclosed herein. [Figure 23] FIG. 23 shows several representative embodiments of full-length heavy chain sequences suitable for use in the trap-Fab fusions disclosed herein. [Figure 24] FIG. 24 shows several representative embodiments of full-length light chain sequences suitable for use in the trap-Fab fusions disclosed herein. [Figure 25] FIG. 25 is a table listing embodiments of indications for which administration of trap-antibody or trap-Fab fusions may be suitable. [Figure 26] Figure 26 shows OG1786. [Figure 27] Figure 27 shows OG1801. [Figure 28] Figure 28 shows OG1802. [Figure 29] Figure 29 demonstrates that IL-1 trap anti-IL-6 knobs-in-hole antibodies competitively bind to IL-1β in an IL-1β sandwich ELISA. [Figure 30] Figure 30 is a graph showing several embodiments of the IL-6 / IL-6Rα DuoSet ELISA demonstrating that IL-1 trap anti-IL-6 knobs-in-holes antibodies inhibit IL-6 binding to IL-6Rα, even in the presence of excess IL-1β. [Figure 31A]Figure 31A is a graph showing several embodiments of the measured and predicted SPR responses when IL-6 and then IL-1β are injected onto a surface immobilized with an IL-1-trapped anti-IL-6 knobs-in-hole antibody. [Figure 31B] Figure 31B is a graph showing several embodiments of the measured and predicted SPR responses when IL-1β and then IL-6 are injected onto a surface immobilized with an IL-1-trapped anti-IL-6 knobs-in-hole antibody. [Figure 32A] FIG. 32A graphs the measured and predicted SPR responses when IL-6 and then TNFα were injected onto a surface immobilized with a TNFα-trapped anti-IL-6 antibody. [Figure 32B] FIG. 32B graphs the measured and predicted SPR responses when TNFα and then IL-6 were injected onto a surface immobilized with a TNFα-trapped anti-IL-6 antibody. [Figure 33] FIG. 33 is a graph showing several embodiments demonstrating that the mass of an anti-TNFα VHH anti-IL-6 antibody (TA189) shifts accordingly upon binding to TNFα and / or IL-6, as measured by mass spectrometry. [Figure 34A] FIG. 34A is a graph showing several embodiments of the measured / predicted SPR response upon injection of IL-6 and then TNFα onto a surface immobilized with anti-TNFα VHH anti-IL-6 antibodies. [Figure 34B] FIG. 34B is a graph showing several embodiments of the measured / predicted SPR response upon injection of TNFα and then IL-6 onto a surface immobilized with anti-TNFα VHH anti-IL-6 antibodies. DETAILED DESCRIPTION OF THE INVENTION

[0018] Provided herein are multivalent antibody fusions, methods for their production, and methods for their use. Some aspects of the present disclosure relate to trap-based bispecific molecules and methods for producing trap-based bispecific molecules. In some embodiments, one or more of the multivalent antibody fusions and / or trap-based bispecific molecules can be used to effectively treat diseases with multiple causative signaling pathways. In some embodiments, the disease is eye inflammation or ocular inflammation.

[0019] Growth factors (GFs) and cytokines act in an intracrine, autocrine, or VEGF mediates important intercellular communication in a paracrine and paracrine manner. GFs and cytokines regulate cellular activities, including proliferation, differentiation, and migration, which ultimately result in various biological responses, such as tissue development, tissue homeostasis, and immune function; Kany S, Vollrath JT, Relja B. 2019. “Cytokines in Inflammatory Disease.” Int. J. Mol. Sci. 20: 6008-; Apte RS, Chen DS, Ferrara N. 2019. “VEGF in Signaling and Disease: Beyond Discovery and Development.”Cell 176: 1248-1264; Ren X, Zhao M, Lash B, Martino MM, Julier Z. 2020. “Growth Factor Engineering Strategies for Regenerative Medicine Applications.” Front. Bioeng. Biotechnol. 7. A common signaling mechanism utilized by GFs and cytokines involves the homo- or heteromultimerization of cognate receptors on the surface of responding cells upon ligand binding, triggering activation and downstream intracellular signaling; Atanasova M, Whitty A. 2012. “Understanding cytokine and growth factor receptor activation mechanisms.” Crit. Rev. Biochem. Mol. Biol. 47: 502-530. Receptors are transmembrane proteins; the extracellular domain (ECD) region recognizes and binds the ligand, while the intracellular portion exhibits intrinsic kinase activity or contains an “adapter” domain that interacts with kinases; Grotzinger J. 2002. “Molecular mechanisms of cytokine receptor activation.” Biochim. Biophys. Acta. Mol. Cell. Res. 1592: 215-223; Wang X, Lupardus P, LaPorte SL, Garcia KC. 2009. Structural Biology of Shared Cytokine Receptors. Annu. Rev. Anal. Chem. (Palo. Alto. Calif). 27: 29-60.

[0020] Cytokine dysregulation is associated with a myriad of health problems, including inflammatory diseases, age-related diseases, and cancer; Turner MD, Nedjai B, Hurst T, Pennington DJ. 2014. “Cytokines and chemokines: At the crossroads of cell signaling and inflammatory disease.” Biochim. Biophys. Acta. Mol. Cell. Res. 1843: 2563-2582; Rea IM, Gibson DS, McGILligan V, McNerlan SE, Alexander HD, Ross OA. 2018. “Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines.” Front. Immunol. 9; Morris RM, Mortimer TO, O'Neill KL. 2022. "Cytokines: Can Cancer Get the Message?" Cancers 14: 2178-. Cytokine-targeted therapy has shown clinical benefits. The molecular design of various drugs is based on the Fc-fusion format, in which an intact ECD domain is fused to the fragment crystallizable (Fc) region of immunoglobulin G (IgG); Economides AN, Carpenter LR, Rudge JS, Wong V, Koehler-Stec EM, Hartnett C, Pyles EA, Xu X, Daly TJ, Young MR, et al. 2002. “Cytokine traps: multi-component, high-af finity blockers of cytokine action.” Nat. Med. 9: 47-52; Scott LJ. 2014. “Etanercept: A Review of Its Use in Autoimmune Inflammatory Diseases.” Drugs 74: 1379-1410; Sophie R, Akhtar A, Sepah YJ, Ibrahim M, Bittencourt M, Do DV, Nguyen QD. 2012. “Aflibercept: a Potent Vascular Endothelial Growth Factor Antagonist for Neovascular Age-Related Macular Degeneration and Other Retinal Vascular Diseases.” Biol. Ther. 2. The Fc portion forms dimers through interdomain interactions and is further stabilized by interchain disulfide bridges. This, in turn, positions the receptors in close proximity, allowing the ECD domains to dimerize and bind to their targets with high affinity (trapping mechanism).

[0021] Bispecific antibodies have been shown to be a promising strategy for overcoming some of the fundamental limitations of monospecific antibody therapy, which cannot address the multiple inter-talking signaling pathways underlying target diseases. Although efforts have been made to address the immunogenicity, chain mismatching, and manufacturing scalability issues associated with multivalent molecules, there remains a need for the development of bispecific formats that effectively address these issues; Brinkmann U, Kontermann RE. 2017. "The making of bispecific antibodies." mAbs 9: 182-212; Godar et Godar M, de Haard H, Blanchetot C, Rasser J. 2018. "Therapeutic bispecific antibody formats: a patent applications review" (1994-2017). Expert. Opin. Ther. Pat. 28: 251-276. Thus, some aspects of the present disclosure relate to multivalent antibody fusions, methods for their production, and methods for their use.

[0022] Some embodiments of the present disclosure relate to trap-based bispecific molecules that utilize the natural dimer interface between the heavy chain variable (VH) and light chain variable (VL) regions present in antibodies. In this format, the receptor domain is linked in tandem to the VH and VL regions. This configuration positions the ECD in a favorable orientation for ligand binding. The heterodimeric nature of the VH:VL pairing allows for the design of homodimer- or heterodimer-based traps without further engineering (e.g., Fc knob-in-hole), while the complementarity-determining regions (CDRs) enable binding of a second target of interest.

[0023] Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. AMD is a complex disease with multiple etiological factors and no effective treatment is available; Fleckenstein M, Keenan TDL, Guymer RH, Chakravarthy U, Schmitz-Walckenberg S, Klaver CC, Wong WT, Chew EY. 2021; “Age-related macular degeneration.” Nat. Rev. Dis. Primers. 7. Research suggests that GFs and cytokines are involved in the development and progression of AMD. Inhibition of VEGF-A has been proven to effectively treat neovascularization and delay disease progression (Song D, Liu P, Shang K, Ma Y. 2022. “Application and mechanism of anti-VEGF drugs in age-related macular degeneration.” Front. Bioeng. Biotec hnol. 10), but do not address the underlying immune factors that may be associated with anti-VEGF treatment resistance. Currently, there are no effective treatments for the primary form of AMD (dry AMD), also known as geographic atrophy, which accounts for approximately 90% of cases. Genetic risk factors and a dysregulated inflammatory response create a complex interplay of signaling pathways, which likely hinders the development of effective monospecific therapies.

[0024] Overall, cytokines have been shown to play a pivotal role in the development of retinal diseases. Patients with AMD have been reported to have elevated serum levels of the proinflammatory cytokine interleukin-6 (IL-6). IL-6 has been observed to stimulate defective angiogenesis, which may be an indirect result of IL-6-mediated upregulation of VEGF expression. Furthermore, more direct functions of IL-6, such as endothelial cell proliferation and migration, have been reported in the presence of VEGF inhibitors, indicating that IL-6 angiogenic signaling occurs independently of VEGF. Other studies have shown that retinal pigment epithelial (RPE) cells release IL-1α upon death or under stress conditions, which may contribute to the recruitment of immune cells. Therefore, IL-1β production by activated microglial and macrophage cells may promote further macrophage recruitment to affected tissues, leading to photoreceptor and RPE cell death. Wooff Y, Man SM, Aggio-Bruce R, Natoli R, Fernando N. 2019. “IL-1 Family Members Mediate Cell Death, Inflammation and Angiogenesis in Retinal Degenerative Diseases.” Front. Immunol. 10.

[0025] Genome-wide association studies (GWAS) have identified a locus on human chromosome 10q26 associated with AMD risk, where two genes, ARMS2 and HTRA1, are located in close proximity to each other. These studies suggest a correlation between disease progression and a single nucleotide polymorphism (SNP) in the promoter region of HTRA1, resulting in increased HTRA1 expression. DeWan A, Liu M, Hartman S, Zhang SS-M, Liu DTL, Zhao C, Tam POS, Chan WM, Lam DSC, Snyder M, et al. 2006. “HTRA1 Promoter Polymorphism in Wet Age-Related Macular Degeneration.” Science 314: 989-992; Yang Z, Camp NJ, Sun H, Tong Z, Gibbs D, Cameron DJ, Chen H, Zhao Y, Pearson E, Li Gorski M, et al. 2015. “A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.” Nat. Genet. 48: 134-143. High-temperature requirement A1 (HTRA1) is a serine protease known to cleave multiple extracellular matrix (ECM) proteins and TGF-β family members; Lu ZG, May A, Dinh B, Lin V, Su F, Tran C, Adivikolanu H, Ehlen R, Che B, Wang ZH, et al. 2021. “The interplay of oxidati ive stress and ARMS2-HTRA1 genetic risk in neovascular AMD.” Vessel. Plus. 2021. It is hypothesized that cleavage of specific ECM proteins contributes to the accumulation of extracellular debris, which in turn sensitizes cells to inflammatory stimuli; Beguier F, Housset M, Roubeix C, Augustin S, Zagar Y, Nous C, Mathis T, Eandi C, Benchaboune M, Drame-Maigne A, et al. 2020. “The 10q26 Risk Haplotype of Age-Related Macular Degeneration Aggravates Subretinal Inflammation by Impairing Monocyte Elimination.” Immunity 53: 429-441.e8; Lin MK, Yang J, Hsu CW, Gore A, Bassuk AG, Brown LM, Colligan R, SengILlo JD, Mahajan VB, Tsang SH. 2018. "HTRA1, an age-related macular degeneration protease, processes extracellular matrix proteins EFEMP1 and TSP1. Aging. Cell. 17: e12710-". HTRA1 has also been shown to induce expression of inflammatory cytokines and VEGF, and overexpression of HTRA1 in the retina of a mouse model recapitulates key physiological markers of AMD. These data support the finding that HTRA1 risk alleles show strong and similar associations with wet and dry AMD.

[0026] In some embodiments, the present disclosure is directed to reducing the concurrent inflammation and defective angiogenesis that drive the pathogenesis of AMD.

[0027] In some embodiments, the present disclosure is directed to reducing inflammation of the eye or ocular inflammation.

[0028] Some embodiments of the present disclosure are directed to bispecific molecules that simultaneously block a combination of cytokines, GFs, and HTRA1 to reduce the concurrent inflammation and defective angiogenesis that drive the pathogenesis of AMD.

[0029] In some embodiments, these bispecific molecules are composed of an IL-1 trap fused to an anti-IL-6 antibody or an anti-HTRA1 antibody, an IL-6 trap fused to an anti-HTRA1 antibody, and an IL-33 trap fused to an anti-IL-6 antibody. Bispecific molecules were constructed using a heterodimeric trap fusion design to the VH and VL domains. Additionally, tandem Fab versions of anti-IL-6 were also created with an IL-1 trap (heterodimer) and a VEGF trap (homodimer). Each of these dual inhibitor molecules has the option of containing an unpaired cysteine ​​at its C-terminal region, which can be conjugated to a phosphorylcholine-based biopolymer for half-life extension. In some embodiments, the bispecific molecule comprises a TNFα inhibitor. In some embodiments, the TNFα inhibitor comprises a TNFα trap. In some embodiments, the TNFα inhibitor comprises a TNFα VHH.

[0030] definition As used herein, the term "interleukin" (IL) refers to one or more of a group of related proteins made by leukocytes (white blood cells) and other cells in the body. Interleukins are a type of cytokine that regulates immune responses.

[0031] As used herein, the term "cytokine" refers to a small protein, polypeptide, or peptide involved in inflammatory signaling, or a protein produced by one cell population that acts on another cell as an intercellular mediator or that has an autocrine effect on the cell that produces it.Cytokines include chemokines, interferons, interleukins, lymphokines, monokines, tumor necrosis factors, CCL1, CCl2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28, CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CXCL15, CXCL16, CXCL17, CX3CL1 , XCL1, XCL2, INFα, INFβ, INFγ, IL-1, IL-1α, IL-1β, IL-1Ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, I L-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-17A-F, IL-18, IL-19, IL- 20, IL-21, IL-22, IL-23, IL-24, IL-25, IL-26, IL-27, IL-28, IL-29, IL-30, IL-31, IL-32, IL-33, IL-34, IL-35, IL-36Ra, IL-36α, IL-36β, IL-36γ, IL-37, IL-38, GM-CSF, TNFα, TNFβ, TNFγ, TGF-I-3 Examples of such proteins include, but are not limited to, TNFSF4, TNFSF5, TNFSF6, TNFSF7, TNFSF8, TNFSF9, TNFSF10, TNFSF11, TNFSF12, TNFSF13, TNFSF13B, TNFSF14, TNFSF15, TNFSF18, or TNFSF19, leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), CNTF-like cytokine (CLC), cardiotrophin (CT), Kit ligand (KL), or any combination thereof.

[0032] As used herein, the terms "valence," "valency," or "valent" refer to the relative ability of a substance (e.g., an antibody) to act on, react with, or bind to a biological substrate (e.g., an antigen); the number of antigen binding sites an antibody has, or the number of antigenic determinants an antigen has. In some embodiments, valency refers to the number of binding sites on a molecule. In some embodiments, valency refers to the property of an atom or radical that describes the binding strength of the atom or radical, particularly in terms of the number of hydrogen atoms. In some embodiments, the substance or molecule is zerovalent, nonvalent, monovalent, univalent, divalent, bivalent, trivalent, tervalent, tetravalent, quadrivalent, pentavalent, quinquevalent, quinquivalent, hexavalent, sexivalent, heptavalent, septivalent, octavalent, nonavalent, decavalent, dodecavalent, polyvalent, or multivalent.

[0033] The term "antibody" includes intact antibodies and binding fragments thereof. A binding fragment refers to a molecule distinct from an intact antibody, which contains a portion of an intact antibody that binds to the antigen to which the intact antibody binds. Examples of binding fragments include Fv, Fab, Fab-SH, F(ab')2; diabodies; linear antibodies; single-chain antibody molecules (e.g., , scFv); and multispecific antibodies formed from antibody fragments. scFv antibodies are described in Houston JS. 1991. Methods in Enzymol. 203:46-96. Furthermore, antibody fragments include single-chain polypeptides having characteristics of a VH domain or region, i.e., which assembles with a VL domain or region to form a functional antigen-binding site, thereby providing the antigen-binding characteristics of a full-length antibody, or characteristics of a VL domain or region, i.e., which assembles with a VH domain or region to form a functional antigen-binding site, thereby providing the antigen-binding characteristics of a full-length antibody. The terms "domain" and "region" are used interchangeably.

[0034] As used herein, the term "antigen-binding fragment (Fab fragment)" refers to an antibody fragment that binds to an antigen. A Fab fragment contains one constant domain and one variable domain from each of the heavy and light chains.

[0035] The term "VHH domain," also known as VHH, VHH domain, VHH antibody fragment, and VHH antibody, was originally described as the antigen-binding immunoglobulin (Ig) (variable) domain of a "heavy chain antibody" (i.e., an antibody lacking light chains; Hamers-Casterman et al. (1993) Nature 363: 446-448). The term "VHH domain" was chosen to distinguish these variable domains from the heavy chain variable domains (referred to herein as "VH domains") and light chain variable domains (referred to herein as "VL domains") present in conventional four-chain antibodies. For further description of VHHs and nanobodies, see the review article by Muyldermans (Reviews in Molecular Biotechnology 74: 277-302, 2001).

[0036] An antibody specifically binds to its target antigen by at least 10 6 M -1, at least 10 7 M -1 , at least 10 8 M -1 , at least 10 9 M -1 , or at least 10 10 M -1 Specific binding means that the antibody or fusion protein has an affinity of at least 100%. Specific binding is detectably high and distinguishable in magnitude from nonspecific binding that occurs to at least one unrelated target. Specific binding can be the result of bond formation between specific functional groups or a specific spatial fit (e.g., lock-and-key type), whereas nonspecific binding is usually the result of van der Waals forces. However, specific binding does not necessarily mean that the antibody or fusion protein binds only to one target.

[0037] The basic antibody structural unit is a tetramer of subunits. Each tetramer contains two identical pairs of polypeptide chains, each pair consisting of one "light" chain (approximately 25 kDa) and one "heavy" chain (approximately 50-70 kDa). The amino-terminal portion of each chain contains a variable region or variable domain of approximately 100-110 or more amino acids, primarily responsible for antigen recognition. The terms "domain" and "region" are used interchangeably. This variable region is initially expressed linked to a cleavable signal peptide. A variable region without a signal peptide is sometimes referred to as a mature variable region. Thus, for example, a light chain mature variable region refers to a light chain variable region without the light chain signal peptide. However, the term "variable region" does not necessarily imply the presence of a signal sequence; in fact, the signal sequence is cleaved upon expression and secretion of the antibody or fusion protein. The pair of heavy and light chain variable regions defines the binding region of the antibody. The carboxy-terminal portions of the light and heavy chains define the light-chain constant region and the heavy-chain constant region, respectively. The heavy-chain constant region is primarily responsible for effector functions. In IgG antibodies, the heavy-chain constant region is divided into CH1, hinge, CH2, and CH3 regions. The CH1 region is linked to the light-chain constant region by disulfide bonds and non-covalent bonds. The hinge region is responsible for the binding of the antibody. The CH2 and CH3 regions provide flexibility between the binding and effector domains and also provide sites for intermolecular disulfide bonding between the two heavy chain constant domains within the tetrameric subunit. The CH2 and CH3 regions are the primary sites of effector function and binding to FcRs (i.e., FcRn and FcRγ).

[0038] Light chains are classified as either kappa or lambda. Heavy chains are classified as gamma, mu, alpha, delta, or epsilon, and define the antibody's isotype as IgG, IgM, IgA, IgD, and IgE, respectively. Within light and heavy chains, the variable and constant regions are joined by a "J" segment of about 12 or more amino acids, with the heavy chain also containing a "D" segment of about 10 or more amino acids. (For a review, see Fundamental Immunology (Paul, W., ed., 2nd ed. Raven Press, NY, 1989), Ch. 7) (incorporated by reference in its entirety for all purposes).

[0039] The mature variable regions of each light / heavy chain pair form the antibody binding site. Thus, an intact antibody has two binding sites, i.e., is bivalent. In natural antibodies, the binding sites are identical. However, bispecific antibodies, in which the two binding sites are different, can also be produced (e.g., Songsiv I Lai S, Lachmann PC. 1990). Bispecific antibody: a tool for diagnosis and treatment of disease. Clin Exp Immunol. 79:315-321; Kostelny SA, Cole MS, Tso JY. 1992. Formation of bispecific antibody by the use of leucine zippers. J Immunol. 148: 1547-1553). All variable regions exhibit the same overall structure, with relatively conserved framework regions (FR) connected by three hypervariable regions (also called complementarity-determining regions or CDRs). The CDRs from the two chains of each pair are aligned by the framework regions, enabling binding to a specific epitope. From the N-terminus to the C-terminus, both light and heavy chains comprise the FR1 domain, CDR1 domain, FR2 domain, CDR2 domain, FR3 domain, CDR3 domain, and FR4 domain. For convenience, the variable heavy chain CDRs are referred to as CDRs. H 1. CDR H 2, and CDR H 3, and the variable light chain CDRs are CDRs L 1. CDR L 2, and CDR LThe amino acid sequence of each domain is sometimes referred to as "domain 3." The amino acid assignment for each domain follows the definitions in Kabat EA, et al. 1987 and 1991. Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, MD) or Chothia C, Lesk AM. 1987. Canonical Structures for the Hypervariable Regions of Immunoglobulins. J Mol Biol 196:901-917; Chothia C, et al. 1989. Conformations of Immunoglobulin Hypervariable Regions. Nature 342:877-883. Kabat also provides a widely used numbering scheme (Kabat numbering) in which corresponding residues between different heavy chain variable regions or different light chain variable regions are assigned the same number. While Kabat numbering can be used for antibody constant regions, EU numbering is more commonly used, and is the case herein. Although specific sequences are provided for the exemplary antibodies disclosed herein, it will be understood that after expression of the protein chains, one to several amino acids at the amino or carboxy termini of the light and / or heavy chains, particularly the lysine residue at the C-terminus of the heavy chain, may be deleted or derivatized in part or all of the molecule.

[0040] The term "epitope" refers to a region on an antigen to which an antibody or extracellular trap segment binds. Epitopes on proteins can be formed from contiguous amino acids or from non-contiguous amino acids juxtaposed by one or more tertiary structural foldings of a protein. Epitopes formed from contiguous amino acids (also known as linear epitopes) are typically retained upon exposure to denaturing solvents, whereas epitopes formed by tertiary structural folding (also known as conformational epitopes) are typically lost upon treatment with denaturing solvents. Epitopes typically contain at least three, more commonly at least five or eight to ten, amino acids in a unique spatial conformation. Methods for determining the spatial conformation of epitopes include, for example, X-ray crystallography and two-dimensional nuclear magnetic resonance. See, for example, Epitope Mapping Protocols, in Methods in Molecular Biology, Vol. 66, Glenn E. See Morris, Ed. (1996).

[0041] Antibodies that recognize the same or overlapping epitopes can be identified by a simple immunoassay showing the ability of one antibody to compete with the binding of another antibody to a target antigen. An antibody's epitope can also be defined by identifying contact residues by X-ray crystallography of the antibody (or Fab fragment) bound to its antigen.

[0042] Alternatively, two antibodies have the same epitope if all amino acid mutations in the antigen that reduce or eliminate binding of one antibody also reduce or eliminate binding of the other. Two antibodies have overlapping epitopes if some amino acid mutations that reduce or eliminate binding of one antibody also reduce or eliminate binding of the other.

[0043] Competition between antibodies is measured by an assay in which a test antibody inhibits the specific binding of a reference antibody to a common antigen (see, e.g., Junghans et al., Cancer Res. 50: 1495, 1990). A test antibody competes with a reference antibody if an excess of the test antibody (e.g., at least 2-fold, 5-fold, 10-fold, 20-fold, or 100-fold) inhibits binding of the reference antibody by at least 50%. In some embodiments, the test antibody inhibits binding of the reference antibody by 75%, 90%, or 99%, as measured in a competitive binding assay. Antibodies identified by a competition assay (competing antibodies) include antibodies that bind to the same epitope as the reference antibody and antibodies that bind to an adjacent epitope that is sufficiently close to the epitope bound by the reference antibody to sterically hinder it.

[0044] As used herein, the term "trap" or similar terms refers to a molecule comprising a binding domain or fragment thereof that enables the molecule to function as a trap and prevents proteins or other molecules from binding to receptors or other binding partners expressed on cells. Various embodiments of trap proteins are known in the art and can be found, for example, in U.S. Patent Application Publication No. 20150376271, the entire contents of which are incorporated herein by reference with respect to various trap embodiments and fusions thereof. In some embodiments, the term "trap" or similar terms refers to a molecule comprising a full-length extracellular region or any portion thereof, or a combination of portions from different molecules, that is capable of antagonizing signaling between at least one molecule and another molecule.

[0045] As used herein, "HTRA1" refers to HtrA serine protease. HTRA1 may refer to, but is not limited to, human HTRA1 (Gene ID: 5654), mouse HTRA1 (Gene ID: 56213), rat HTRA1 (Gene ID: 65164), dog HTRA1 (Gene ID: 477852), chicken HTRA1 (Gene ID: 100857572), or bovine HTRA1 (Gene ID: 282326). In some embodiments, HTRA1 refers to human HTRA1 ("HTRA1"). uHTRA1).

[0046] "aHTRA1" and "anti-HTRA1 antibody" are used interchangeably herein to refer to an antibody that binds to HTRA1, as provided herein.

[0047] As used herein, "potency" with respect to an anti-HTRA1 antibody refers to the ability or degree of inhibition of HTRA1 activity (e.g., the proteolytic activity of HTRA1) when the antibody binds to HTRA1.

[0048] As used herein, the terms "IL-6 antibody-HTRA1 trap fusion," "IL-6 antibody-HTRA1 trap," "Ab IL-6-HTRA1 trap," "anti-IL-6-HTRA1 trap," "HTRA-anti-IL6," "HTRA-anti-IL-6," "HTRA1 trap-anti-IL6 antibody fusion (TAF)," "HTRA1 trap-IL6," "HTRA1IL-6," "IL6-HTRA," or similar or reversed terms (e.g., "HTRA1 trap-IL-6 Ab," "HTRA1 trap-IL-6 antibody fusion," etc.) refer to a fusion of an IL-6 antibody and an HTRA1 trap. When used generically, the order of the two terms is interchangeable. When used specifically, the order of the two terms indicates the relative positions of the components in the construct. The terms "IL-6Ab-HTRA1 trap," "Ab IL-6 HTRA1 trap," or "anti-IL-6 HTRA1 trap," "trap-Ab," anti-IL-6-HTRA, anti-IL6-HTRA1, or other similar or reversed terms (e.g., "HTRA1 trap-IL-6Ab," "HTRA1 trap-IL-6 antibody fusion," etc.) refer to a configuration in which an Ab is fused to the relevant domain of an HTRA1 binding protein to provide an HTRA1 trap.

[0049] As described above, this HTRA1 binding protein section prevents HTRA1 from binding to a substrate. As described herein, the arrangement (order) of the trap section and antibody section can be varied. Therefore, unless otherwise indicated explicitly or by context, the phrases used herein with respect to Ab-trap (or HTRA1 / IL-1 trap, IL-6 / IL-1 trap, etc.) fusions refer to all disclosed embodiments of the positioning of the antibody and trap. When an orientation is specifically indicated, this can be indicated, for example, by stating that the "arrangement" can be one of trap-Ab, trap-IL-1Ab, trap-IL-6Ab, or VEGF-trap Ab-IL-6. Similarly, it is understood that the context of some examples herein indicates a particular orientation or arrangement of the molecules. Either arrangement (either alone or in combination) is expressly contemplated in all discussions of fusion proteins provided herein. Furthermore, due to the order relationship, it is understood that the phrase "IL-6Ab" when used in the context of a fusion protein includes both cases where the antibody is contiguous and on the left side, and where the trap is placed "within" the Ab. Again, the term "Ab" or "antibody" (or other similar term) when used in the context of a fusion protein encompasses all three options unless otherwise specified. In some embodiments, the IL-1 trap is fused to IL-6 or HTRA1 in one of the following ways: at the N-terminus of the heavy chain containing the IL-6 or HTRA1 VH; or between the hinge region and the post-CH1 domain of the heavy chain containing the IL-6 or IL-1 VH. When used in a name to designate an antibody or fragment thereof, there is no distinction between the designations Ab, antibody, "anti," or other similar terms. There is no distinction between the designations "IL-6" or "IL6" or "IL-6." There is no distinction between the designations "IL-1" or "IL1" or "IL-1."

[0050] As used herein, the term "vascular endothelial growth factor (VEGF)" refers to a systemic This refers to the VEGF / PDGF (platelet-derived growth factor) group of signaling proteins in the cysteine-knot superfamily of signaling molecules, which has eight conserved cysteine ​​residues forming a cysteine-knot structure. The VEGF family includes VEGF-A, VEGF-B, VEGF-C, VEGF-D, PlGF (placental growth factor), VEGF-E (Orf-VEGF), and hub svVEGF. With the exception of the last two members, five genes in the VEGF family are present in mammalian genomes, including humans.

[0051] "aVEGF" and "anti-VEGF antibody" are used interchangeably herein to refer to an antibody that binds to VEGF, as provided herein.

[0052] As used herein, "VEGF Trap" or similar terms refer to the VEGF-binding domain (VEGFR1 domain 2, VEGFR2 domain 3). This fragment enables the protein to function as a trap for VEGF and prevent VEGF from binding to VEGF receptors expressed in cells. In some embodiments, the VEGF Trap includes only VEGFR1 domain 2 and VEGFR2 domain 3. Various embodiments of trap proteins are known in the art and can be found, for example, in U.S. Patent Application Publication No. 20150376271, the entire contents of which are incorporated herein by reference with respect to various VEGF trap embodiments (VEGFR proteins or fragments thereof) and fusions thereof. In some embodiments, the term "VEGF Trap" or similar terms refers to the full-length extracellular region or any portion thereof, or a combination of portions from different VEGF receptors that can antagonize signaling between at least one VEGF and a VEGFR.

[0053] As used herein, the term "IL trap" or similar terms refers to the interleukin-binding domains of interleukin receptor proteins and accessory proteins. In some embodiments, it refers to only the extracellular domains of interleukin receptor proteins and accessory proteins, or portions thereof. These fragments enable the protein to function as an IL trap and prevent IL from binding to cell-expressed IL receptors. For example, without limitation, the term "IL-1 trap" refers to the three IG-like domains (D1-D3) of the extracellular domain of the IL1R1 receptor protein and the three IG-like domains (D1-D3) of the extracellular IL1-R1A accessory protein. The transmembrane domain and the intracellular Toll / IL-1R (TIR) ​​domain are not required for IL-1 trap function. These fragments enable the protein to function as an IL-1 trap and prevent IL-1 from binding to cell-expressed IL-1 receptors.

[0054] As used herein, the term "TNFα trap" or similar terms refers to the interleukin-binding domain of TNFR1 and / or TNFR2. In some embodiments, the term refers to the extracellular domain of TNFR1 and / or TNFR2. These fragments enable the protein to function as a TNFα trap and prevent TNFα from binding to cell-expressed TNFα receptors.

[0055] As used herein, the terms "IL-6 antibody-VEGF trap fusion," "IL-6 antibody-VEGF trap," "Ab IL-6-VEGF trap," "anti-IL-6-VEGF trap," "VEGFR-anti-IL6," "VEGFR-anti-IL-6," "VEGF trap-anti-IL6 antibody fusion (TAF)," "VEGF trap-IL6," "VEGFR IL-6," "IL6-VEGFR," or similar or reversed terms (e.g., "VEGF trap-IL-6 Ab," "VEGF trap-IL-6 antibody fusion"). The terms "IL-6Ab-VEGF trap," "Ab IL-6 VEGF trap," "Ab IL-6-trap," "anti-IL-6 VEGF trap," anti-IL-6-VEGFR, anti-IL6-VEGFR, or other similar or reversed terms (e.g., "VEGF trap-IL-6Ab," "VEGF trap-IL-6 antibody fusion," etc.) refer to a fusion of an IL-6 antibody and a VEGF trap. When used generically, the order of the two terms can be interchanged. When used specifically, the order of the two terms indicates the relative positions of the components in the construct. The terms "IL-6Ab-VEGF trap," "Ab IL-6 VEGF trap," or "Ab IL-6-trap," or "anti-IL-6 VEGF trap," anti-IL-6-VEGFR, anti-IL6-VEGFR, or other similar or reversed terms (e.g., "VEGF trap-IL-6Ab," "VEGF trap-IL-6 antibody fusion," etc.) refer to a construct in which an Ab is fused to the relevant domain of a VEGF binding protein to provide a VEGF trap. As described above, this VEGF binding protein section prevents VEGF from binding to the VEGF receptor. As described herein, the arrangement (order) of the trap section and antibody section can be changed. Thus, unless indicated otherwise explicitly or by context, the phrases used herein with respect to Ab-trap (or IL-6 / VEGF trap, etc.) fusions refer to all disclosed embodiments of the positioning of the antibody and trap. When an orientation is specifically indicated, it can be indicated, for example, by stating that the "configuration" can be one of: trap IL-6 Ab, VEGF trap Ab IL-6, VEGF trap Ab IL6.

[0056] The term "patient" includes human and other mammalian subjects receiving prophylactic or therapeutic treatment.

[0057] For the purpose of classifying amino acid substitutions as conservative or non-conservative, amino acids are classified as follows: Group I (amino acids with negatively charged side chains): Asp, Glu; Group II (amino acids with positively charged side chains): Arg, His, Lys; Group III (amino acids with polar, uncharged side chains): Ser, Thr, Cys, Pro, Asn, Gln; Group IV (amino acids with non-polar, alipathic side chains): Gly, Ala, Val, Leu, Met, ILe; and Group V (amino acids with non-polar, aromatic side chains): Phe, Tyr, Trp.

[0058] Percent sequence identity is determined by maximally aligning antibody sequences using Kabat numbering for variable regions and EU numbering for constant regions. After alignment, when a test antibody region (e.g., a full-length mature variable region of a heavy or light chain) is compared with the same region of a reference antibody, the percent sequence identity between the test and reference antibody regions is calculated by dividing the number of positions occupied by the same amino acid in both the test and reference antibody regions by the total number of aligned positions of the two regions (not counting gaps), multiplying by 100 to convert to a percentage. Sequence identity for other sequences can be determined using algorithms such as BESTFIT, FASTA, and TFASTA in Wisconsin Genetics Software Package Release 7.0 (Genetics Computer Group, Inc., 575 Science Dr., Madison, Wisconsin) using default gap parameters, or by inspection and best alignment (i.e., the one resulting in the highest percent sequence similarity over the comparison window). The percentage of sequence identity is calculated by comparing two optimally aligned sequences over a comparison window, determining the number of positions where identical residues occur in both sequences to obtain the number of matched positions, dividing the number of matched positions by the total number of positions in the comparison window (i.e., the window size), and multiplying the result by 100 to calculate the percentage of sequence identity.

[0059] A composition or method "comprising" one or more recited elements is not specifically recited. For example, a composition that includes an antibody may include the antibody alone or in combination with other components.

[0060] The term "antibody-dependent cellular cytotoxicity," or ADCC, is a mechanism for inducing cell death that relies on the interaction of antibody-coated target cells (i.e., antibody-bound cells) with lytic immune cells (also called effector cells). Such effector cells include natural killer cells, monocytes / macrophages, and neutrophils. ADCC is triggered by the interaction between the Fc region of a cell-bound antibody and Fcγ receptors, particularly FcγRI and FcγRIII, on immune effector cells such as neutrophils, macrophages, and natural killer cells. Target cells are eliminated by phagocytosis or lysis, depending on the type of intervening effector cell. Death of antibody-coated target cells occurs as a result of the activity of effector cells.

[0061] The term "opsonization" (also known as "antibody-dependent cellular phagocytosis," or ADCP) refers to the process by which antibody-coated cells are internalized, in whole or in part, by phagocytic immune cells (e.g., macrophages, neutrophils, and dendritic cells) that bind to the immunoglobulin Fc region.

[0062] The term "complement-dependent cytotoxicity" (CDC) refers to a cell death-inducing mechanism in which the Fc effector domain of a target-bound antibody activates a series of enzymatic reactions that ultimately result in the formation of a hole in the target cell membrane. Typically, antigen-antibody complexes, such as those on antibody-coated target cells, bind to and activate complement component C1q, which then activates the complement cascade, leading to target cell death. Complement activation can also result in the deposition of complement components on the target cell surface, which promotes ADCC by binding to complement receptors (e.g., CR3) on leukocytes.

[0063] Humanized antibodies are genetically engineered antibodies in which CDRs from a non-human "donor" antibody are grafted onto human "acceptor" antibody sequences (see, e.g., Queen, U.S. Pat. Nos. 5,530,101 and 5,585,089; Winter, U.S. Pat. No. 5,225,539; Carter, U.S. Pat. No. 6,407,213; Adair, U.S. Pat. Nos. 5,859,205 and 6,881,557; Foote, U.S. Pat. No. 6,881,557). The acceptor antibody sequences can be, for example, mature human antibody sequences, a composite of such sequences, a consensus sequence of human antibody sequences, or germline region sequences. Thus, a humanized antibody is an antibody that has all or substantially some or all of the CDRs from the donor antibody, and all or substantially the variable region framework sequences and constant regions (if present) from human antibody sequences. Similarly, a humanized heavy chain has at least one, two, and usually all three CDRs completely or substantially from a donor antibody heavy chain, and substantially has heavy chain variable region framework sequences and heavy chain constant regions (if present) derived from human heavy chain variable region framework and constant region sequences. Similarly, a humanized light chain has at least one, two, and usually all three CDRs completely or substantially from a donor antibody light chain, and substantially has light chain variable region framework sequences and light chain constant regions (if present) derived from human light chain variable region framework and constant region sequences. Other than nanobodies and dAbs, humanized antibodies include humanized heavy chains and humanized light chains. CDRs in a humanized antibody are substantially derived from corresponding CDRs in a non-human antibody if at least 85%, 90%, 95%, or 100% of the corresponding residues (as defined by Kabat) are identical between the respective CDRs. The antibody chain variable region framework sequence or antibody chain constant region is substantially derived from a human variable region framework sequence or human constant region, respectively, according to Kabat. A sequence is a sequence where at least 85%, 90%, 95%, or 100% of the corresponding residues are identical, as defined by the formula:

[0064] Although humanized antibodies often incorporate all six CDRs (as defined by Kabat) from a murine antibody, humanized antibodies can also be made using fewer than all CDRs (e.g., at least three, four, or five CDRs from a murine antibody) (see, e.g., De Pascalis R, Iwahashi M, Tamura M, et al. 2002. Grafting “Abbreviated” Complementary-Determining Regions Containing Specificity-Determining Residues Essential for Ligand Contact to Engineer a Less Immunogenic Humanized Monoclonal Antibody. J Immunol. 169:3076-3084; Vajdos FF, Adams CW, Breece TN, Presta LG, de Vos AM, Sidhu, SS. 2002. Comprehensive functional maps of the antigen-binding site of an anti-ErbB2 antibody obtained with shotgun scanning mutagenesis. J Immunol. 169:3076-3084). Mol Biol. 320: 415-428; Iwahashi M, MILenic DE, Padlan EA, et al. 1999. CDR substitutions of a humanized monoclonal antibody (CC49): Contributions of individual CDRs to antigen binding and immunogenicity. Mol Immunol. 36:1079-1091; Tamura M, MILenic DE, Iwahashi M, et al. 2000. Structural correlates of an anticarcinoma antibody: Identification of specificity-determining regions (SDRs) and development of a minimally immunogenic antibody variant by retention of SDRs only. J Immunol. 164:1432-1441).

[0065] Chimeric antibodies are antibodies in which the mature variable regions of the light and heavy chains of a non-human antibody (e.g., murine) are combined with human light and heavy chain constant regions. Such antibodies substantially or completely retain the binding specificity of the murine antibody and contain approximately two-thirds human sequences.

[0066] As used herein, the term "Knobs-Into-Holes" (KIH) can refer to a strategy for pairing the heavy chain portions of the constant regions in antibodies and fragments thereof. The "knobs" portion is created by substituting a smaller amino acid for a larger one. For example, in some embodiments, the knob comprises the knob in SEQ ID NO: 65. The knob fits into the "hole," which is created by substituting a larger amino acid for a smaller one. For example, in some embodiments, the hole comprises the hole in SEQ ID NO: 66. Linking the "knobs" to the "hole" is a disulfide bond between each chain.

[0067] A veneered antibody is a type of humanized antibody that retains some, usually all, of the CDRs and some non-human variable region framework residues of a non-human antibody, but replaces other variable region framework residues that may contribute to B-cell or T-cell epitopes, e.g., exposed residues, with residues from the corresponding positions in a human antibody sequence (Padlan EA. 1991. A possible process (These modifications are intended to reduce the immunogenicity of antibody variable regions while preserving their ligand-binding properties. Mol. Immunol. 28:489-98). The result is an antibody in which the CDRs are derived entirely or substantially from a non-human antibody and the variable region framework of the non-human antibody has been made more human-like by substitutions. Human antibodies can be isolated from humans or obtained by expression of human immunoglobulin genes (e.g., in transgenic mice, in vitro, or by phage display).Methods for producing human antibodies include the following: Ostberg L, Pursch E. 1983. Human x (mouse x human) hybridomas stably producing human antibodies. Hybridoma 2:361-367; Ostberg, U.S. Pat. No. 4,634,664; and the trioma method of Engleman et al., U.S. Pat. No. 4,634,666; the use of transgenic mice containing human immunoglobulin genes (see, e.g., Lonberg et al., 1983). al., WO 93 / 12227 (1993); U.S. Pat. Nos. 5,877,397, 5,874,299, 5,814,318, 5,789,650, 5,770,429, 5,661,016, 5,633,425, 5,625,126, 5,569,825, 5,545,806, Nature 148, 1547-1553 (1994), Nature Biotechnology 14, 826 (1996), Kucherlapati, WO 91 / 10741 (1991), as well as phage display methods (e.g., Dower et al. See, e.g., McCafferty et al., WO 91 / 17271, and McCafferty et al., WO 92 / 01047, U.S. Pat. Nos. 5,877,218, 5,871,907, 5,858,657, 5,837,242, 5,733,743, and 5,565,332.

[0068] A "pharmaceutically acceptable excipient" refers to an excipient that can be included in a composition, does not cause significant adverse toxic effects in patients, and has been or can be approved by the FDA for therapeutic use, particularly in humans. Non-limiting examples of pharmaceutically acceptable excipients include water, NaCl, normal saline, lactated Ringer's solution, normal sucrose, normal glucose, etc.

[0069] A "therapeutic protein" is administered in an effective regimen, meaning that the dosage, route of administration, and frequency of administration delay the onset of the disorder, reduce the severity of the disorder, inhibit further deterioration of the disorder, and / or ameliorate at least one sign or symptom of the disorder. If the patient already has the disorder, the regimen may be referred to as a therapeutically effective regimen. In some embodiments, the disorder includes diabetic retinopathy, early, intermediate, or advanced age-related macular degeneration (AMD), retinopathy of prematurity (ROP), dry AMD, geographic atrophy, wet (neovascular) AMD, polypoidal choroidal vasculopathy, ocular inflammation, HTRA1-related disorders, and / or IL-1-related disorders, scleritis, diabetic macular edema, diabetic retinopathy, wet age-related macular degeneration, uveitis, non-infectious uveitis, macular edema associated with uveitis, cytokine release syndrome following CAR-T or similar immuno-oncology therapy, and / or suppression of induction of IL-6 expression observed following treatment with anti-PD-1 / PD-L1 molecules, cancer, brain edema in glioblastoma, IL-6-related disorders, and / or VEGF-related disorders. In some embodiments, the disorder includes ocular inflammation In some embodiments, the disorder is ocular inflammation. Inflammation. If a patient is at increased risk for a disorder compared to the general population but has not yet experienced symptoms, the regimen may be referred to as a prophylactically effective regimen. In some instances, therapeutic or prophylactic efficacy may be observed in an individual patient compared to historical controls or previous experience in the same patient. In other instances, therapeutic or prophylactic efficacy may be demonstrated in preclinical or clinical studies in a treated patient population compared to a control untreated patient population.

[0070] The "biological half-life" of a substance is a pharmacokinetic parameter that defines the time required for half of the substance to be eliminated from a tissue or organism after introduction of that substance.

[0071] "BCVA" indicates best corrected visual acuity.

[0072] "OCT-A" indicates OCT angiography.

[0073] "SD-OCT" stands for Spectral Domain Optical Coherence Tomography.

[0074] An "angiogenic disorder" is a disorder or condition characterized by altered, dysregulated, or unregulated angiogenesis. Examples of angiogenic disorders include malignant transformation (e.g., cancer), and ocular angiogenic disorders, including diabetic retinopathy and age-related macular degeneration.

[0075] An "ocular neovascular" disorder is one characterized by altered, dysregulated, or unregulated angiogenesis in a patient's eye. Such disorders include optic nerve head neovascularization, iris neovascularization, retinal neovascularization, choroidal neovascularization, corneal neovascularization, vitreous neovascularization, glaucoma, pannus, pterygium, macular edema, diabetic retinopathy, diabetic macular edema, vascular retinopathy, retinal degeneration, uveitis, non-infectious uveitis, inflammatory diseases of the retina, and proliferative vitreoretinopathy.

[0076] Multivalent interleukin (IL) trap-antibody fusions Some embodiments herein relate to a multivalent interleukin (IL) trap-antibody fusion or a multivalent IL trap-Fab fusion comprising an IL trap and an antibody or fragment thereof, wherein the antibody or fragment thereof comprises a heavy chain variable region (VH) comprising three complementarity-determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3; the IL trap comprises an IL receptor and an IL accessory protein; the IL trap and the antibody are connected in series by a linker; the IL trap-antibody fusion or trap-Fab fusion comprises both an IL-binding site and an antigen-binding site; and the IL-binding site and the antigen-binding site are located at separate positions on the trap-antibody fusion or trap-Fab fusion.

[0077] Some embodiments herein relate to multivalent interleukin (IL) trap-antibody fusions or multivalent IL trap-Fab fusions. In some embodiments, the multivalent IL trap-antibody fusions or trap-Fab fusions comprise an IL trap and an antibody or Fab fragment; the IL trap comprises an IL receptor and an IL accessory protein; the antibody or Fab fragment comprises a heavy chain variable region (VH) comprising three complementarity-determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3; the interleukin trap and antibody are connected in tandem by a linker; the interleukin trap-antibody fusion comprises both an IL-binding site and an antigen-binding site; binding of the IL trap-antibody fusion to an IL inhibits IL signaling; and binding of the IL trap-antibody fusion to an antigen inhibits antigen activity.

[0078] Figure 1 is a representative illustration of several embodiments of multivalent interleukin (IL) trap-antibody fusions. In some embodiments, the IL trap-antibody fusion comprises a homodimeric receptor. In some embodiments, the IL trap-antibody fusion comprises a heterodimeric fusion. In some embodiments, the IL receptor protein and accessory protein are linked to the heavy and light chains of the same antibody arm. In some embodiments, the IL receptor protein and accessory protein.

[0079] In some embodiments, a multivalent interleukin (IL) trap-antibody 100 or trap-Fab fusion 106 is disclosed. In some embodiments, the multivalent IL trap-antibody fusion comprises an IL trap 101 and an antibody or fragment thereof 102. In some embodiments, the antibody or fragment thereof comprises a heavy chain variable region (VH) comprising three complementarity-determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody fragment comprises a Fab fragment. In some embodiments, the IL trap 104 comprises an IL receptor and an IL accessory protein. In some embodiments, the IL trap 101 and the antibody 102 or Fab fragment are connected in tandem by a linker 103. In some embodiments, the length of the linker is selected so that the linker's ability to promote a desired function or property of the multivalent IL trap-antibody fusion is enhanced. In some embodiments, the IL trap-antibody 100 or trap-Fab fusion 106 comprises both an IL binding site 104 and an antigen binding site 105. In some embodiments, the IL binding site and the antigen binding site are located at separate locations on the trap-antibody fusion or trap-Fab fusion. For example, in some embodiments, the IL binding site is located on an IL trap linked to an antibody or Fab fragment, while the antigen binding site is located on an antibody arm. In some embodiments, the IL binding site is linked to the same antibody arm that contains the antigen binding site. In some embodiments, the IL binding site is linked to the opposite antibody arm from the antigen binding site. In some embodiments, binding of the IL trap-antibody fusion to an IL inhibits IL signaling. In some embodiments, binding of the IL trap-antibody fusion to an antigen inhibits antigen activity. In some embodiments, the antigen binding site and the IL binding site are tandemly located on the same antibody arm or the same Fab fragment arm. In some embodiments, the interleukin trap-antibody-heterodimeric fusion or interleukin trap-Fab fusion is multivalent.

[0080] Figure 2 is a representative illustration of several embodiments of a multivalent interleukin (IL) trap-antibody fusion or IL trap-Fab binding to an IL and an antigen. In some embodiments, the IL trap-antibody fusion comprises a homodimeric receptor. In some embodiments, the IL trap-antibody fusion comprises a heterodimeric fusion. In some embodiments, the IL receptor protein and accessory protein are linked to the heavy and light chains of the same antibody arm. In some embodiments, the IL receptor protein and accessory protein are linked in tandem to the heavy chain, the light chain, or both of one or both antibody arms.

[0081] In some embodiments, a multivalent interleukin (IL) trap-antibody fusion 200 or a multivalent IL trap-Fab fusion 208 is provided. In some embodiments, the multivalent IL trap-antibody fusion 200 or the multivalent IL trap-Fab fusion 208 comprises an IL trap 201 and an antibody or fragment thereof 202. In some embodiments, the antibody or fragment thereof comprises a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3. In some embodiments, In some embodiments, the antibody fragment comprises a Fab fragment. In some embodiments, the IL trap 201 comprises an IL receptor and an IL accessory protein. In some embodiments, the IL trap 201 and antibody 202 are connected in series by a linker 203. In some embodiments, the length of the linker is selected so that the linker's ability to promote a desired function or property of the multivalent IL trap-antibody fusion is enhanced. In some embodiments, the IL trap-antibody fusion 200 comprises both an IL binding site 204 and an antigen binding site 205. In some embodiments, the IL binding site and the antigen binding site are located at separate locations on the trap-antibody fusion or trap-Fab fusion. For example, in some embodiments, the IL binding site is located on the IL trap linked to the antibody, while the antigen binding site is located on an antibody arm. In some embodiments, the IL binding site is linked to the same antibody arm that contains the antigen binding site. In some embodiments, the IL binding site is linked to the opposite antibody arm from the antigen binding site. In some embodiments, binding of the IL trap-antibody fusion to IL206 inhibits IL signaling. In some embodiments, binding of the IL trap-antibody fusion to the antigen 207 inhibits antigen activity. In some embodiments, the antigen binding site and the IL binding site are in tandem on the same antibody arm. In some embodiments, binding of the IL trap-antibody fusion to the IL inhibits IL signaling. In some embodiments, binding of the IL trap-antibody fusion to the antigen inhibits antigen activity. In some embodiments, the interleukin trap-antibody-heterodimeric fusion is multivalent.

[0082] FIG. 16 is an illustrative illustration of several embodiments of multivalent interleukin (IL) trap-antibody fusions that are conjugated to polymers.

[0083] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an antibody complex. In some embodiments, the antibody complex comprises an anti-HTRA1 antibody complex. In some embodiments, the trap-antibody fusion comprises an antibody complex and a homodimeric receptor. In some embodiments, the trap-antibody fusion comprises an antibody complex and a heterodimeric receptor.

[0084] Some aspects of the present disclosure relate to methods of inhibiting interleukin signaling in a subject. In some embodiments, the method comprises administering an interleukin trap-antibody heterodimeric fusion. In some embodiments, the heterodimeric fusion comprises an IL trap, an antibody, an IL-binding site, and an antigen-binding site; binding of the IL trap-antibody heterodimeric fusion to an IL inhibits IL signaling; and binding of the IL trap-antibody heterodimeric fusion to an antigen inhibits antigen activity.

[0085] Some aspects of the present disclosure relate to methods for inhibiting interleukin signaling in a subject. In some embodiments, the methods include administering an interleukin trap-antibody heterodimeric fusion or an interleukin trap-Fab fusion. In some embodiments, the heterodimeric fusion comprises an IL trap and an antibody or a Fab fragment; the antibody or Fab fragment comprises a heavy chain variable region (VH) comprising three complementarity-determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3; the IL trap-antibody heterodimeric fusion comprises an IL-binding site and an antigen-binding site; binding of the IL trap-antibody heterodimeric fusion or IL trap-Fab fusion to an IL inhibits IL signaling; and binding of the IL trap-antibody heterodimeric fusion or IL trap-Fab fusion to an antigen inhibits antigen activity.

[0086] FIG. 3 is a flow chart and representative illustration of some embodiments of methods for inhibiting interleukin signaling.

[0087] In some embodiments, a method 300 of inhibiting interleukin signaling in a subject is disclosed. In some embodiments, the method includes administering 301 an interleukin trap-antibody-heterodimeric fusion or an interleukin trap-Fab fusion. In some embodiments, the heterodimeric fusion includes an IL trap 303. In some embodiments, the IL trap includes a receptor protein. In some embodiments, the IL trap includes an effector protein. In some embodiments, the interleukin trap-antibody-heterodimeric fusion or the interleukin trap-Fab fusion includes an antibody 304. In some embodiments, the IL trap includes an effector protein. In some embodiments, the interleukin trap-antibody-heterodimeric fusion or the interleukin trap-Fab fusion includes a Fab fragment 309. In some embodiments, the antibody or Fab fragment comprises a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the IL trap-antibody-heterodimeric fusion or IL trap-Fab fusion comprises an IL binding site 306 and an antigen binding site 307. In some embodiments, binding of the IL trap-antibody-heterodimeric fusion or IL trap-Fab fusion to an IL inhibits IL signaling. In some embodiments, binding of the IL trap-antibody-heterodimeric fusion or IL trap-Fab fusion to an antigen inhibits antigen activity. In some embodiments, the interleukin trap-antibody-heterodimeric fusion is multivalent.

[0088] In some embodiments, the interleukin trap-antibody-heterodimeric fusion or interleukin trap-Fab fusion is multivalent, ie, the interleukin trap-antibody-heterodimeric fusion or trap-Fab is monovalent, bivalent, trivalent, tetravalent, pentavalent, hexavalent, heptavalent, or octavalent.

[0089] In some embodiments, the interleukin trap-antibody-heterodimeric fusion comprises two IL traps and one antibody or two Fab fragments. In some embodiments, the trap-antibody fusion is bispecific. In some embodiments, the antibody comprises an anti-HTRA1 antibody or fragment thereof. In some embodiments, the IL trap comprises an IL1R1 receptor protein. In some embodiments, the IL trap comprises an IL1R1A accessory protein. In some embodiments, the IL trap comprises an IL1R1 receptor protein and an IL1R1A accessory protein. In some embodiments, the IL trap comprises an IL1R1 receptor protein and / or an IL1R1A accessory protein.

[0090] In some embodiments, the interleukin trap-antibody-heterodimeric fusion or interleukin trap-Fab fusion is conjugated to a polymer. In some embodiments, the antibody conjugate has the structure of Formula (I): [ka]

[0091] where each heavy chain of the anti-HTRA1 antibody is represented by the letter H and each light chain of the anti-HTRA1 antibody is represented by the letter L; the polymer is attached to the anti-HTRA1 antibody via the sulfhydryl of C443 (EU numbering), which is shown on one of the heavy chains; and PC is where the wavy line indicates the point of attachment to the rest of the polymer; X is a) -OR where R is -H, methyl, ethyl, propyl, or isopropyl, b) H, or c) any halogen, including -Br, -Cl, or -I; i) n1, n2, n3, n4, n5, n6, n7, n8, and n9 are the same or different and are integers from 0 to 3000; or ii) n1, n2, n3, n4, n5, n6, n7, n8, and n9 are the same or different such that the sum of n1, n2, n3, n4, n5, n6, n7, n8, and n9 is 2500±20%. In some embodiments, the sum of n1, n2, n3, n4, n5, n6, n7, n8, and n9 is about 1500 to about 3500±about 10% to about 20%. In some embodiments, X is -OR (wherein R is a sugar, an aminoalkyl, a mono-substituted, poly-substituted, or unsubstituted variant of the following residues: saturated alkyl of 1 to 24 carbon atoms, unsaturated alkenyl of 2 to 24 carbon atoms, or alkynyl of 2 to 24 carbon atoms, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarbonyloxy). ), nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and alkyl halides including polyhalogenated alkyls), —CO—O—R7, carbonyl-CCO—R7, —CO—NR8R9, —(CH2)n-COOR7, —CO—(CH)n-COOR7, —(CH2)n-NR8R9, ester, alkoxycarbonyl, aryloxycarbonyl (n is an integer from 1 to 6, and each R7, R8, and R9 is independently selected from the group consisting of a hydrogen atom, a halogen atom, a mono-substituted variant, a poly-substituted variant, or an unsubstituted variant of the following residues: and alkyl halides including polyhalogenated alkyls, 5-membered rings, and 6-membered rings.

[0092] In some embodiments, the antibody conjugate has the structure of formula (II): [ka]

[0093] During the ceremony,

[0094] "n." is an integer between 1 and 50, and "ni" is an integer between 1 and 50;

[0095] Each heavy chain of the anti-HTRA1 antibody is represented by the letter H, and each light chain of the anti-HTRA1 antibody is represented by the letter L; the polymer is attached to the anti-HTRA1 antibody via the sulfhydryl of C443 (EU numbering), which is shown on one of the heavy chains; PC is where the wavy line indicates the point of attachment to the rest of the polymer; X is a) -OR where R is -H, methyl, ethyl, propyl, isopropyl, b) H, or c) any halogen, including -Br, -Cl, or -I; i) n1, n2, n3, n4, n5, n6, n7, n8, and n9 are the same or different and are integers from 0 to 3000; or ii) n1, n2, n3, n4, n5, n6, n7, n8, and n9 are the same or different such that the sum of n1, n2, n3, n4, n5, n6, n7, n8, and n9 is 2500±20%.

[0096] In some embodiments, the half-life of an anti-HTRA1 antibody is extended by the attachment of a "half-life ("half life") extending moiety" or "half-life ("half life") extending group." Half-life extending moieties include peptides and proteins that can be expressed in-frame with (or optionally chemically conjugated to) the biologic, as well as various polymers that can be attached or conjugated to one or more amino acid side chain or terminal functional groups, such as -SH, -OH, -COOH, -CONH, -NH, or one or more N- and / or O-glycan structures. Half-life extending moieties typically serve to extend the in vivo circulatory half-life of a biologic agent.

[0097] Suitable peptide / protein half-life extending moieties include, but are not limited to, Fc fusions, human serum albumin (HAS) fusions, carboxy-terminal peptide (CTP) fusions, non-perfect repeat peptide sequence (XTEN) fusions via genetic fusion, elastin-like peptide (ELPylation) (Production and purification of a recombinant elastomeric polypeptide, G-(VPGVG)19-VPGV, from Escherichia coli), human transferrin fusions, proline-alanine-serine (PASylation), homo-amino acid polymers (HAPylation), and gelatin-like protein (GLK) fusions.

[0098] Examples of polymeric half-life extending moieties include polyethylene glycol (PEG), branched PEG, PolyPEG® (Warwick Effect Polymers; Coventry, UK), polysialic acid (PSA), starch, hydroxyethyl starch (HES), hydroxyalkyl starch (HAS), carbohydrates, polysaccharides, pullulane, chitosan, hyaluronic acid, chondroitin sulfate, dermatan sulfate, dextran, carboxymethyl-dextran, polyalkylene oxide (PAO), polyalkylene glycol (PAG), polypropylene glycol (PPG), polyoxazoline, polyacryloylmorpholine, polyvinyl alcohol (PVA), polycarboxylate, polyvinylpyrrolidone, polyphosphazene, polyoxazoline, polyethylene maleic anhydride copolymer, polystyrene maleic anhydride copolymer, poly(1-hydroxymethyethylene hydroxymethylformaldehyde), ... hydroxymethylformal) (PHF), zwitterionic polymers, phosphorylcholine-containing polymers, and polymers containing MPC, poly(Gly x -Ser y ), hyaluronic acid (HA), heparosan polymer (HEP), Fleximer, dextran, and polysialic acid (PSA).

[0099] In one embodiment, half-life extending moieties may be conjugated to antibodies via the free amino groups of the protein using N-hydroxysuccinimide (NHS) esters. Reagents intended for conjugation to amine groups may react randomly with the ε-amine groups of lysines, the α-amine group of the N-terminal amino acid, and the δ-amine group of histidine.

[0100] In some embodiments, half-life extending moieties are attached to one or more free SH groups using any suitable thiol-reactive chemistry (including, but not limited to, maleimide chemistry), or by attaching a polymeric hydrazide or a polymeric amine to a pre-oxidized antibody carbohydrate. In some embodiments, maleimide coupling is used. In some embodiments, coupling occurs at a naturally occurring or engineered cysteine.

[0101] In some embodiments, the polymer is covalently attached to a cysteine ​​residue introduced into the anti-HTRA1 antibody by site-directed mutagenesis or to a non-native cysteine. In some embodiments, the cysteine ​​residue is one utilized in the Fc portion of the antibody. In some embodiments, the non-native cysteine ​​residue is one present in the Fc portion of the antibody. In some embodiments, sites for introducing cysteine ​​residues into the Fc region are provided in WO 2013 / 093809, U.S. Pat. No. 7,521,541, WO 2008 / 020827, U.S. Pat. No. 8,008,453, U.S. Pat. No. 8,455,622, and U.S. Patent Application Publication No. 2012 / 0213705, which are incorporated herein by reference for all purposes. In some embodiments, the cysteine ​​mutations are Q347C (EU numbering) and L443C, which refer to the human IgG heavy chain in EU numbering.

[0102] In some embodiments, a conjugate of an antibody and a high molecular weight polymer that acts as a half-life extender is provided. In some embodiments, the conjugate comprises an antibody bound to a zwitterionic polymer, the polymer being formed from one or more monomeric units, at least one of the monomeric units having a zwitterionic group. In some embodiments, the zwitterionic group is phosphorylcholine.

[0103] In some embodiments, one of the monomer units is HEMA-PC. In some embodiments, the polymer is synthesized from a single monomer that is HEMA-PC.

[0104] In some embodiments, some antibody conjugates have two, three, or more polymer arms, and the monomer is HEMA-PC. In some embodiments, the conjugates have two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve polymer arms, and the monomer is HEMA-PC. In some embodiments, the conjugates have three, six, or nine arms. In some embodiments, the conjugates have nine arms.

[0105] In some embodiments, the polymer-antibody conjugate has a polymer portion having a molecular weight of 100,000 Da to 1,500,000 Da. In some embodiments, the conjugate has a polymer portion having a molecular weight of 500,000 Da to 1,000,000 Da. In some embodiments, the conjugate has a polymer portion having a molecular weight of 600,000 Da to 800,000 Da. In some embodiments, the conjugate has a polymer portion having a molecular weight of 600,000 Da to 850,000 Da and has 9 arms. When molecular weight is indicated for an antibody conjugated to a polymer, it refers to the molecular weight of the protein (including any carbohydrate chains attached thereto) plus the molecular weight of the polymer.

[0106] In some embodiments, the anti-HTRA1 antibody comprises a HEMA-PC polymer having a molecular weight, as measured by Mw, of about 100 kDa to about 1650 kDa. In some embodiments, the molecular weight of the polymer, as measured by Mw, is about 500 kDa to about 1000 kDa. In some embodiments, the molecular weight of the polymer, as measured by Mw, is about 600 kDa to about 900 kDa. In some embodiments, the molecular weight of the polymer, as measured by Mw, is 750 kDa ± 15%.

[0107] In some embodiments, the interleukin trap-antibody-heterodimeric fusion further comprises a signal peptide. In some embodiments, the interleukin trap-antibody-heterodimeric fusion further comprises a signal peptide that is the signal peptide in any one of SEQ ID NOs: 16-23. In some embodiments, the signal The signal peptides include those of SEQ ID NO: 16 (MYRMQLLSCIALSLALVTNS), SEQ ID NO: 17 (MTLLWCVVSLYFYGILQSDA), SEQ ID NO: 18 (MKVLLRLICFIALLISSLEAD), SEQ ID NO: 19 (MLRLYVLVMGVSAFTLQPAA), SEQ ID NO: 20 (METDTLLLWVLLLWVPGSTG), SEQ ID NO: 21 (MGFWILAILTILMYSTAAKF), SEQ ID NO: 22 (MLAVGCALLAALLAAPGAA), and SEQ ID NO: 23 (MLTLQTWLVQALFIFLTTESTG). In some embodiments, the interleukin trap-antibody-heterodimer fusion further comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to the signal peptide in any one of SEQ ID NOs: 16-23.

[0108] In some embodiments, the interleukin trap-antibody-heterodimeric fusion binds the IL and the antigen simultaneously. In some embodiments, the interleukin trap-antibody-heterodimeric fusion binds the IL and the antigen sequentially.

[0109] In some embodiments, the interleukin trap-antibody-heterodimeric fusion comprises an IL trap with an IL binding affinity of about 0.01 pM, about 0.05 pM, about 0.1 pM, about 0.2 pM, about 0.25 pM, about 0.3 pM, about 0.4 pM, about 0.5 pM, about 0.6 pM, about 0.7 pM, about 0.8 pM, about 0.9 pM, about 1 pM, about 5 pM, about 10 pM, about 15 pM, about 20 pM, about 25 pM, about 30 pM, about 40 pM, about 50 pM, about 60 pM, about 70 pM, about 75 pM, about 80 pM, about 90 pM, about 95, or about 100 pM, or a binding affinity within a range defined by any two of the above values.For example, in some embodiments, the interleukin trap-antibody-heterodimeric fusion comprises an IL trap with an IL binding affinity between or below the following values: about 0.01 pM to about 100 pM, about 0.01 pM to about 75 pM, about 0.01 pM to about 50 pM, about 0.01 pM to about 25 pM, about 0.01 pM to about 10 pM, about 0.01 pM to about 5 pM, about 0.01 pM to about 1 pM, about 0.01 pM M ~ about 0.05pM, about 0.05pM to about 100pM, about 0.05pM to about 75pM, about 0.05pM to about 50pM, about 0.05pM to about 25pM, about 0.05pM to about 10pM, about 0.05pM to about 5p M, about 0.05pM to about 0.1pM, about 0.1pM to about 100pM, about 0.1pM to about 75pM, about 0.1pM to about 50pM, about 0.1pM to about 25pM, about 0.1pM to about 10pM, about 0.1pM to about 5 pM, about 0.1 pM to about 1 pM, about 0.1 pM to about 0.5 pM, about 0.5 pM to about 100 pM, about 0.5 pM to about 75 pM, about 0.5 pM to about 50 pM, about 0.5 pM to about 25 pM, about 0.5 pM to about 10 pM, about 0.5 pM to about 5 pM, about 0.5 pM to about 1 pM, about 1 pM to about 100 pM, about 1 pM to about 75 pM, about 1 pM to about 50 pM, about 1 pM to about 25 pM, about 1 pM to about 10 pM, about 1 pM to about 5 pM , about 5 pM to about 100 pM, about 5 pM to about 75 pM, about 5 pM to about 50 pM, about 5 pM to about 25 pM, about 5 pM to about 10 pM, about 10 pM to about 100 pM, about 10 pM to about 75 pM, about 10 pM to about 50 pM, about 10 pM to about 25 pM, about 25 pM to about 100 pM, about 25 pM to about 75 pM, about 25 pM to about 50 pM, about 50 pM to about 100 pM, about 50 pM to about 75 pM, or about 75 pM to about 100 pM.

[0110] In some embodiments, the interleukin trap-antibody-heterodimeric fusion comprises an antibody with an antigen-binding affinity of about 50 pM to 500 pM. In some embodiments, the interleukin trap-antibody-heterodimeric fusion is at about 50 pM, about 55 pM, about 60 pM, about 65 pM, about 70 pM, about 75 pM, about 80 pM, about 85 pM, about 90 pM, about 95 pM, about 100 pM, about 105 pM, about 110 pM, about 115 pM, about 120 pM, about 125 pM, about 130 pM, about 135 pM, about 140 pM, about 145 pM, about 150 pM, about 155 pM, about 160 pM, about 165 pM, about 170 pM, about 175 pM, about 180 pM, about 185 pM, about 190 pM, about 195 pM, about 200 pM, about 205pM, approx. 210pM, approx. 215pM, approx. 220pM, approx. 225pM, approx. 230pM, approx. 235pM, approx. 240pM, approx. 245p M, about 250pM, about 255pM, about 260pM, about 265pM, about 270pM, about 275pM, about 280pM, about 285pM, about 29 0pM, approx. 295pM, approx. 300pM, approx. 305pM, approx. 310pM, approx. 315pM, approx. 320pM, approx. 325pM, approx. 330pM, approx. 335pM, approx. 340pM, approx. 345pM, approx. 350pM, approx. 355pM, approx. 360pM, approx. 365pM, approx. 370pM, approx. 375p M, about 380 pM, about 385 pM, about 390 pM, about 395 pM, about 400 pM, about 405 pM, about 410 pM, about 415 pM, about 420 pM, about 425 pM, about 430 pM, about 435 pM, about 440 pM, about 445 pM, about 450 pM, about 455 pM, about 460 pM, about 465 pM, about 470 pM, about 475 pM, about 480 pM, about 485 pM, about 490 pM, about 495 pM, or about 500 pM, or a binding affinity within a range defined by any two of the above values ​​or less than or equal to any specified value. For example, in some embodiments, the interleukin trap-antibody-heterodimeric fusion comprises an antibody with an antigen binding affinity between or below the following values: about 50 pM to about 500 pM, about 50 pM to about 450 pM, about 50 pM to about 300 pM, about 50 pM to about 250 pM, about 50 pM to about 200 pM, about 50 pM to about 150 pM, about 50 pM to about 100 pM, about 100 pM to about 500 pM, about 100 pM to about 4 50 pM, about 100 pM to about 400 pM, about 100 pM to about 350 pM, about 100 pM to about 300 pM, about 100 pM to about 250 pM, about 100 pM to about 200 pM, about 200 pM to about 500 pM, about 200 pM to about 400 pM, about 200 pM to about 300 pM, about 250 pM to about 500 pM, about 250 pM to about 400 pM, about 300 pM to about 500 pM, about 300 pM to about 400 pM, and about 400 pM to about 500 pM.

[0111] In some embodiments, the interleukin trap-antibody heterodimeric fusion comprises an IL trap having an IL-binding affinity of about 0.01 pM, about 0.05 pM, about 0.1 pM, about 0.2 pM, about 0.25 pM, about 0.3 pM, about 0.4 pM, about 0.5 pM, about 0.6 pM, about 0.7 pM, about 0.8 pM, about 0.9 pM, about 1 pM, about 5 pM, about 10 pM, about 15 pM, about 20 pM, about 25 pM, about 30 pM, about 40 pM, about 50 pM, about 60 pM, about 70 pM, about 75 pM, about 80 pM, about 90 pM, about 95 pM, or about 100 pM, or an IL-binding affinity within a range defined by any two of the above values, and an antibody having an antigen-binding affinity of about 50 pM to about 500 pM.For example, in some embodiments, the interleukin trap-antibody-heterodimeric fusion has an IL binding affinity of at or below the following values: about 0.01 pM, about 0.05 pM, about 0.1 pM, about 0.2 pM, about 0.25 pM, about 0.3 pM, about 0.4 pM, about 0.5 pM, about 0.6 pM, about 0.7 pM, about 0.8 pM, about 0.9 pM, about 1 pM, about 5 pM, about 10 pM, about 15 pM, about 20 pM, about 25 pM, about 30 pM, IL traps having about 40 pM, about 50 pM, about 60 pM, about 70 pM, about 75 pM, about 80 pM, about 90 pM, about 95 pM, or about 100 pM, and IL traps having about 50 pM, about 55 pM, about 60 pM, about 65 pM, about 70 pM, about 75 pM, about 80 pM, about 85 pM, about 90 pM, about 95 pM, about 100 pM, about 105 pM, about 110 pM, about 115 pM, about 120 pM, about 125 pM, about 130 pM, about 135 pM, about 140 pM , about 145pM, about 150pM, about 155pM, about 160pM, about 165pM, about 170pM, about 175pM, about 180pM, about 185pM, about 190pM, about 195pM, about 200pM, about 205pM, about 210 pM, approximately 215pM, approximately 220pM, approximately 225pM, approximately 230pM, approximately 235pM, approximately 240pM, approximately 245pM, approximately 250pM, approximately 255pM, approximately 260pM, approximately 265pM, approximately 270pM, approximately 275pM, approximately 2 80pM, approximately 285pM, approximately 290pM, approximately 295pM, approximately 300pM, approximately 305pM, approximately 310pM, approximately 315pM, approximately 320pM, approximately 325pM, approximately 330pM, approximately 335pM, approximately 340pM, approximately 345pM, About 350pM, about 355pM, about 360pM, about 365pM, about 370pM, about 375pM, about 380pM, about 385pM, about 390pM, about 395pM, about 400pM, about 405pM, about 410pM, about 415. and antibodies having an antigen-binding affinity of about 420 pM, about 425 pM, about 430 pM, about 435 pM, about 440 pM, about 445 pM, about 450 pM, about 455 pM, about 460 pM, about 465 pM, about 470 pM, about 475 pM, about 480 pM, about 485 pM, about 490 pM, about 495 pM, or about 500 pM, or a binding affinity that is within a range defined by any two of the above values. For example, in some embodiments, the antibody has an antigen-binding affinity between or below the following values: about 50 pM to about 500 pM, about 50 pM to about 450 pM, about 50 pM to about 400 pM, about 50 pM to about 350 pM, about 50 pM to about 300 pM, about 50 pM to about 250 pM, about 50 pM to about 200 pM, about 50 pM to about 150 pM, about 50 pM to about 100 pM, about 100 pM to about 500 pM, about 100 pM to about 450 pM, about 100 pM to about 50 ... pM to about 400 pM, about 100 pM to about 350 pM, about 100 pM to about 300 pM, about 100 pM to about 250 pM, about 100 pM to about 200 pM, about 200 pM to about 500 pM, about 200 pM to about 450 pM, about 200 pM to about 400 pM, about 200 pM to about 350 pM, about 200 pM to about 300 pM, about 300 pM to about 500 pM, about 300 pM to about 450 pM, about 300 pM to about 400 pM, or about 400 pM to about 500 pM. In some embodiments, the antibody has an antigen-binding affinity of at least about 0.001 pM.

[0112] In some embodiments, the IL trap is about 0.1×10 -9 Less than M, approximately 0.2 x 10 -9 Less than M, approximately 0.3 x 10 -9 Less than M, approximately 0.4 x 10 -9 Less than M, approximately 0.5 x 10 -9 Less than M, approximately 0.6 x 10 -9 Less than M, approximately 0.7 x 10 -9 Less than M, approximately 0.8 x 10 -9 Less than M, approximately 0.9 x 10 -9 Less than M, approximately 1 x 10 -9 Less than M, approximately 1.1 x 10 -9 Less than M, approximately 1.2 x 10 -9 Less than M, approximately 1.3 x 10 -9 Less than M, approximately 1.4 x 10 -9Less than M, approximately 1.5 x 10 -9 Less than M, approximately 1.6 x 10 -9 Less than M, approximately 1.7 x 10 -9 Less than M, approximately 1.8 x 10 -9 Less than M, approximately 1.9 x 10 -9 Less than M, approximately 2 x 10 -9 Less than M, approximately 2.1 x 10 -9 Less than M, approximately 2.2 x 10 -9 Less than M, approximately 2.3 x 10 -9 Less than M, approximately 2.4 x 10 -9 Less than M, approximately 2.5 x 10 -9 Less than M, approximately 2.6 x 10 -9 Less than M, approximately 2.7 x 10 -9 Less than M, approximately 2.8 x 10 -9 Less than M, approximately 2.9 x 10 -9 Less than M, approximately 3 x 10 -9 Less than M, approximately 3.1 x 10 -9 Less than M, approximately 3.2 x 10 -9 Less than M, approximately 3.3 x 10 -9 Less than M, approximately 3.4 x 10 -9 Less than M, approximately 3.5 x 10 -9 Less than M, approximately 3.6 x 10 -9 Less than M, approximately 3.7 x 10 -9 Less than M, approximately 3.8 x 10 -9 Less than M, approximately 3.9 x 10 -9 Less than M or about 4 x 10 -9 M, or has an IC50 within a range defined by any two of the above values. For example, in some embodiments, the IL trap has an IL IC50 of less than about 0.1 x 10 -10 M ~ approx. 4×10 -10 M, approx. 0.1×10 -10 M ~ approx. 3.5×10 -10 M, approx. 0.1×10 -10 M ~ approx. 3×10 -10 M, approx. 0.1×10 -10 M ~ approx. 2.5×10 -10 M, approx. 0.1×10 -10 M ~ approx. 2×10 -10 M, approx. 0.1×10 -10 M ~ approx. 1.5×10 -10 M, approx. 0.1×10 -10 M ~ approx. 1×10-10 M, approx. 0.1×10 -10 M ~ approx. 0.5×10 -10 M, approx. 0.5×10 -10 M ~ approx. 4×10 -10 M, approx. 0.5×10 -10 M ~ approx. 3.5×10 -10 M, approx. 0.5×10 -10 M ~ approx. 3×10 -10 M, approx. 0.5×10 -10 M ~ approx. 2.5×10 -10 M, approx. 0.5×10 -10 M ~ approx. 2×10 -10 M, approx. 0.5×10 -10 M ~ approx. 1.5×10 -10 M, approx. 0.5×10 -10 M ~ approx. 1×10 -10 M, about 1 x 10 -10 M ~ approx. 4×10 -10 M, about 1 x 10 -10 M ~ approx. 3.5×10 -10 M, about 1 x 10 -10 M ~ approx. 3×10 -10 M, about 1 x 10 -10 M ~ approx. 2.5×10 -10 M, about 1 x 10 -10 M ~ approx. 2×10 -10 M, approx. 2 x 10 -10 M ~ approx. 4×10 -10 M, approx. 2 x 10 -10 M ~ approx. 3.5×10 -10 M, approx. 2 x 10 -10 M ~ approx. 3×10 -10 M, or approximately 3 x 10 -10 M ~ approx. 4×10 -10 M. In some embodiments, the IL trap has an IL IC50 of 2 nM or less.

[0113] In some embodiments, the IL trap is an IL-1 trap, an IL-1α trap, an IL-1β trap, an IL-1Ra trap, an IL-2 trap, an IL-3 trap, an IL-4 trap, an IL-5 trap, an IL-6 trap, an IL-7 trap, an IL-8 trap, an IL-9 trap, an IL-10 trap, an IL-11 trap, an IL-12 trap, an IL-13 trap the IL-4 trap, IL-5 trap, IL-6 trap, IL-7 trap, IL-8 trap, IL-9 trap, IL-10 trap, IL-11 trap, IL-12 trap, IL-13 trap, IL-14 trap, IL-15 trap, IL-16 trap, IL-17 trap, IL-17A-F trap, IL-18 trap, IL-19 trap, IL-20 trap, IL-21 trap, IL-22 trap, IL-23 trap, IL-24 trap, IL-25 trap, IL-26 trap, IL-27 trap, IL-28 trap, IL-29 trap, IL-30 trap, IL-31 trap, IL-32 trap, IL-33 trap, IL-34 trap, IL-35 trap, IL-36Ra trap, IL-36α trap, IL-36β trap, IL-36γ trap, IL-37 trap, or IL-38 trap.

[0114] In some embodiments, the IL trap comprises a trap for a member of the IL-1 family, e.g., IL-1α, IL-1β, IL-1Ra, IL-18, IL-33, IL-36α, IL-36β, IL-36γ, IL-36Ra, IL-37, or IL-38. In some embodiments, the IL trap comprises accessory proteins of the same receptor for binding to IL-1α, IL-1β, IL-1Ra, IL-33, IL-36α, IL-36β, IL-36γ.

[0115] In some embodiments, the IL trap comprises an IL receptor protein. In some embodiments, the IL trap receptor protein comprises the receptor protein IL-1R1, IL-2Rβ, IL-2Rγ, IL-3Rα, CSF2RB, IL-4R, IL-2Rγ / IL-13Rα1, IL-5Rα, IL-6Rα, gp130, IL-7Rα, IL-9R, IL-11Rα, IL-12Rβ1, IL-12Rβ2, IL-13Rα1, IL-13Rα2, IL-4R, IL-15Rα, CD4, CD9, IL-21R, IL-12Rβ1, IL-23R, IL-27Rα, IL-31Rα, OSMR, CSF-1R, or ST2.

[0116] In some embodiments, IL traps include traps for members of the IL-family, such as IL-6, LIF, CNTF, CLCF1, OSM, IL-11, IL-27, IL-35, IL-39.

[0117] In some embodiments, the IL-trap is a trap for ILs that contain a common cytokine receptor gamma chain (γc), e.g., IL-2, IL-4, IL-7, IL-9, IL-15, IL-21, etc. In some embodiments, the IL-trap is a trap for ILs that contain a common cytokine β receptor chain (βc), e.g., IL-3, IL-5, GM-CSF, etc.

[0118] In some embodiments, the IL accessory protein is IL1RacP. In some embodiments, the IL accessory protein is GP130 (IL6Rb).

[0119] In some embodiments, the antibody or fragment thereof is an anti-HTRA1 antibody or fragment thereof.

[0120] In some embodiments, the trap-antibody fusion or trap-Fab comprises an IL trap that is an IL-1 trap and an antibody or fragment thereof that is an anti-HTRA1 antibody or fragment thereof.

[0121] In some embodiments, the trap-antibody fusion comprises an IL trap that is an IL-1 trap. In some embodiments, the IL-1 trap is an IL1R1 and IL1R acP. In some embodiments, the IL-1 trap has an antibody that has an IL-1 binding affinity of about 0.01 pM to about 100 pM and is an anti-HTRA1 antibody. For example, in some embodiments, the IL-1 trap has an IL-1 binding affinity of about 0.01 pM, about 0.05 pM, about 0.1 pM, about 0.2 pM, about 0.25 pM, about 0.3 pM, about 0.4 pM, about 0.5 pM, about 0.6 pM, about 0.7 pM, about 0.8 pM, about 0.9 pM, about 1 pM, about 5 pM, about 10 pM, about 15 pM, about 20 pM, about 25 pM, about 30 pM, about 40 pM, about 50 pM, about 60 pM, about 70 pM, about 75 pM, about 80 pM, about 90 pM, about 95 pM, or about 100 pM, or an IL-1 binding affinity within a range defined by any two of the above values. For example, in some embodiments, the IL-1 trap has an IL-1 binding affinity between or below the following values: about 0.01 pM to about 100 pM, about 0.01 pM to about 75 pM, about 0.01 pM to about 50 pM, about 0.01 pM to about 25 pM, about 0.01 pM to about 10 pM, about 0.01 pM to about 5 pM, about 0.01 pM to about 1 pM, about 0.01 pM to about 0.1 pM, about 0.1 pM to about 100 pM, about 0.1 pM to about 75 pM, about 0.1 pM to about 50 pM, about 0.1 pM to about 25 pM, about 0.1 pM to about 10 pM, about 0.1 pM to about 1 pM, pM ~ about 100pM, about 1pM - about 75pM, about 1pM - about 50pM, about 1pM - about 25pM, about 1pM - about 10pM, about 1pM - about 5 pM, about 5 pM to about 100 pM, about 5 pM to about 75 pM, about 5 pM to about 50 pM, about 5 pM to about 25 pM, about 5 pM to about 10 pM, about 10 pM ~ about 100pM, about 10pM - about 75pM, about 10pM - about 50pM, about 10pM - about 25pM, about 25pM - about 100pM, about 2 5 pM to about 75 pM, about 25 pM to about 50 pM, about 50 pM to about 100 pM, about 50 pM to about 75 pM, or 75 pM to about 100 pM. In some embodiments, the anti-HTRA1 antibody has an HTRA1 binding affinity of about 50 pM to about 500 pM or less.For example, in some embodiments, the anti-HTRA1 antibody or fragment thereof has a cytotoxicity of about 50 pM or less, about 55 pM or less, about 60 pM or less, about 65 pM or less, about 70 pM or less, about 75 pM or less, about 80 pM or less, about 85 pM or less, about 90 pM or less, about 95 pM or less, about 100 pM or less, about 105 pM or less, about 110 pM or less, about 115 pM or less, about 120 pM or less, about 125 pM or less, about 130 pM or less, about 135 pM or less, about 140 pM or less, about 145 pM or less, about 150 pM or less, about 155 pM or less, about 160 pM or less, about 16 ... pM or less, about 165 pM or less, about 170 pM or less, about 175 pM or less, about 180 pM or less, about 185 pM or less, about 190 pM or less, about 195 pM or less, about 200 pM or less, about 205 pM or less, about 210 pM or less, about 215 pM or less, about 220 pM or less , about 225 pM or less, about 230 pM or less, about 235 pM or less, about 240 pM or less, about 245 pM or less, about 250 pM or less, about 255 pM or less, about 260 pM or less, about 265 pM or less, about 270 pM or less, about 275 pM or less, about 280 pM or less, about 285 pM or less, about 290 pM or less, about 295 pM or less, about 300 pM or less, about 305 pM or less, about 310 pM or less, about 315 pM or less, about 320 pM or less, about 325 pM or less, about 330 pM or less, about 335 pM or less, about 340 pM or less, about 345 pM or less , about 350 pM or less, about 355 pM or less, about 360 pM or less, about 365 pM or less, about 370 pM or less, about 375 pM or less, about 380 pM or less, about 385 pM or less, about 390 pM or less, about 395 pM or less, about 400 pM or less, about 405 pM or less, about 410 pM or less, about 415 pM or less, about 420 pM or less, about 425 pM or less, about 430 pM or less, about 435 pM or less, about 440 pM or less, about 445 pM or less, about 450 pM or less, about 455 pM or less, about 460 pM or less, about 465 pM or less, about 470 pM or less, about 475 pM or less, about 480 pM or less, about 485 pM or less, about 490 pM or less, about 495 pM or less, or about 500 pM or less, or an HTRA1 binding affinity within a range defined by any two of the above values.For example, in some embodiments, the anti-HTRA1 antibody or fragment thereof has an HTRA1 binding affinity between or less than the following values: about 50 pM to about 500 pM, about 50 pM to about 450 pM, about 50 pM to about 400 pM, about 50 pM to about 350 pM, about 50 pM to about 300 pM, about 50 pM to about 250 pM, about 50 pM to about 200 pM, about 50 pM to about 150 pM, about 50 pM to about 100 pM, about 100 pM to about 500 pM, about 100 pM to about 450 pM, or about 100 pM. In some embodiments, the anti-HTRA1 antibody or fragment thereof has an HTRA1 binding affinity of at least about 0.01 pM.

[0122] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an IL-trap that is an IL-1 trap. In some embodiments, the IL-1 trap comprises IL1R1 and IL1RacP. In some embodiments, the IL-1 trap has an IL-1 binding affinity of less than about 1 nM. In some embodiments, the trap-antibody fusion comprises an antibody or fragment thereof that is an anti-HTRA1 antibody or fragment thereof. In some embodiments, the anti-HTRA1 antibody or fragment thereof has an HTRA1 binding affinity of less than about 1 nM.

[0123] In some embodiments, the trap-antibody or trap-Fab fusion comprises an IL-trap that is an IL-33 trap and an antibody or fragment thereof that is an anti-HTRA1 antibody or fragment thereof.

[0124] In some embodiments, the trap-antibody or trap-Fab fusion comprises an IL-trap that is an IL-33 trap and an antibody or fragment thereof that is an anti-HTRA1 antibody, wherein the IL-33 trap comprises ST2 and IL1RacP.

[0125] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an IL-33 trap that is an IL-33 trap and an antibody or fragment thereof that is an anti-HTRA1 antibody or fragment thereof, wherein the IL-33 trap comprises ST2 and IL1RacP; the IL-33 trap has an IL-33 binding affinity of less than about 1 nM; and the anti-HTRA1 antibody or fragment thereof has an HTRA1 binding affinity of less than about 1 nM.

[0126] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an IL-trap that is an IL-33 trap. In some embodiments, the IL-33 trap comprises ST2 and IL1RacP. In some embodiments, the IL-33 trap has an IL-33 binding affinity of about 0.01 pM to about 100 pM. For example, in some embodiments, an IL-33 trap has an IL-33 binding affinity of about 0.01 pM, about 0.05 pM, about 0.1 pM, about 0.2 pM, about 0.25 pM, about 0.3 pM, about 0.4 pM, about 0.5 pM, about 0.6 pM, about 0.7 pM, about 0.8 pM, about 0.9 pM, about 1 pM, about 5 pM, about 10 pM, about 15 pM, about 20 pM, about 25 pM, about 30 pM, about 40 pM, about 50 pM, about 60 pM, about 70 pM, about 75 pM, about 80 pM, about 90 pM, about 95 pM, or about 100 pM, or a binding affinity that is within a range defined by any two of the above values. For example, in some embodiments, the IL-33 trap has an IL-33 binding affinity between or below the following values: about 0.001 pM to about 100 pM, about 0.001 pM to about 75 pM, about 0.001 pM to about 50 pM, about 0.001 pM to about 25 pM, about 0.001 pM to about 10 pM, about 0.001 pM to about 5 pM, about 0.001 pM to about 1 pM, about 0.001 pM to about 0.1 pM, about 0.001 pM to about 0. 05pM, approximately 0.001pM to approximately 0.01pM, approximately 0.01pM to approximately 100pM, approximately 0.01pM to approximately 75pM, approximately 0.01pM to approximately 50pM, approximately 0.01pM to approximately 25pM, approximately 0.01pM to approximately 10pM, approximately 0.01pM to approximately 5pM, approximately 0.01pM to approximately 1pM, approximately 0.01pM to approximately 0.1pM, approximately 0.1pM to approximately 100pM, approximately 0.1pM to approximately 75pM, approximately 0.1pM to approximately 50pM, approximately 0.1pM to approximately 25pM, approximately 0.1pM to about 10pM, about 0.1pM to about 1pM, about 1pM to about 100pM, about 1pM to about 75pM, about 1pM to about 50pM, about 1pM to about 25pM , about 1 pM to about 10 pM, about 1 pM to about 5 pM, about 5 pM to about 100 pM, about 5 pM to about 75 pM, about 5 pM to about 50 pM, about 5 pM to about 25 pM, about 5 pM to about 10 pM, about 10 pM to about 100 pM, about 10 pM to about 75 pM, about 10 pM to about 50 pM, about 10 pM to about 25 pM, about 25 pM to about 100 pM, about 25 pM to about 75 pM, about 25 pM to about 50 pM, about 50 pM to about 100 pM, about 50 pM to about 75 pM, or 75 pM to about 100 pM. In some embodiments, the IL-33 trap has an IL-33 binding affinity of at least about 0.01 pM. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an antibody or fragment thereof that is an anti-HTRA1 antibody. In some embodiments, the anti-HTRA1 antibody has an HTRA1 binding affinity of about 5 pM to about 500 pM or less.For example, in some embodiments, the anti-HTRA1 antibody or fragment thereof has a cytotoxicity of about 50 pM or less, about 55 pM or less, about 60 pM or less, about 65 pM or less, about 70 pM or less, about 75 pM or less, about 80 pM or less, about 85 pM or less, about 90 pM or less, about 95 pM or less, about 100 pM or less, about 105 pM or less, about 110 pM or less, about 115 pM or less, about 120 pM or less, about 125 pM or less, about 130 pM or less, about 135 pM or less, about 140 pM or less, about 145 pM or less, about 150 pM or less, about 155 pM or less, about 160 pM or less, about 165 pM or less, about 170 pM or less, about 175 pM or less, about 180 pM or less, about 185 pM or less, about 190 pM or less, about 195 pM or less, about 200 pM or less, about 205 pM or less, about 210 pM or less, about 215 pM or less, about 220 pM or less, about 225 pM or less, about 230 pM or less, about 235 pM or less, about 240 pM or less, about 245 pM or less, about 250 pM or less, about 255 pM or less, about 260 pM or less, about 265 pM or less, about 270 pM or less, about 275 pM or less, about 280 pM or less, about 285 pM or less, about 290 pM or less, about 300 p 60pM or less, about 165pM or less, about 170pM or less, about 175pM or less, about 180pM or less, about 185pM or less, about 190pM or less, about 195pM or less, about 200pM or less, about 205pM or less, about 210pM or less, about 215pM or less, about 220pM Below, about 225 pM or less, about 230 pM or less, about 235 pM or less, about 240 pM or less, about 245 pM or less, about 250 pM or less, about 255 pM or less, about 260 pM or less, about 265 pM or less, about 270 pM or less, about 275 pM or less, about 280 pM or less, about 285pM or less, about 290pM or less, about 295pM or less, about 300pM or less, about 305pM or less, about 310pM or less, about 315pM or less, about 320pM or less, about 325pM or less, about 330pM or less, about 335pM or less, about 340pM or less, about 345p M or less, about 350 pM or less, about 355 pM or less, about 360 pM or less, about 365 pM or less, about 370 pM or less, about 375 pM or less, about 380 pM or less, about 385 pM or less, about 390 pM or less, about 395 pM or less, about 400 pM or less, about 405 pM or less, has an HTRA1 binding affinity of about 410 pM or less, about 415 pM or less, about 420 pM or less, about 425 pM or less, about 430 pM or less, about 435 pM or less, about 440 pM or less, about 445 pM or less, about 450 pM or less, about 455 pM or less, about 460 pM or less, about 465 pM or less, about 470 pM or less, about 475 pM or less, about 480 pM or less, about 485 pM or less, about 490 pM or less, about 495 pM or less, or about 500 pM or less, or a binding affinity within a range defined by any two of the above values.For example, in some embodiments, the anti-HTRA1 antibody has an HTRA1 binding affinity between or below the following values: about 50 pM to about 500 pM, about 50 pM to about 450 pM, about 50 pM to about 400 pM, about 50 pM to about 350 pM, about 50 pM to about 300 pM, about 50 pM to about 250 pM, about 50 pM to about 200 pM, about 50 pM to about 150 pM, about 50 pM to about 100 pM, about 100 pM to about 500 pM, about 100 pM to about 450 pM , about 100 pM to about 400 pM, about 100 pM to about 350 pM, about 100 pM to about 300 pM, about 100 pM to about 250 pM, about 100 pM to about 200 pM, about 200 pM to about 500 pM, about 200 pM to about 450 pM, about 200 pM to about 400 pM, about 200 pM to about 350 pM, about 200 pM to about 300 pM, about 300 pM to about 500 pM, about 300 pM to about 450 pM, about 300 pM to about 400 pM, or about 400 pM to about 500 pM. In some embodiments, the anti-HTRA1 antibody or fragment thereof has an HTRA1 binding affinity of at least about 0.01 pM.

[0127] In some embodiments, the trap-antibody or trap-Fab fusion comprises an IL-trap that is an IL-6 trap and an antibody or fragment thereof that is an anti-HTRA1 antibody.

[0128] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an IL-trap that is an IL-6 trap. In some embodiments, the IL-6 trap comprises gp130 (IL6Rβ) and IL-6Rα. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an antibody or fragment thereof that is an anti-HTRA1 antibody.

[0129] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an IL-trap that is an IL-6 trap. In some embodiments, the IL-6 trap comprises gp130 (IL6Rβ) and IL-6Rα. In some embodiments, the IL-6 trap has an IL-6 binding affinity of less than about 1 nM. In some embodiments, the trap-antibody fusion comprises an antibody that is an anti-HTRA1 antibody. In some embodiments, the anti-HTRA1 antibody or fragment thereof has an HTRA1 binding affinity of less than about 1 nM.

[0130] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an IL-6 trap. In some embodiments, the IL-6 trap comprises gp130 (IL6Rβ) and IL-6Rα. In some embodiments, the IL-6 trap has an IL-6 binding affinity of about 0.01 pM to about 100 pM. For example, in some embodiments, the IL-6 trap has an IL-6 binding affinity of about 0.01 pM, about 0.05 pM, about 0.1 pM, about 0.2 pM, about 0.25 pM, about 0.3 pM, about 0.4 pM, about 0.5 pM, about 0.6 pM, about 0.7 pM, about 0.8 pM, about 0.9 pM, about 1 pM, about 5 pM, about 10 pM, about 15 pM, about 20 pM, about 25 pM, about 30 pM, about 40 pM, about 50 pM, about 60 pM, about 70 pM, about 75 pM, about 80 pM, about 90 pM, about 95 pM, or about 100 pM, or a binding affinity that is within a range defined by any two of the above values.For example, in some embodiments, the IL-33 trap may be present at a concentration of about 0.001 pM to about 100 pM, about 0.001 pM to about 75 pM, about 0.001 pM to about 50 pM, about 0.001 pM to about 25 pM, about 0.001 pM to about 10 pM, about 0.001 pM to about 5 pM, about 0.001 pM to about 1 pM, about 0.001 pM to about 0.1 pM, or about 0.001 pM to about 0 .05pM, about 0.001pM to about 0.01pM, about 0.01pM to about 100pM, about 0.01pM to about 75pM, about 0.01pM to about 50pM, about 0.01pM to about 25pM , about 0.01pM to about 10pM, about 0.01pM to about 5pM, about 0.01pM to about 1pM, about 0.01pM to about 0.1pM, about 0.1pM to about 100pM, about 0.1pM to about 75 pM, about 0.1 pM to about 50 pM, about 0.1 pM to about 25 pM, about 0.1 pM to about 10 pM, about 0.1 pM to about 1 pM, about 1 pM to about 100 pM, about 1 pM to about 75 pM, about 1 pM~about 50pM, about 1pM~about 25pM, about 1pM~about 10pM, about 1pM~about 5pM, about 5pM~about 100pM, about 5pM~about 75pM, about 5pM~about 50pM, about 5pM The IL-6 trap has an IL-33 binding affinity of about 25 pM to about 25 pM, about 5 pM to about 10 pM, about 10 pM to about 100 pM, about 10 pM to about 75 pM, about 10 pM to about 50 pM, about 10 pM to about 25 pM, about 25 pM to about 100 pM, about 25 pM to about 75 pM, about 25 pM to about 50 pM, about 50 pM to about 100 pM, about 50 pM to about 75 pM, or 75 pM to about 100 pM. In some embodiments, the IL-6 trap has an IL-6 binding affinity of at least about 0.01 pM. In some embodiments, the trap-antibody fusion comprises an antibody or fragment thereof that is an anti-HTRA1 antibody. In some embodiments, the anti-HTRA1 antibody or fragment thereof has an HTRA1 binding affinity of about 5 pM to about 500 pM.For example, in some embodiments, the anti-HTRA1 antibody or fragment thereof has a cytotoxicity of about 50 pM, about 55 pM, about 60 pM, about 65 pM, about 70 pM, about 75 pM, about 80 pM, about 85 pM, about 90 pM, about 95 pM, about 100 pM, about 105 pM, about 110 pM, about 115 pM, about 120 pM, about 125 pM, about 130 pM, about 135 pM, about 140 pM, about 145 pM, about 150 pM, about 155 pM, about 160 pM, about 165 pM, about 170 pM, about 175 pM, about 180 pM, about 185 pM, about 190 pM, or about. 195pM, approx. 200pM, approx. 205pM, approx. 210pM, approx. 215pM, approx. 220pM, approx. 225pM, approx. 230pM, approx. 235p M, about 240pM, about 245pM, about 250pM, about 255pM, about 260pM, about 265pM, about 270pM, about 275pM, about 28 0pM, approx. 285pM, approx. 290pM, approx. 295pM, approx. 300pM, approx. 305pM, approx. 310pM, approx. 315pM, approx. 320pM, approx. 325pM, about 330pM, about 335pM, about 340pM, about 345pM, about 350pM, about 355pM, about 360pM, about 365pM , about 370 pM, about 375 pM, about 380 pM, about 385 pM, about 390 pM, about 395 pM, about 400 pM, about 405 pM, about 410 pM, about 415 pM, about 420 pM, about 425 pM, about 430 pM, about 435 pM, about 440 pM, about 445 pM, about 450 pM, about 455 pM, about 460 pM, about 465 pM, about 470 pM, about 475 pM, about 480 pM, about 485 pM, about 490 pM, about 495 pM, or about 500 pM, or a binding affinity within a range defined by any two of the above values. For example, in some embodiments, the anti-HTRA1 antibody has a concentration of about 50 pM to about 500 pM, about 50 pM to about 450 pM, about 50 pM to about 400 pM, about 50 pM to about 350 pM, about 50 pM to about 300 pM, about 50 pM to about 250 pM, about 50 pM to about 200 pM, about 50 pM to about 150 pM, about 50 pM to about 100 pM, about 100 pM to about 500 pM, about 100 pM to about 450 pM, about 100 pM to about 400 pM, about 100 pM to about 500 pM It has an HTRA1 binding affinity of about 350 pM, about 100 pM to about 300 pM, about 100 pM to about 250 pM, about 100 pM to about 200 pM, about 200 pM to about 500 pM, about 200 pM to about 450 pM, about 200 pM to about 400 pM, about 200 pM to about 350 pM, about 200 pM to about 300 pM, about 300 pM to about 500 pM, about 300 pM to about 450 pM, about 300 pM to about 400 pM, or about 400 pM to about 500 pM.

[0131] FIG. 17 shows representative embodiments of the full length and individual regions of the IL-1, IL-6, IL-33, and VEGF receptor sequences.

[0132] In some embodiments, the trap-antibody or trap-Fab fusion comprises an IL trap that includes a receptor sequence that is the receptor sequence in FIG.

[0133] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an IL trap comprising a receptor sequence that is the receptor sequence in any one of SEQ ID NOs: 1-15 or 67-71. In some embodiments, the trap-antibody fusion comprises a receptor sequence that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to the receptor sequence in any one of SEQ ID NOs: 1-15 or 67-71. In some embodiments, the trap-antibody fusion comprises a receptor sequence that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to the receptor sequence in any one of SEQ ID NOs: 1-15 or 67-71.

[0134] Table 1 lists several embodiments of the full length and each region of the IL-1 receptor sequence, the IL-6 receptor sequence, the IL-33 receptor sequence, the VEGF receptor sequence, and the TNFα receptor sequence.

[0135] [Table 1-1]

[0136] Table 1 continued [Table 1-2]

[0137] Table 1 continued [Table 1-3]

[0138] Table 1 continued [Table 1-4]

[0139] Table 1 continued [Table 1-5]

[0140] Where applicable, selected amino acid regions within the receptor are shown in brackets.

[0141] In some embodiments, the trap-antibody or trap-Fab fusion comprises an IL trap that comprises a receptor sequence that is a receptor sequence in Table 1.

[0142] FIG. 18 shows some representative embodiments of IgG constant and variable region sequences.

[0143] In some embodiments, the trap-antibody or trap-Fab fusion comprises IgG constant and variable region sequences that are the IgG constant and variable region sequences in FIG.

[0144] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an antibody having a variable domain sequence that is the variable domain sequence in any one of SEQ ID NOs: 30-44. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an antibody having a variable domain sequence that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to the variable domain sequence in any one of SEQ ID NOs: 30-44. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an antibody having a variable domain sequence that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to the variable domain sequence in any one of SEQ ID NOs: 30-44.

[0145] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an antibody having a constant domain sequence that is the constant domain sequence in any one of SEQ ID NOs: 28-29, 45-47, or 64-66. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an antibody having a constant domain sequence that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to the constant domain sequence in any one of SEQ ID NOs: 28-29, 45-47, or 64-66. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an antibody having a constant domain sequence that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to the constant domain sequence in any one of SEQ ID NOs: 28-29, 45-47, or 64-66.

[0146] Table 2 lists some embodiments of IgG constant and variable region sequences.

[0147] [Table 2-1]

[0148] Table 2 continued [Table 2-2]

[0149] Table 2 continued [Table 2-3]

[0150] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an antibody having a variable domain sequence that is a variable domain sequence in Table 2.

[0151] FIG. 19 shows some representative embodiments of linkers suitable for use in connecting an IL receptor protein with an antibody variable domain.

[0152] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a linker that is the linker in FIG.

[0153] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises an IL receptor protein linked to an antibody variable domain. The trap-antibody fusion comprises a linker comprising one or more repeats. In some embodiments, the one or more repeats comprise repeats of GGGGS (SEQ ID NO: 24). In some embodiments, the trap-antibody fusion comprises one, two, three, four, five, six, seven, or eight repeats including a linker. In some embodiments, the trap-antibody fusion comprises one, two, three, four, five, six, seven, or eight GGGGS (SEQ ID NO: 24) repeats including a linker. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a linker that is the linker in any one of SEQ ID NOs: 24-27. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a linker that is the linker in any one of SEQ ID NOs: 24 (GGGGS). In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a linker that is the linker in any one of SEQ ID NOs: 25 (GGGGSGGGGS). In some embodiments, the trap-antibody fusion comprises a linker that is the linker in any one of SEQ ID NOs: 26 (GGGGSGGGGSGGGGS). In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a linker that is the linker in any one of SEQ ID NOs: 27 (GGGGSGGGGSGGGGS). In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a linker that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to the linker in any one of SEQ ID NOs: 24-27. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a linker that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to the linker in any one of SEQ ID NOs: 24-27.

[0154] Table 3 shows some embodiments of linkers suitable for use in connecting an IL receptor protein with an antibody variable domain.

[0155] [Table 3]

[0156] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a linker that is a linker in Table 3. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a linker that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to a linker in Table 3. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a linker that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to a linker in Table 3.

[0157] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a linker of up to 20 amino acids. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a linker of 1 amino acid, 2 amino acids, 3 amino acids, 4 amino acids, 5 amino acids, The linker may be 1-20 amino acids, 6 amino acids, 7 amino acids, 8 amino acids, 9 amino acids, 10 amino acids, 11 amino acids, 12 amino acids, 13 amino acids, 14 amino acids, 15 amino acids, 16 amino acids, 17 amino acids, 18 amino acids, 19 amino acids, or 20 amino acids, or a number of amino acids within a range defined by any two of the above values. For example, in some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a linker that is 1-20 amino acids, 1-15 amino acids, 1-10 amino acids, 1-7 amino acids, 1-5 amino acids, 1-3 amino acids, 3-20 amino acids, 3-15 amino acids, 3-10 amino acids, 3-7 amino acids, 3-5 amino acids, 5-20 amino acids, 5-15 amino acids, 5-10 amino acids, 5-7 amino acids, 7-20 amino acids, 7-15 amino acids, 7-10 amino acids, 10-20 amino acids, 10-15 amino acids, or 15-20 amino acids in length.

[0158] FIG. 20 shows some representative embodiments of signal peptide sequences suitable for use in the trap-antibody or trap-Fab fusions disclosed herein.

[0159] In some embodiments, the trap-antibody fusion or trap-Fab comprises a signal peptide, which is the signal peptide in FIG.

[0160] FIG. 4 shows several embodiments of signal peptide sequences suitable for use in the trap-antibody or trap-Fab fusions disclosed herein.

[0161] [Table 4]

[0162] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a signal peptide that is a signal peptide in Table 4. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to a signal peptide in Table 4. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to a signal peptide in Table 4.

[0163] In some embodiments, trap-antibody fusions or trap-Fab fusions are generated by fusing the extracellular domains of the heterodimeric human IL-1 receptors IL1RAcP, IL1R1, and IL1R2 to an anti-human IL-6 antibody. In some embodiments, each receptor is fused N-terminally to the VH or VL domain. The HC / LC heterodimer places the IL-1 receptors in close proximity to mimic the native IL-1 binding mechanism. In some embodiments, IL1RAcP is linked in tandem with ILR1 or ILR2 and then fused to the heavy and / or light chains of an anti-IL-6 antibody. This fusion protein is then combined with various signal peptides to drive extracellular secretion in mammalian cells.

[0164] 4 is a schematic diagram showing various embodiments of IL-1 Trap and IgG fusion configurations. The dark crescent represents IL1R1 or IL1R2. The light crescent represents IL1RAcP. In some embodiments, IL1RAcP and IL1R1 or IL1R2 are linked in tandem to both the heavy or light chain arms of the antibody. In some embodiments, IL1RAcP and IL1R1 or IL1R2 are linked in tandem to both the heavy and light chain arms of the antibody. In some embodiments, IL1R1 or IL1R2 and IL1RAcP are each linked to the heavy and light chains of both antibody arms, respectively. In some embodiments, IL1RAcP and IL1R1 or IL1R2 are each linked to the heavy and light chains of both antibody arms, respectively.

[0165] Table 5 lists several embodiments of sequence compositions of IL-1 trap anti-IL-6 antibodies, IL-6 traps, IL-33 traps, IL-1 trap anti-IL-6 Fabs, and bivalent VEGF trap anti-IL-6 Fabs. As listed in Table 5, the sequence compositions represent sequence numbers (SEQ IDs) that can be covalently linked to each other, from left to right, for heavy chain formation and light chain formation.

[0166] [Table 5-1]

[0167] Table 5 continued [Table 5-2]

[0168] Table 5 continued [Table 5-3]

[0169] Table 5 continued [Table 5-4]

[0170] Table 5 continued [Table 5-5]

[0171] In some embodiments, the trap-antibody fusion or trap-Fab fusion is a trap-antibody fusion in Table 5. In some embodiments, the trap-antibody fusion is a trap-antibody fusion that has about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to a trap-antibody fusion in Table 5.

[0172] In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a combination of SEQ ID NOs (SEQ IDs) disclosed herein. In some embodiments, the trap-antibody fusion comprises a combination of SEQ ID NOs (SEQ IDs) disclosed in Table 5. In some embodiments, the trap-antibody fusion or trap-Fab is a trap-antibody fusion that has about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to a trap-antibody fusion comprising a combination of SEQ ID NOs (SEQ IDs) disclosed in Table 5. In some embodiments, the trap-antibody fusion or trap-Fab fusion comprises a heavy chain that has about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to a trap-antibody fusion or trap-Fab fusion comprising a combination of SEQ ID NOs (SEQ IDs) disclosed in Table 5.

[0173] In some embodiments, any one of the configurations in Table 5 may be used to treat one or more disorders. In some embodiments, the disorders include diabetic retinopathy, early, intermediate, or advanced age-related macular degeneration (AMD), retinopathy of prematurity (ROP), dry AMD, geographic atrophy, wet (neovascular, wet) AMD, polypoidal choroidal vasculopathy, ocular inflammation, HTRA1-related disorders, and / or IL-1-related disorders, scleritis, diabetic macular edema, diabetic retinopathy, wet age-related macular degeneration, uveitis, non-infectious uveitis, macular edema associated with uveitis, cytokine release syndrome after CAR-T or similar immuno-oncology therapy, and / or suppression of induction of IL-6 expression observed after treatment with anti-PD-1 / PD-L1 molecules, cancer, cerebral edema in glioblastoma, IL-6-related disorders, and / or VEGF-related disorders. In some embodiments, the disorder is inflammation of the eye. In some embodiments, the disorder is ocular inflammation. In some embodiments, any one of the compositions in Table 5 can be used to treat one or more of the disorders in Figure 25.

[0174] Figure 21 shows some representative embodiments of full-length heavy chain sequences suitable for use in the trap-antibody fusions disclosed herein. In some embodiments, the trap-antibody fusion comprises the heavy chain in Figure 21. In some embodiments, the trap-antibody fusion comprises a heavy chain that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to the heavy chain in Figure 21. In some embodiments, the trap-antibody fusion comprises a heavy chain that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to the heavy chain in Figure 21.

[0175] Figure 22 shows some representative embodiments of full-length light chain sequences suitable for use in the trap-antibody fusions or trap-Fab fusions disclosed herein. In some embodiments, the trap-antibody fusion comprises the light chain in Figure 22. In some embodiments, the trap-antibody fusion comprises a light chain that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to the light chain in Figure 22. In some embodiments, the trap-antibody fusion comprises a light chain that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to the light chain in Figure 22.

[0176] In some embodiments, the trap-antibody fusion comprises an IL-1 trap-anti-HTRA1. In some embodiments, the trap-antibody comprises an IL-33 trap-anti-HTRA1. In some embodiments, the trap-antibody comprises an IL-6 trap-anti-HTRA1.

[0177] Table 6 shows some embodiments of full-length heavy chain sequences of trap-antibodies.

[0178] [Table 6-1]

[0179] Table 6 continued [Table 6-2]

[0180] Table 6 continued [Table 6-3]

[0181] The signal peptide is in bold. The IL trap sequence is in italics. The linker sequence is underlined.

[0182] In some embodiments, the trap-antibody fusion comprises a heavy chain in Table 6. In some embodiments, the trap-antibody fusion comprises a heavy chain that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to a heavy chain in Table 6. In some embodiments, the trap-antibody fusion comprises a heavy chain that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to a heavy chain in Table 6.

[0183] Table 7 shows some embodiments of full-length light chain sequences for trap-antibody fusions.

[0184] [Table 7-1]

[0185] Table 7 continued [Table 7-2]

[0186] Table 7 continued [Table 7-3]

[0187] The signal peptide is in bold. The IL trap sequence is in italics. The linker sequence is underlined.

[0188] In some embodiments, the trap-antibody fusion comprises a light chain in Table 7. In some embodiments, the trap-antibody fusion comprises a signal peptide with about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to a light chain in Table 7. In some embodiments, the trap-antibody fusion comprises a light chain with about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to a heavy chain in Table 7.

[0189] FIG. 23 shows several representative embodiments of full-length heavy chain sequences suitable for use in the trap-Fab fusions disclosed herein.

[0190] In some embodiments, the trap-Fab fusion comprises a heavy chain in Figure 23. In some embodiments, the trap-Fab fusion comprises a heavy chain that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to the heavy chain in Figure 23. In some embodiments, the trap-Fab fusion comprises a heavy chain that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to the heavy chain in Figure 23.

[0191] FIG. 24 shows several representative embodiments of full-length light chain sequences suitable for use in the trap-Fab fusions disclosed herein.

[0192] In some embodiments, the trap-Fab fusion comprises a light chain in Figure 24. In some embodiments, the trap-Fab fusion comprises a light chain that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to the light chain in Figure 24. In some embodiments, the trap-Fab fusion comprises a light chain that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to the light chain in Figure 24.

[0193] Table 8 shows some embodiments of full-length heavy chain sequences for trap-Fab fusions.

[0194] [Table 8]

[0195] The signal peptide is in bold. The IL trap sequence is in italics. The linker sequence is underlined.

[0196] In some embodiments, the trap-Fab fusion comprises a heavy chain in Table 8. In some embodiments, the trap-Fab fusion comprises a heavy chain that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to a heavy chain in Table 8. In some embodiments, the trap-Fab fusion comprises a heavy chain that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to a heavy chain in Table 8.

[0197] Table 9 shows some embodiments of the full-length light chain sequence of the trap-antibody fusion.

[0198] [Table 9]

[0199] The signal peptide is in bold. The IL trap sequence is in italics. The linker sequence is underlined.

[0200] In some embodiments, the trap-Fab fusion comprises a light chain in Table 9. In some embodiments, the trap-Fab fusion comprises a light chain that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to a light chain in Table 9. In some embodiments, the trap-Fab fusion comprises a light chain that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to a heavy light in Table 9.

[0201] In some embodiments, a conjugate shown in Figure 10, Figure 11, or Figure 12 may be used with an array such as that shown in Figure 21 or Figure 22. In some embodiments, a conjugate shown in Figure 13, Figure 14, or Figure 15 may be used with an array such as that shown in Figure 23 or Figure 24.

[0202] In some embodiments, the trap-antibody fusion is an IL-1 trap anti-HTRA1 antibody biopolymer conjugate. The term "anti-HTRA1" refers to a polymer linked to a protein of interest. This term can also be described as a "conjugated" form of the protein. In some embodiments, the IL-1 trap anti-HTRA1 antibody biopolymer conjugate is TA105-OG1802. In some embodiments, the trap-antibody fusion comprises a heavy chain sequence that is SEQ ID NO: 51. In some embodiments, the trap-antibody fusion comprises a heavy chain sequence that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 51. In some embodiments, the trap-antibody fusion comprises a heavy chain sequence that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 51. In some embodiments, the IL-1 trap anti-HTRA1 antibody biopolymer conjugate comprises a light chain sequence that is SEQ ID NO: 57. In some embodiments, the trap-antibody fusion comprises a light chain sequence that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 57. In some embodiments, the trap-antibody fusion comprises a light chain sequence that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 57. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 17, a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 38, and a CH that is SEQ ID NO: 28.In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 17, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 1, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 38, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 28. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 17, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 1, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 38, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 28. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 18, a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 44, and a CL that is SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 18; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 2; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 44; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 18, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 2, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, and about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 44. and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29. In some embodiments, the IL-1 trap anti-HTRA1 fusions may be used to treat or in combination with treatments for diabetic retinopathy, early, intermediate, or advanced age-related macular degeneration (AMD), retinopathy of prematurity (ROP), dry AMD, geographic atrophy, wet (neovascular, wet) AMD, polypoidal choroidal vasculopathy, ocular inflammation, HTRA1-associated disorders, and / or IL-1-associated disorders.

[0203] In some embodiments, the trap-Fab fusion is an IL-1 trap anti-IL-6 Fab biopolymer conjugate. In some embodiments, the trap-Fab fusion is TF2-OG1802. In some embodiments, the trap-Fab fusion comprises a heavy chain sequence that is SEQ ID NO: 60. In some embodiments, the trap-Fab fusion comprises a heavy chain sequence that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 60. In some embodiments, the trap-Fab fusion comprises a heavy chain sequence that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 60. In some embodiments, the trap-Fab fusion comprises a light chain sequence that is SEQ ID NO: 62. In some embodiments, the trap-Fab fusion comprises a light chain sequence that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to SEQ ID NO: 62. In some embodiments, the trap-Fab fusion comprises a light chain sequence that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 62. In some embodiments, the heavy chain of the trap-Fab fusion comprises a signal peptide that is SEQ ID NO: 17, a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 46.In some embodiments, the heavy chain of the trap-Fab fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 17, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 1, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 46. In some embodiments, the heavy chain of the trap-Fab fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 17, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 1, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 46. In some embodiments, the light chain of the trap-Fab fusion comprises a signal peptide that is SEQ ID NO: 18, a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-Fab fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 18, a trap that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 2, a linker that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 25, a VL that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 39, and a CL that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 29. %, about 80%, about 90%, about 95%, or 100% homology to a CL. In some embodiments, the light chain of the trap-Fab fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 18; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 2; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0204] In some embodiments, the trap-antibody fusion comprises an IL-1 trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 17, a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 17, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 1, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 17, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 1, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 18, a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 66.In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 18, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 2, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 18, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 2, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 66. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16. % homology to SEQ ID NO: 39, a VL that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to SEQ ID NO: 39, and a CL that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VL that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 39, and a CL that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 29.

[0205] In some embodiments, the trap-antibody fusion comprises an IL-1 trap and an IL-6 trap. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 18, a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 18, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 2, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 18, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 2, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:17, a trap that is SEQ ID NO:1, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:66.In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 17, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 1, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 17, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 1, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 66. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion is about 70%, about 75%, about 80%, about 90%, about 95%, or 10% of SEQ ID NO: 16. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0206] In some embodiments, the trap-antibody fusion comprises an IL-1 trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 17, a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 17, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 1, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 17, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 1, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 18, a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 18; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 2; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 18; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 2; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0207] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion is SEQ ID NO: 72. It comprises a signal peptide, a trap of SEQ ID NO: 67, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 67, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:67, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 67; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:67; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0208] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 67, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72, about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:67, In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0209] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 67, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 67; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:67; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0210] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 28. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 28. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 28. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 67, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 67; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:67; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0211] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 67, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:67; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30; In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 66. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 67, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 67; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:67; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0212] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 67, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:72, about 70%, about 75%, about 80%, about 95%, or 100% homology to SEQ ID NO:67, a trap having 90%, about 95%, or 100% homology to SEQ ID NO:25; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25; a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:30; and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:67, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:66. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 67; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 17, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 1, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0213] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 68, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:68; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30; In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:68; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:68; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0214] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 28. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 28. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 28. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 68, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:68; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:29.In some embodiments, the light chain of the trap-antibody fusion has a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 72; a trap that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 68; a linker that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 25; a VL that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 39; Contains CL with 100% identity.

[0215] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 68, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 66. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 68, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:68; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:68; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0216] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 68, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 68, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:68, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:66. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:68; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:68; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0217] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:73, a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:69; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25; a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:30; In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 73, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 69, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:73, a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 69; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 69; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0218] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 69, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:69, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 69, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises about 70%, about 75%, about 80%, about 90%, about 95%, or about 100% of SEQ ID NO: 72. comprises a signal peptide with 100% homology, a trap with about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:69, a linker with about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25, a VL with about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:39, and a CL with about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:69; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0219] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:73, a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 69; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30; and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 69; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25; a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30; and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:16, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0220] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 69, a linker that is SEQ ID NO: 25, and a sequence and a CH that is SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 72, a trap that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 69, a linker that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 25, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:69, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VL that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 39, and a CL that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0221] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 69, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:69; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:69; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0222] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 28. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 28. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 28. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 73, a trap that is SEQ ID NO: 69, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 69; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 69; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0223] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 69, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 72, and a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 69. a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25; a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:30; and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:69, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 66.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 69; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:69; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0224] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 69, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:69, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:69, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:66.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 69; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:69; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0225] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 73, a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 73, and a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 70. a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25; a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:30; and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:73, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:70, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:73, a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0226] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 70, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:70, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:64. In this embodiment, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0227] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:73, a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30; and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:73, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:70, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:16, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0228] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 70, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:70, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:16, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0229] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 73, a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29 ... about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to SEQ ID NO: 73. a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0230] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0231] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 28. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 28. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 28. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 73, a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0232] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 70, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 70, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 66. The heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 66. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0233] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25; and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:70, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:66. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:70; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0234] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:73, a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30; and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25; a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30; and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 73, a trap that is SEQ ID NO: 71, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, , and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to SEQ ID NO: 73, a trap that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to SEQ ID NO: 71, a linker that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to SEQ ID NO: 25, a VL that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to SEQ ID NO: 39, and a CL that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0235] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 71, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:71, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 71, and a light chain having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25. 39; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0236] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:73, a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30; and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25; a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30; and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:16, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0237] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 71, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% SEQ ID NO: 72. a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 71, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0238] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 71, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0239] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 64. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 64. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 73, a trap that is SEQ ID NO: 71, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0240] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 28. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 28. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 28. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 73, a trap that is SEQ ID NO: 71, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29 ... about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to SEQ ID NO: 73. a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 73; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0241] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 71, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 71, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:16, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:66.In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 66. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 71, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 72. a peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0242] In some embodiments, the trap-antibody fusion comprises a TNFα trap and an IL-6 antibody. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 65. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 71, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 66. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 71, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 66.In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72, a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:71, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:66. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 71, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that has about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 72. a peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO:29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:72; a trap having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:71; a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:25; a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:39; and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO:29.

[0243] In some embodiments, an anti-TFFα VHH anti-IL-6 antibody fusion is disclosed, in which the fusion heavy chain comprises a signal peptide that is SEQ ID NO: 16, a VHH that is SEQ ID NO: 74, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 28. In some embodiments, the trap fusion heavy chain comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 16, a VHH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 74, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 28. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VHH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 74, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 28. In some embodiments, the fusion light chain comprises a signal peptide that is SEQ ID NO: 16, a VHH that is SEQ ID NO: 74, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 16, a VHH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 74, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VHH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 74, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39, and about 70%, about 75%, or 100% identity to SEQ ID NO: 29. The CL has about 80%, about 90%, about 95%, or 100% identity.

[0244] In some embodiments, an anti-TFFα VHH anti-IL-6 antibody fusion is disclosed, in which the fusion heavy chain comprises a signal peptide that is SEQ ID NO: 16, a VHH that is SEQ ID NO: 74, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 28. In some embodiments, the trap fusion heavy chain comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 16, a VHH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 74, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 28. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VHH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 74, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 28. In some embodiments, the fusion light chain comprises a signal peptide that is SEQ ID NO: 16, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VL that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 39, and a CL that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 29.In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0245] In some embodiments, anti-TFFα VHH anti-IL-6 antibody fusions are disclosed. In some embodiments, the fusion heavy chain comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 28. In some embodiments, the trap fusion heavy chain comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 16, a VH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 30, and a CH that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identical to SEQ ID NO: 28. In some embodiments, the heavy chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 30, and a CH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 28. In some embodiments, the fusion light chain comprises a signal peptide that is SEQ ID NO: 16, a VHH that is SEQ ID NO: 58, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide that is about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homologous to SEQ ID NO: 16, a VHH that is SEQ ID NO: 58, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29. The VHH has 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology; a linker has about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 25; a VL has about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 39; and a CL has about 70%, about 75%, about 80%, about 90%, about 95%, or 100% homology to SEQ ID NO: 29. In some embodiments, the light chain of the trap-antibody fusion comprises a signal peptide having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 16, a VHH having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 58, a linker having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 25, a VL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 39, and a CL having about 70%, about 75%, about 80%, about 90%, about 95%, or 100% identity to SEQ ID NO: 29.

[0246] Some embodiments herein are directed to nucleic acids encoding any of the trap-antibody fusions or trap-Fab fusions disclosed herein. For example, in some embodiments, the nucleic acids encode any of the trap-antibody fusions or trap-Fab fusions in Table 5. Some embodiments herein are directed to vectors comprising nucleic acids encoding any of the trap-antibody fusions or trap-Fab fusions disclosed herein. For example, in some embodiments, the vectors comprise nucleic acids encoding any of the trap-antibody fusions or trap-Fab fusions in Table 5. Some embodiments herein are directed to cells comprising vectors encoding any of the trap-antibody fusions or trap-Fab fusions disclosed herein. For example, in some embodiments, the cells comprise vectors encoding any of the trap-antibody fusions or trap-Fab fusions in Table 5.

[0247] In some embodiments, the receptor protein and antibody are configured as shown in FIG.

[0248] In some embodiments, binding of an IL trap to an IL reduces the activity of the IL. In some embodiments, binding of an antibody to an antigen inhibits the activity of the antigen. In some embodiments, simultaneous binding of an IL trap to an IL and binding of an antibody to an antigen inhibits the activity of the IL and the antigen.

[0249] In some embodiments, binding of the IL trap to the IL reduces the activity of the IL by about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 20%, about 25%, about 30%, about 40%, about 50%, about 60%, about 75%, about 80%, about 90%, about 95%, about 99%, about 100%, about 200%, about 250%, about 300%, about 400%, about 500%, about 600%, about 700%, about 750%, about 800%, about 900%, or 1000%, or a range defined by any two of the above values. For example, in some embodiments, binding of the IL trap to the IL increases the activity of the IL by about 1% to about 1000%, about 1% to about 750%, about 1% to about 500%, about 1% to about 250%, about 1% to about 150%, about 1% to about 100%, about 1% to about 75%, about 1% to about 50%, about 1% to about 25%, about 1% to about 10%, about 1% to about 5%, about 5% to about 1000%, about 5% to about 750%, about 5% to about 500%, about 5% to about 250%, about 5% to about 150%, or about 5% to about 100%. , about 5% to about 75%, about 5% to about 50%, about 5% to about 25%, about 5% to about 10%, about 10% to about 1000%, about 10% to about 750%, about 10% to about 500%, about 10% to about 250%, about 10% to about 150%, about 10% to about 100%, about 10% to about 75%, about 10% to about 50%, about 10% to about 25%, about 25% to about 1000%, about 25% to about 750%, about 25% to about 500%, about 25% to about 250%, about 25% to about 150%, about 25% to about 100 %, about 25% to about 75%, about 25% to about 50%, about 50% to about 1000%, about 50% to about 750%, about 50% to about 500%, about 50% to about 250%, about 50% to about 150%, about 50% to about 100%, about 100% to about 1000%, about 100% to about 750%, about 100% to about 500%, about 100% to about 250%, about 250% to about 1000%, about 250% to about 750%, about 250% to about 500%, about 500% to about 1000%, about 500% to about 750%, or about 750% to about 1000%.

[0250] In some embodiments, binding of the antibody to the antigen reduces the activity of the antigen by about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 20%, about 25%, about 30%, about 40%, about 50%, about 60%, about 75%, about 80%, about 90%, about 95%, about 99%, about 100%, about 200%, about 250%, about 300%, about 400%, about 500%, about 600%, about 700%, about 750%, about 800%, about 900%, or 1000%, or a range defined by any two of the above values. For example, in some embodiments, antibody binding to an antigen results in a reduction of about 1% to about 1000%, about 1% to about 750%, about 1% to about 500%, about 1% to about 250%, about 1% to about 150%, about 1% to about 100%, about 1% to about 75%, about 1% to about 50%, about 1% to about 25%, about 1% to about 10%, about 1% to about 5%, about 5% to about 1000%, or about 5% to about 750%. , about 5% to about 500%, about 5% to about 250%, about 5% to about 150%, about 5% to about 100%, about 5% to about 75%, about 5% to about 50%, about 5% to about 25%, about 5% to about 10%, about 10% to about 1000%, about 10% to about 750%, about 10% to about 500%, about 10% to about 250%, about 10% to about 150%, about 10% to about 100%, about 10% to about 75%, about 1 0% to approximately 50%, approximately 10% to approximately 25%, approximately 25% to approximately 1000%, approximately 25% to approximately 750%, approximately 25% to approximately 500%, approximately 25% to approximately 250%, approximately 25% to approximately 150%, approximately 25% to approximately 100%, approximately 25% to approximately 75%, approximately 25% to approximately 50%, approximately 50% to approximately 1000%, approximately 50% to approximately 750%, approximately 50% to approximately 500%, approximately 50% to approximately 250%, approximately 50% to The activity of the antigen is reduced by about 150%, about 50% to about 100%, about 100% to about 1000%, about 100% to about 750%, about 100% to about 500%, about 100% to about 250%, about 250% to about 1000%, about 250% to about 750%, about 250% to about 500%, about 500% to about 1000%, about 500% to about 750%, or about 750% to about 1000%.

[0251] In some embodiments, the IL trap-antibody fusion or trap-Fab fusion is about 1 x 10 4 (1 / Ms), approximately 2×10 4 (1 / Ms), approximately 3×104 (1 / Ms), approximately 4 × 10 4 (1 / Ms), approximately 5 × 10 4 (1 / Ms), approximately 6 × 10 4 (1 / Ms), approximately 7 × 10 4 (1 / Ms), approximately 8 × 10 4 (1 / Ms), approximately 9 × 10 4 (1 / Ms), approximately 1×10 5 (1 / Ms), approximately 2×10 5 (1 / Ms), approximately 3 × 10 5 (1 / Ms), approximately 4 × 10 5 (1 / Ms), approximately 5 × 10 5 (1 / Ms), approximately 6 × 10 5 (1 / Ms), approximately 7 × 10 5 (1 / Ms), approximately 8 × 10 5 (1 / Ms), approximately 9 × 10 5 (1 / Ms), approximately 1×10 6 (1 / Ms), approximately 2×10 6 (1 / Ms), approximately 3 × 10 6 (1 / Ms), approximately 4 × 10 6 (1 / Ms), approximately 5 × 10 6 (1 / Ms), approximately 6 × 10 6 (1 / Ms), approximately 7 × 10 6 (1 / Ms), approximately 8 × 10 6 (1 / Ms), approximately 9 × 10 6 (1 / Ms), approximately 1×10 7 (1 / Ms), approximately 2×10 7 (1 / Ms), approximately 3 × 10 7 (1 / Ms), approximately 4 × 10 7 (1 / Ms), approximately 5 × 10 7 (1 / Ms), approximately 6 × 10 7 (1 / Ms), approximately 7 × 10 7 (1 / Ms), approximately 8 × 10 7 (1 / Ms), approximately 9 × 10 7 (1 / Ms), approximately 1×10 8 (1 / Ms), approximately 2×10 8 (1 / Ms), approximately 3 × 10 8 (1 / Ms), approximately 4 × 10 8 (1 / Ms), approximately 5 × 10 8 (1 / Ms), approximately 6 × 10 8 (1 / Ms), approximately 7 × 108 (1 / Ms), approximately 8×10 8 (1 / Ms), approximately 9×10 8 (1 / Ms), approximately 1×10 9 (1 / Ms), approximately 2×10 9 (1 / Ms), approximately 3×10 9 (1 / Ms), approximately 4×10 9 (1 / Ms), approximately 5×10 9 (1 / Ms), approximately 6×10 9 (1 / Ms), approximately 7×10 9 (1 / Ms), approximately 8×10 9 (1 / Ms), or approximately 9 x 10 9 (1 / Ms) or an IL association rate constant (ka) within the range defined by any two of the above values. For example, in some embodiments, the IL trap-antibody fusion or trap-Fab fusion has about 1 x 10 4 ~9×10 9 (1 / Ms), approximately 1×10 4 ~5×10 9 (1 / Ms), approximately 1×10 4 ~1×10 9 (1 / Ms), approximately 1×10 4 ~9×10 8 (1 / Ms), approximately 1×10 4 ~5×10 9 (1 / Ms), approximately 1×10 4 ~1×10 8 (1 / Ms), approximately 1×10 4 ~9×10 7 (1 / Ms), approximately 1×10 4 ~5×10 7 (1 / Ms), approximately 1×10 4 ~1×10 7 (1 / Ms), approximately 1×10 4 ~9×10 6 (1 / Ms), approximately 1×10 4 ~5×10 6 (1 / Ms), approximately 1×10 4 ~1×10 6 (1 / Ms), approximately 1×10 4 ~9×10 5 (1 / Ms), approximately 1×10 4 ~5×105 (1 / Ms), approximately 1×10 4 ~5×10 5 (1 / Ms), approximately 1×10 4 ~1×10 5 (1 / Ms), approximately 1×10 5 ~9×10 9 (1 / Ms), approximately 1×10 5 ~5×10 9 (1 / Ms), approximately 1×10 5 ~1×10 9 (1 / Ms), approximately 1×10 5 ~9×10 8 (1 / Ms), approximately 1×10 5 ~5×10 9 (1 / Ms), approximately 1×10 5 ~1×10 8 (1 / Ms), approximately 1×10 5 ~9×10 7 (1 / Ms), approximately 1×10 5 ~5×10 7 (1 / Ms), approximately 1×10 5 ~1×10 7 (1 / Ms), approximately 1×10 5 ~9×10 6 (1 / Ms), approximately 1×10 5 ~5×10 6 (1 / Ms), approximately 1×10 5 ~1×10 6 (1 / Ms), approximately 1×10 6 ~9×10 9 (1 / Ms), approximately 1×10 6 ~5×10 9 (1 / Ms), approximately 1×10 6 ~1×10 9 (1 / Ms), approximately 1×10 6 ~9×10 8 (1 / Ms), approximately 1×10 6 ~5×10 8 (1 / Ms), approximately 1×10 6 ~1×10 8 (1 / Ms), approximately 1×10 6 ~9×10 7 (1 / Ms), approximately 1×10 6 ~5×10 7 (1 / Ms), approximately 1×10 6 ~1×10 7(1 / Ms), approximately 1×10 7 ~9×10 9 (1 / Ms), approximately 1×10 7 ~5×10 9 (1 / Ms), approximately 1×10 7 ~1×10 9 (1 / Ms), approximately 1×10 7 ~9×10 8 (1 / Ms), approximately 1×10 7 ~5×10 9 (1 / Ms), approximately 1×10 7 ~1×10 8 (1 / Ms), approximately 1×10 8 ~9×10 9 (1 / Ms), approximately 1×10 8 ~5×10 9 (1 / Ms), approximately 1×10 8 ~1×10 9 (1 / Ms), approximately 1×10 8 ~9×10 8 (1 / Ms), or approximately 1 × 10 8 ~5×10 8 The IL has an association rate constant of (1 / Ms).

[0252] In some embodiments, the IL trap-antibody fusion or trap-Fab fusion is about 1 x 10 -1 (1 / s), approximately 2×10 -1 (1 / s), approximately 3×10 -1 (1 / s), approximately 4×10 -1 (1 / s), approximately 5×10 -1 (1 / s), approximately 6×10 -1 (1 / s), approximately 7×10 -1 (1 / s), approximately 8×10 -1 (1 / s), approximately 9×10 -1 (1 / s), approximately 1×10 -2 (1 / s), approximately 2×10 -2 (1 / s), approximately 3×10 -2 (1 / s), approximately 4×10 -2 (1 / s), approximately 5×10 -2 (1 / s), approximately 6×10 -2 (1 / s), approximately 7×10 -2 (1 / s), approximately 8×10 -2 (1 / s), approximately 9×10 -2(1 / s), approximately 1×10 -3 (1 / s), approximately 2 × 10 -3 (1 / s), approximately 3 × 10 -3 (1 / s), approximately 4 × 10 -3 (1 / s), approximately 5 × 10 -3 (1 / s), approximately 6 × 10 -3 (1 / s), approximately 7 × 10 -3 (1 / s), approximately 8 × 10 -3 (1 / s), approximately 9 × 10 -3 (1 / s), approximately 1×10 -4 (1 / s), approximately 2 × 10 -4 (1 / s), approximately 3 × 10 -4 (1 / s), approximately 4 × 10 -4 (1 / s), approximately 5 × 10 -4 (1 / s), approximately 6 × 10 -4 (1 / s), approximately 7 × 10 -4 (1 / s), approximately 8 × 10 -4 (1 / s), approximately 9 × 10 -4 (1 / s), approximately 1×10 -5 (1 / s), approximately 2 × 10 -5 (1 / s), approximately 3 × 10 -5 (1 / s), approximately 4 × 10 -5 (1 / s), approximately 5 × 10 -5 (1 / s), approximately 6 × 10 -5 (1 / s), approximately 7 × 10 -5 (1 / s), approximately 8 × 10 -5 (1 / s), approximately 9 × 10 -5 (1 / s), approximately 1×10 -6 (1 / s), approximately 2 × 10 -6 (1 / s), approximately 3 × 10 -6 (1 / s), approximately 4 × 10 -6 (1 / s), approximately 5 × 10 -6 (1 / s), approximately 6 × 10 -6 (1 / s), approximately 7 × 10 -6 (1 / s), approximately 8 × 10 -6 (1 / s), approximately 9 × 10 -6 (1 / s), approximately 1×10 -7 (1 / s), approximately 2 × 10 -7 (1 / s), approximately 3 × 10 -7 (1 / s), approximately 4 × 10 -7 (1 / s), approximately 5 × 10 -7 (1 / s), approximately 6 × 10-7 (1 / s), approximately 7×10 -7 (1 / s), approximately 8×10 -7 (1 / s), or approximately 9 x 10 -7 (1 / s), or has an IL dissociation rate constant (kd) that is within a range defined by any two of the above values. For example, in some embodiments, the IL trap-antibody fusion or trap-Fab The fusion product is approximately 1 × 10 -1 ~9×10 -7 (1 / s), approximately 1×10 -1 ~5×10 -7 (1 / s), approximately 1×10 -1 ~1×10 -7 (1 / s), approximately 1×10 -1 ~9×10 -6 (1 / s), approximately 1×10 -1 ~5×10 -6 (1 / s), approximately 1×10 -1 ~1×10 -6 (1 / s), approximately 1×10 -1 ~9×10 -5 (1 / s), approximately 1×10 -1 ~5×10 -5 (1 / s), approximately 1×10 -1 ~1×10 -5 (1 / s), approximately 1×10 -1 ~9×10 -4 (1 / s), approximately 1×10 -1 ~5×10 -4 (1 / s), approximately 1×10 -1 ~1×10 -4 (1 / s), approximately 1×10 -1 ~9×10 -3 (1 / s), approximately 1×10 -1 ~5×10 -3 (1 / s), approximately 1×10 -1 ~1×10 -3 (1 / s), approximately 1×10 -1 ~9×10 -2 (1 / s), approximately 1×10 -1 ~5×10 -2 (1 / s), approximately 1×10 -1 ~1×10 -2 (1 / s), approximately 1×10 -2 ~9×10 -7(1 / s), approximately 1×10 -2 ~5×10 -7 (1 / s), approximately 1×10 -1 ~1×10 -7 (1 / s), approximately 1×10 -2 ~9×10 -6 (1 / s), approximately 1×10 -2 ~5×10 -6 (1 / s), approximately 1×10 -2 ~1×10 -6 (1 / s), approximately 1×10 -2 ~9×10 -5 (1 / s), approximately 1×10 -2 ~5×10 -5 (1 / s), approximately 1×10 -2 ~1×10 -5 (1 / s), approximately 1×10 -2 ~9×10 -4 (1 / s), approximately 1×10 -2 ~5×10 -4 (1 / s), approximately 1×10 -2 ~1×10 -4 (1 / s), approximately 1×10 -2 ~9×10 -3 (1 / s), approximately 1×10 -2 ~5×10 -3 (1 / s), approximately 1×10 -2 ~1×10 -3 (1 / s), approximately 1×10 -3 ~9×10 -7 (1 / s), approximately 1×10 -3 ~5×10 -7 (1 / s), approximately 1×10 -3 ~1×10 -7 (1 / s), approximately 1×10 -3 ~9×10 -6 (1 / s), approximately 1×10 -3 ~5×10 -6 (1 / s), approximately 1×10 -3 ~1×10 -6 (1 / s), approximately 1×10 -3 ~9×10 -5 (1 / s), approximately 1×10 -3 ~5×10 -5 (1 / s), approximately 1×10 -3 ~1×10 -5 (1 / s), approximately 1×10 -3 ~9×10-5 (1 / s), approximately 1×10 -3 ~5×10 -4 (1 / s), approximately 1×10 -3 ~1×10 -4 (1 / s), approximately 1×10 -4 ~9×10 -7 (1 / s), approximately 1×10 -4 ~5×10 -7 (1 / s), approximately 1×10 -4 ~1×10 -7 (1 / s), approximately 1×10 -4 ~9×10 -6 (1 / s), approximately 1×10 -4 ~5×10 -6 (1 / s), approximately 1×10 -4 ~1×10 -6 (1 / s), approximately 1×10 -4 ~9×10 -5 (1 / s), approximately 1×10 -4 ~5×10 -5 (1 / s), approximately 1×10 -4 ~1×10 -5 (1 / s), approximately 1×10 -5 ~9×10 -7 (1 / s), approximately 1×10 -5 ~5×10 -7 (1 / s), approximately 1×10 -5 ~1×10 -7 (1 / s), approximately 1×10 -5 ~9×10 -6 (1 / s), approximately 1×10 -5 ~5×10 -6 (1 / s), approximately 1×10 -5 ~1×10 -6 (1 / s), approximately 1×10 -6 ~9×10 -7 (1 / s), approximately 1×10 -6 ~5×10 -7 (1 / s), approximately 1×10 -6 ~1×10 -7 (1 / s), approximately 1×10 -7 ~9×10 -7 (1 / s), or approximately 1×10 -7 ~5×10 -7 The IL dissociation rate constant is (1 / s).

[0253] In some embodiments, the IL trap-antibody fusion or trap-Fab fusion is about 1 x 10 -8 M, approx. 2 x 10 -8 M, about 3 x 10 -8 M, approx. 4 x 10 -8 M, about 5 x 10 -8 M, about 6 x 10 -8 M, about 7 x 10 -8 M, about 8 x 10 -8 M, about 9 x 10 -8 M, about 1 x 10 -9 M, approx. 2 x 10 -9 M, about 3 x 10 -9 M, approx. 4 x 10 -9 M, about 5 x 10 -9 M, about 6 x 10 -9 M, about 7 x 10 -9 M, about 8 x 10 -9 M, about 9 x 10 -9 M, about 1 x 10 -10 M, approx. 2 x 10 -10 M, about 3 x 10 -10 M, approx. 4 x 10 -10 M, about 5 x 10 -10 M, about 6 x 10 -10 M, about 7 x 10 -10 8×10 -10 M, about 9 x 10 -10 M, about 1 x 10 -11 M, approx. 2 x 10 -11 M, about 3 x 10 -11 M, approx. 4 x 10 -11 M, about 5 x 10 -11 M, about 6 x 10 -11 M, about 7 x 10 -11 M, about 8 x 10 -11 M, about 9 x 10 -11 M, about 1 x 10 -12 M, approx. 2 x 10 -12 M, about 3 x 10 -12 M, approx. 4 x 10 -12 M, about 5 x 10 -12 M, about 6 x 10 -12 M, about 7 x 10 -12 M, about 8 x 10 -12 M, about 9 x 10 -12 M, about 1 x 10 -13 M, approx. 2 x 10 -13 M, about 3 x 10 -13M, approx. 4 x 10 -13 M, about 5 x 10 -13 M, about 6 x 10 -13 M, about 7 x 10 -13 M, about 8 x 10 -13 M, or 9 x 10 -13 M, or defined by any two of the above values. For example, in some embodiments, the IL trap-antibody fusion or trap-Fab fusion has an IL equilibrium dissociation constant that is within the range of about 1 x 10 -8 ~9×10 -13 M, about 1 x 10 -8 ~5×10 -13 M, about 1 x 10 -8 ~1×10 -13 M, about 1 x 10 -8 ~9×10 -12 M, about 1 x 10 -8 ~5×10 -12 M, about 1 x 10 -8 ~1×10 -12 M, about 1 x 10 -8 ~9×10 -11 M, about 1 x 10 -8 ~5×10 -11 M, about 1 x 10 -8 ~1×10 -11 M, about 1 x 10 -8 ~9×10 -10 M, about 1 x 10 -8 ~5×10 -10 M, about 1 x 10 -8 ~1×10 -10 M, about 1 x 10 -8 ~9×10 -9 M, about 1 x 10 -8 ~5×10 -9 M, about 1 x 10 -8 ~1×10 -9 M, about 1 x 10 -8 ~9×10 -8 M, about 1 x 10 -8 ~5×10 -8 M, about 1 x 10 -9 ~9×10 -12 M, about 1 x 10 -9 ~5×10 -12 M, about 1 x 10 -9 ~1×10 -12M, about 1 x 10 -9 ~9×10 -11 M, about 1 x 10 -9 ~5×10 -11 M, about 1 x 10 -9 ~1×10 -11 M, about 1 x 10 -9 ~9×10 -10 M, about 1 x 10 -9 ~5×10 -10 M, about 1 x 10 -9 ~1×10 -10 M, about 1 x 10 -9 ~9×10 -9 M, about 1 x 10 -9 ~5×10 -9 M, about 1 x 10 -10 ~9×10 -12 M, about 1 x 10 -10 ~5×10 -12 M, about 1 x 10 -10 ~1×10 -12 M, about 1 x 10 -10 ~9×10 -11 M, about 1 x 10 -10 ~5×10 -11 M, about 1 x 10 -10 ~1×10 -11 M, about 1 x 10 -10 ~9×10 -10 M, about 1 x 10 -10 ~5×10 -10 M, about 1 x 10 -11 ~9×10 -12 M, about 1 x 10 -11 ~5×10 -12 M, about 1 x 10 -11 ~1×10 -12 M, about 1 x 10 -11 ~9×10 -11 M, about 1 x 10 -11 ~5×10 -11 M, about 1 x 10 -12 ~9×10 -12 M, or approximately 1 x 10 -12 ~5×10 -12 The IL has an equilibrium dissociation constant of M.

[0254] polymer A "polymer" is a molecule composed of many repeating subunits. These subunits, sometimes called "monomers," can be the same or different. Both natural and synthetic polymers exist. DNA, proteins, and complex carbohydrates are examples of natural polymers. Polystyrene and polyacrylamide are examples of synthetic polymers. A polymer composed of repeating units of a single type of monomer is called a homopolymer. A polymer composed of two or more types of monomer is called a copolymer, or sometimes a heteropolymer. A copolymer in which certain monomer types are clustered together is sometimes called a block copolymer. Polymers can be linear or branched. When a polymer is branched, the polymer chains that share a common origin can be called polymer arms.

[0255] An "initiator" is a compound capable of serving as a substrate for one or more rounds of polymerization with a monomer or comonomer as described herein. The polymerization can be conventional free radical polymerization, or preferably, controlled / "living" radical polymerization, such as atom transfer radical polymerization (ATRP), reversible addition-fragmentation-termination (RAFT) polymerization, or nitroxide-mediated polymerization (NMP). The polymerization can be "quasi" controlled polymerization, such as degenerative transfer. Initiators suitable for ATRP contain one or more labile bonds that can undergo homolytic cleavage to form an initiator fragment I, a radical capable of initiating radical polymerization, and a radical scavenger I', which reacts with radicals on a growing polymer chain to reversibly terminate the polymerization. The radical scavenger I' is typically a halogen but can also be an organic moiety such as a nitrile. In some embodiments of the present invention, the initiator contains one ...

Claims

1. A multivalent trap-antibody fusion and / or multivalent trap-Fab fusion comprising a trap and an antibody or a fragment thereof, The antibody or fragment thereof a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; a light chain variable region (VL) comprising a VL CDR1, a VL CDR2, and a VL CDR3; the trap and the antibody or fragment thereof are connected in series by a linker; the trap-antibody fusion and / or trap-Fab fusion comprises both a cytokine binding site and an antigen binding site; the cytokine and antigen binding sites are located at separate locations on the trap-antibody fusion and / or trap-Fab fusion; Multivalent trap-antibody fusions and / or multivalent trap-Fab fusions.

2. A multivalent interleukin (IL) trap-antibody and / or multivalent IL trap-Fab fusion comprising an IL trap and an antibody or fragment thereof, The antibody or fragment thereof a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; a light chain variable region (VL) comprising a VL CDR1, a VL CDR2, and a VL CDR3; the IL trap comprises an IL receptor and an IL accessory protein; the IL trap and the antibody or fragment thereof are connected in series by a linker; the IL-trap-antibody fusion and / or IL-trap-Fab fusion comprises both an IL-binding site and an antigen-binding site; the IL-binding site and the antigen-binding site are located at separate locations on the trap-antibody fusion and / or trap-Fab fusion; Multivalent IL-trap-antibody and / or multivalent IL-trap-Fab fusions.

3. A multivalent interleukin (IL) trap-antibody fusion comprising an IL trap and an antibody, the IL trap comprises an IL receptor and an IL accessory protein; The antibody a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; a light chain variable region (VL) comprising a VL CDR1, a VL CDR2, and a VL CDR3; the interleukin trap and the antibody are connected in series by a linker; the interleukin trap-antibody fusion contains both an IL-binding site and an antigen-binding site; Binding of the IL trap-antibody fusion to IL inhibits IL signaling; The binding of the IL-trap-antibody fusion to an antigen inhibits antigen activity. Multivalent interleukin (IL) trap-antibody fusions.

4. A multivalent interleukin (IL) trap-Fab fusion comprising an IL trap and an antigen-binding fragment (Fab fragment), the IL trap comprises an IL receptor and an IL accessory protein; The Fab is a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; a light chain variable region (VL) comprising a VL CDR1, a VL CDR2, and a VL CDR3; the IL trap and the Fab are connected in series by a linker; The IL-trap-Fab fusion contains both an IL-binding site and an antigen-binding site; the IL-binding site and the antigen-binding site are located at separate locations on the trap-Fab fusion; Multivalent IL-Trap-Fab fusions.

5. A multivalent interleukin (IL) trap-Fab fusion comprising an IL trap and an antigen-binding fragment (Fab fragment), The IL trap and the Fab are connected in series by a linker. Multivalent interleukin (IL) trap-Fab fusions.

6. A multivalent VHH-antibody fusion and / or a multivalent VHH-Fab fusion comprising a VHH and an antibody or a fragment thereof, The antibody or fragment thereof a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; and a heavy chain variable region (VH) comprising: VH CDR1, VH CDR2, and VH CDR3; a light chain variable region (VL) comprising a VL CDR1, a VL CDR2, and a VL CDR3; the VHH and the antibody or fragment thereof are connected in series by a linker; the VHH-antibody fusion and / or VHH-Fab fusion comprises both a cytokine-binding site and an antigen-binding site; the cytokine and antigen binding sites are located at separate locations on the VHH-antibody fusion and / or VHH-Fab fusion, Multivalent VHH-antibody and / or VHH-Fab fusions.

7. A multivalent VHH-antibody fusion and / or a multivalent VHH-Fab fusion comprising a VHH and an antibody or a fragment thereof, The antibody or fragment thereof a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; and a heavy chain variable region (VH) comprising: VH CDR1, VH CDR2, and VH CDR3; a light chain variable region (VL) comprising a VL CDR1, a VL CDR2, and a VL CDR3; the VHH and the antibody or fragment thereof are connected in series by a linker; the VHH-antibody fusion and / or VHH-Fab fusion comprises both a cytokine-binding site and an antigen-binding site; the cytokine and antigen binding sites are located at separate locations on the VHH-antibody fusion and / or VHH-Fab fusion, Multivalent VHH-antibody and / or VHH-Fab fusions.

8. 1. A method of inhibiting interleukin signaling in a subject, comprising: administering an interleukin trap-antibody fusion; The fusion product is IL trap and an antibody; The antibody a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; a light chain variable region (VL) comprising a VL CDR1, a VL CDR2, and a VL CDR3; the IL trap-antibody fusion comprises an IL binding site and an antigen binding site; Binding of the IL trap-antibody fusion to IL inhibits IL signaling; The binding of the IL-trap-antibody fusion to an antigen inhibits antigen activity. method.

9. 1. A method of inhibiting cytokine signaling in a subject, comprising: administering a cytokine trap-antibody fusion; The fusion product is Cytokine traps and an antibody; The antibody a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; a light chain variable region (VL) comprising a VL CDR1, a VL CDR2, and a VL CDR3; the cytokine trap-antibody fusion comprises a cytokine binding site and an antigen binding site; the cytokine trap-antibody fusion binds to a cytokine, thereby inhibiting cytokine signaling; The cytokine trap-antibody fusion binds to an antigen, thereby inhibiting antigen activity. method.

10. The trap-antibody or trap-Fab fusion of any one of claims 1 to 9, which is bivalent.

11. The trap-antibody or trap-Fab fusion of any one of claims 1 to 10, which is tetravalent.

12. The trap-antibody fusion of any one of claims 1 to 11, comprising two traps and two antibody arms.

13. The trap-antibody or trap-Fab fusion of any one of claims 1 to 12, conjugated to a polymer.

14. The trap-antibody or trap-Fab fusion of any one of claims 1 to 13, further comprising a signal peptide.

15. The trap-antibody or trap-Fab fusion of any one of claims 1 to 14, which is capable of binding to a cytokine and an antigen simultaneously.

16. A cytokine trap having a cytokine binding affinity of about 0.01 pM to about 10 nM. The trap-antibody or trap-Fab fusion of any one of claims 1 to 15, comprising:

17. The trap-antibody or trap-Fab fusion of any one of claims 1 to 16, comprising a cytokine trap with a cytokine binding affinity of about 0.01 pM to about 5 nM.

18. The trap-antibody or trap-Fab fusion of any one of claims 1 to 17, comprising a cytokine trap with a cytokine binding affinity of about 0.01 pM to about 1 nM.

19. The trap-antibody or trap-Fab fusion of any one of claims 1 to 18, comprising a cytokine trap with a cytokine binding affinity of about 0.01 pM to about 100 pM.

20. The trap-antibody or trap-Fab fusion of any one of claims 1 to 19, comprising an antibody having an antigen-binding affinity of about 0.01 pM to about 500 pM.

21. The trap-antibody or trap-Fab fusion of any one of claims 1 to 20, comprising a cytokine trap with a cytokine binding affinity of about 0.01 pM to about 100 pM.

22. 22. The trap-antibody or trap-Fab fusion of any one of claims 1 to 21, comprising a cytokine trap having a cytokine binding affinity of about 0.01 pM to about 100 pM and an antibody or Fab having an antigen binding affinity of about 0.01 pM to about 500 pM.

23. The trap-antibody or trap-Fab fusion of any one of claims 1 to 22, wherein the cytokine trap and antibody or Fab simultaneously bind to the cytokine and antigen.

24. The trap-antibody or trap-Fab fusion of any one of claims 1 to 23, wherein the trap is an IL-1 trap.

25. The trap-antibody or trap-Fab fusion of any one of claims 1 to 24, wherein the trap is an IL-6 trap.

26. The trap-antibody or trap-Fab fusion of any one of claims 1 to 25, wherein the trap is an IL-33 trap.

27. The trap-antibody or trap-Fab fusion of any one of claims 1 to 26, wherein the trap is a TNFα trap.

28. The trap-antibody or trap-Fab fusion of any one of claims 1 to 27, wherein the trap is a VEGF trap.

29. The trap-antibody or trap-Fab fusion of any one of claims 1 to 28, wherein the IL receptor protein is encoded by IL1R1.

30. The method of any one of claims 1 to 29, wherein the IL receptor protein is ST2. Trap-antibody fusion or trap-Fab fusion.

31. The IL trap-antibody or trap-Fab fusion of any one of claims 1 to 30, wherein the IL accessory protein is IL1RAcP.

32. The IL trap-antibody or trap-Fab fusion of any one of claims 1 to 31, wherein the IL accessory protein is gp130 (IL6Rβ).

33. The IL trap-antibody or trap-Fab fusion of any one of claims 1 to 32, wherein said antibody or Fab is an anti-HTRA1 antibody or Fab.

34. The IL-trap-antibody fusion of any one of claims 1 to 33, wherein the antibody or Fab is an IL-6 antibody or Fab.

35. 35. The IL trap-antibody or trap-Fab fusion of any one of claims 1 to 34, comprising an IL trap that is an IL-1 trap and an antibody that is an anti-HTRA1 antibody.

36. an IL-1 trap, which is an IL-1 trap; an antibody that is an anti-HTRA1 antibody; The IL-1 trap comprises IL1R1 and IL1RacP; The IL trap-antibody fusion of any one of claims 1 to 35.

37. an IL-1 trap, which is an IL-1 trap; an antibody or Fab that is an anti-HTRA1 antibody; The IL-1 trap comprises IL1R1 and IL1RacP; the IL-1 trap has an IL-1 binding affinity of about 0.01 pM to about 100 pM; the anti-HTRA1 antibody has an HTRA1 binding affinity of about 0.01 pM to about 500 pM; The IL trap-antibody fusion of any one of claims 1 to 36.

38. an IL-1 trap, which is an IL-1 trap; an antibody that is an anti-HTRA1 antibody; The IL-1 trap comprises IL1R1 and IL1RAcP; the IL-1 trap has an IL-1 binding affinity of less than about 1 nM; the anti-HTRA1 antibody has an HTRA1 binding affinity of less than about 1 nM; The IL trap-antibody fusion of any one of claims 1 to 37.

39. an IL-1 trap, which is an IL-1 trap; an antibody that is an anti-HTRA1 antibody; Including, The IL-1 trap comprises IL1R1 and IL1RAcP; the IL-1 trap has an IL-1 binding affinity of about 0.01 pM to about 100 pM; the anti-HTRA1 antibody has an HTRA1 binding affinity of about 0.01 pM to about 500 pM; The IL trap-antibody fusion of any one of claims 1 to 38.

40. IL-trap, where the IL-trap-antibody fusion is IL-33 trap, and anti-HTRA1 and an antibody that is an antibody.

41. an IL-trap, which is an IL-33 trap; an antibody or Fab that is an anti-HTRA1 antibody; The IL-33 trap comprises ST2 and IL1RAcP. The IL trap-antibody fusion of any one of claims 1 to 40.

42. IL-trap-antibody fusion an IL-33 trap, an IL-trap; an antibody or Fab that is an anti-HTRA1 antibody; Including; The IL-33 trap comprises ST2 and IL1RAcP; the IL-33 trap has an IL-33 binding affinity of less than about 1 nM; the anti-HTRA1 antibody has an HTRA1 binding affinity of less than about 1 nM; The IL trap-antibody of any one of claims 1 to 41.

43. The trap-antibody fusion or trap-Fab fusion an IL-trap, which is an IL-33 trap; an antibody that is an anti-HTRA1 antibody; Including; the IL-33 trap comprises ST2 and IL1RAcP; the IL-33 trap has an IL-33 binding affinity of about 0.01 pM to about 100 pM; the anti-HTRA1 antibody has an HTRA1 binding affinity of about 0.01 pM to about 500 pM; The IL trap-antibody fusion of any one of claims 1 to 42.

44. IL-trap-antibody fusion an IL-trap, which is an IL-33 trap; an antibody that is an anti-HTRA1 antibody; Including; the IL-33 trap comprises ST2 and IL1RAcP; the IL-33 trap has an IL-33 binding affinity of about 0.01 pM to about 100 pM; the anti-HTRA1 antibody has an HTRA1 binding affinity of about 0.01 pM to about 500 pM; The IL trap-antibody of any one of claims 1 to 43.

45. 45. The IL trap-antibody fusion of any one of claims 1 to 44, wherein the trap-antibody fusion or trap-Fab fusion comprises an IL trap that is an IL-6 trap and an antibody that is an anti-HTRA1 antibody.

46. IL-trap-antibody fusion or trap-Fab IL-trap, which is an IL-6 trap; an antibody that is an anti-HTRA1 antibody; Including; The IL-6 trap comprises gp130 (IL6Rβ) and IL-6Rα; The IL trap-antibody fusion of any one of claims 1 to 45.

47. The trap-antibody fusion or trap-Fab fusion IL-trap, which is an IL-6 trap; an antibody that is an anti-HTRA1 antibody; Including; The IL-6 trap comprises gp130 (IL6Rb) and IL-6Rα; the IL-6 trap has an IL-6 binding affinity of less than about 1 nM; the anti-HTRA1 antibody has an HTRA1 binding affinity of less than about 1 nM; 47. The IL trap-antibody fusion or trap-Fab of any one of claims 1 to 46.

48. The trap-antibody fusion or trap-Fab fusion IL-trap, which is an IL-6 trap; an antibody that is an anti-HTRA1 antibody; Including; The IL-6 trap comprises gp130 (IL6Rβ) and IL-6Rα; the IL-6 trap has an IL-6 binding affinity of about 0.01 pM to about 500 pM; the anti-HTRA1 antibody has an HTRA1 binding affinity of about 5 pM to about 500 pM; The IL trap-antibody fusion of any one of claims 1 to 47.

49. The trap-antibody fusion or trap-Fab fusion IL-trap, which is an IL-6 trap; an antibody or Fab that is an anti-HTRA1 antibody; Including; The IL-6 trap comprises gp130 (IL-6Rβ) and IL-6Rα; the IL-6 trap has an IL-6 binding affinity of about 0.01 pM to about 100 pM; the anti-HTRA1 antibody has an HTRA1 binding affinity of about 0.01 pM to about 500 pM; 49. The IL trap-antibody or fusion of any one of claims 1 to 48.

50. 50. The IL trap-antibody fusion of any one of claims 1 to 49, wherein the heavy chain of the trap-antibody fusion or trap-Fab fusion comprises an IL receptor protein linked to an antibody VH; and the light chain of the trap-antibody fusion or trap-Fab fusion comprises an IL accessory protein linked to an antibody VL.

51. 51. The IL trap-antibody fusion of any one of claims 1 to 50, wherein the heavy chain of the trap-antibody fusion or trap-Fab fusion comprises an IL receptor protein linked to an antibody VL; and the light chain of the trap-antibody fusion or trap-Fab fusion comprises an IL accessory protein linked to an antibody VH.

52. 52. The IL trap-antibody or trap-Fab fusion of any one of claims 1 to 51, wherein the heavy and / or light chain of the trap-antibody or trap-Fab comprises a receptor protein selected from the group comprising SEQ ID NOs: 1 to 15 and SEQ ID NOs: 67 to 71.

53. 53. The IL trap-antibody or trap-Fab fusion of any one of claims 1 to 52, wherein the heavy and / or light chain of the trap-antibody or trap-Fab comprises a linker that is a linker in SEQ ID NOs: 24 to 27.

54. 54. The IL trap-antibody or trap-Fab fusion of any one of claims 1 to 53, comprising an antibody in which the heavy and / or light chain of the trap-antibody or trap-Fab is an antibody selected from the group comprising SEQ ID NOs: 28 to 47 and SEQ ID NOs: 64 to 66.

55. 55. The IL trap-antibody or trap-Fab fusion of any one of claims 1 to 54, wherein the light chain of the trap-antibody or trap-Fab comprises a signal peptide selected from the group comprising SEQ ID NOs: 16-23 and 72-73.

56. 56. The IL trap-antibody or trap-Fab fusion of any one of claims 1 to 55, wherein binding of the IL trap to an IL reduces the activity of the IL.

57. 57. The IL trap-antibody or trap-Fab fusion of any one of claims 1 to 56, wherein binding of the antibody or Fab to an antigen inhibits the activity of the antigen.

58. 58. An IL trap-antibody fusion or trap-Fab fusion according to any one of claims 1 to 57, wherein the IL trap binds to an IL and the antibody or Fab binds to an antigen, thereby inhibiting the activity of the IL and the antigen.

59. 59. The IL trap-antibody or trap-Fab fusion of any one of claims 1 to 58, wherein the IL trap sequentially binds to an IL and the antibody or Fab sequentially binds to an antigen, thereby inhibiting the activity of the IL and the antigen.

60. 60. An IL trap-antibody fusion according to any one of claims 1 to 59, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 17, a trap of SEQ ID NO: 1, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 38, and a CH of SEQ ID NO:

28.

61. 61. An IL trap-antibody fusion according to any one of claims 1 to 60, wherein the heavy chain of the trap-antibody fusion comprises a trap of sequence number 1, a linker of sequence number 25, a VH of sequence number 38, and a CH of sequence number 28.

62. 62. The IL trap-antibody fusion or trap Fab fusion of any one of claims 1 to 61, wherein the light chain of the trap-antibody fusion or trap Fab fusion comprises a signal peptide of SEQ ID NO: 18, a trap of SEQ ID NO: 2, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 44, and a CL of SEQ ID NO:

29.

63. 63. The IL trap-antibody fusion or trap Fab fusion of any one of claims 1 to 62, wherein the light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 44, and a CL that is SEQ ID NO:

29.

64. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 17, a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 38, and a CH that is SEQ ID NO: 28; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 18, a trap of SEQ ID NO: 2, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 44, and a CL of SEQ ID NO:

29. The IL trap-antibody fusion of any one of claims 1 to 63.

65. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 38, and a CH that is SEQ ID NO: 28; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 44, and a CL that is SEQ ID NO:

29. The IL trap-antibody fusion of any one of claims 1 to 64.

66. 66. An IL trap-Fab fusion according to any one of claims 1 to 65, wherein the heavy chain of the trap-Fab fusion comprises a signal peptide of SEQ ID NO: 17, a trap of SEQ ID NO: 1, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

46.

67. 67. An IL trap-Fab fusion according to any one of claims 1 to 66, wherein the heavy chain of the trap-Fab fusion comprises a trap of SEQ ID NO: 1, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

46.

68. 68. The IL trap-antibody fusion or trap-Fab fusion of any one of claims 1 to 67, wherein the light chain of the trap-antibody fusion or trap-Fab fusion comprises a signal peptide of SEQ ID NO: 18, a trap of SEQ ID NO: 2, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29.

69. 69. The IL trap-antibody fusion or trap-Fab fusion of any one of claims 1 to 68, wherein the light chain of the trap-antibody fusion or trap-Fab fusion comprises a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

70. the heavy chain of the trap-Fab fusion comprises a signal peptide that is SEQ ID NO: 17, a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 46; and The light chain of the trap-Fab fusion comprises a signal peptide of SEQ ID NO: 18, a trap of SEQ ID NO: 2, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29.

70. The IL trap-Fab fusion of any one of claims 1 to 69.

71. the heavy chain of the trap-Fab fusion comprises a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 46; and The light chain of the trap-Fab fusion comprises a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

71. The IL trap-Fab fusion of any one of claims 1 to 70.

72. The trap-antibody fusion of any one of claims 1 to 71, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 17, a trap of SEQ ID NO: 1, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

65.

73. The trap-antibody fusion of any one of claims 1 to 72, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

65.

74. The trap-antibody fusion of any one of claims 1 to 73, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 18, a trap of SEQ ID NO: 2, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

66.

75. The trap-antibody fusion of any one of claims 1 to 74, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

66.

76. 76. The trap-antibody fusion of any one of claims 1 to 75, wherein the light chain of the trap-antibody or fusion comprises a signal peptide that is SEQ ID NO: 16, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

77. The trap-antibody or fusion of any one of claims 1 to 76, wherein the light chain of the trap-antibody or fusion comprises a VL that is SEQ ID NO:39 and a CL that is SEQ ID NO:

29.

78. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 17, a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65; the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 18, a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 66; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 16, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 77.

79. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65; the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:2, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:66; and the light chain of the trap-antibody fusion comprises a VL that is SEQ ID NO: 39 and a CL that is SEQ ID NO: 29; The trap-antibody fusion of any one of claims 1 to 78.

80. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 17, a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65; and The heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 18, a trap of SEQ ID NO: 2, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

66. The trap-antibody fusion of any one of claims 1 to 79.

81. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65; and The heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

66. The trap-antibody fusion of any one of claims 1 to 80.

82. The trap-antibody fusion of any one of claims 1 to 81, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 18, a trap of SEQ ID NO: 2, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

65.

83. Any of claims 1 to 82, wherein the heavy chain of the trap-antibody fusion comprises a trap of SEQ ID NO: 2, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

65. The trap-antibody fusion of any one of claims 1 to 4.

84. The trap-antibody fusion of any one of claims 1 to 83, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 17, a trap of SEQ ID NO: 1, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

66.

85. The trap-antibody fusion of any one of claims 1 to 84, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

66.

86. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 18, a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65; the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 17, a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 66; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 16, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 85.

87. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:2, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65; the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 66; and the light chain of the trap-antibody fusion comprises a VL that is SEQ ID NO: 39 and a CL that is SEQ ID NO: 29; The trap-antibody fusion of any one of claims 1 to 86.

88. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 18, a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65; and The heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 17, a trap of SEQ ID NO: 1, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

66. The trap-antibody fusion of any one of claims 1 to 87.

89. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:2, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65; and The heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

66. The trap-antibody fusion of any one of claims 1 to 88.

90. The trap-antibody fusion of any one of claims 1 to 89, wherein the heavy chain of the trap-antibody fusion or trap-Fab fusion comprises a signal peptide of SEQ ID NO: 17, a trap of SEQ ID NO: 1, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

64.

91. The trap-antibody fusion of any one of claims 1 to 90, wherein the heavy chain of the trap-antibody fusion or trap-Fab fusion comprises a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

64.

92. The trap-antibody fusion or trap-Fab fusion of any one of claims 1 to 91, wherein the light chain of the trap-antibody fusion or trap-Fab fusion comprises a signal peptide of SEQ ID NO: 18, a trap of SEQ ID NO: 2, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29.

93. The trap-antibody fusion or trap-Fab fusion of any one of claims 1 to 92, wherein the light chain of the trap-antibody fusion or trap-Fab fusion comprises a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

94. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 17, a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 18, a trap of SEQ ID NO: 2, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 93.

95. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 1, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 64; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 2, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 94.

96. The trap-antibody fusion of any one of claims 1 to 95, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 67, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

64.

97. The trap-antibody fusion of any one of claims 1 to 96, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 67, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

64.

98. The trap-antibody fusion of any one of claims 1 to 97, wherein the light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 67, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29.

99. The trap-antibody fusion of any one of claims 1 to 98, wherein the light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 67, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

100. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:72, a trap of SEQ ID NO:67, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 99.

101. The heavy chain of the trap-antibody fusion is a trap of SEQ ID NO:67 and a ligase of SEQ ID NO:

25. a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 64; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 100.

102. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 16, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 101.

103. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and the light chain of the trap-antibody fusion comprises a VL that is SEQ ID NO: 39 and a CL that is SEQ ID NO: 29; The trap-antibody fusion of any one of claims 1 to 102.

104. The trap-antibody fusion of any one of claims 1 to 103, wherein the heavy chain of the trap-antibody comprises a signal peptide of SEQ ID NO: 16, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

64.

105. The trap-antibody fusion of any one of claims 1 to 104, wherein the heavy chain of the trap-antibody comprises a VH of SEQ ID NO: 30 and a CH of SEQ ID NO:

64.

106. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:72, a trap of SEQ ID NO:67, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 105.

107. the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 64; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 106.

108. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 28; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:72, a trap of SEQ ID NO:67, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 107.

109. the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 28; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 108.

110. The trap-antibody fusion of any one of claims 1 to 109, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 67, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

65.

111. The trap-antibody fusion of any one of claims 1 to 110, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 67, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

65.

112. The trap-antibody fusion of any one of claims 1 to 111, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 16, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

66.

113. The trap-antibody fusion of any one of claims 1 to 112, wherein the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30 and a CH that is SEQ ID NO:

66.

114. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65; the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 66; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:72, a trap of SEQ ID NO:67, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 113.

115. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65; the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 66; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 114.

116. The trap-antibody fusion of any one of claims 1 to 115, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

65.

117. The trap-antibody fusion of any one of claims 1 to 116, wherein the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30 and a CH that is SEQ ID NO:

65.

118. The trap-antibody fusion of any one of claims 1 to 117, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 67, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

66.

119. The trap-antibody fusion of any one of claims 1 to 118, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 67, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

66.

120. The heavy chain of the trap-antibody fusion contains a signal peptide of SEQ ID NO: 16, a signal peptide of SEQ ID NO: 30 a VH that is, and a CH that is SEQ ID NO: 65; the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:66; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:72, a trap of SEQ ID NO:67, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 119.

121. the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 65; the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:66; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:67, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 120.

122. The trap-antibody fusion of any one of claims 1 to 121, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 68, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

64.

123. The trap-antibody fusion of any one of claims 1 to 122, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 68, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

64.

124. The trap-antibody fusion of any one of claims 1 to 123, wherein the light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 68, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29.

125. The trap-antibody of any one of claims 1 to 124, wherein the trap-antibody or light chain comprises a trap that is SEQ ID NO: 68, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

126. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:72, a trap of SEQ ID NO:68, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 125.

127. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 126.

128. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 16, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 127.

129. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and the light chain of the trap-antibody fusion comprises a VL that is SEQ ID NO: 39 and a CL that is SEQ ID NO: 29; The trap-antibody fusion of any one of claims 1 to 128.

130. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 28; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:72, a trap of SEQ ID NO:68, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 129.

131. the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 28; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 130.

132. The trap-antibody fusion of any one of claims 1 to 131, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 68, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

65.

133. The trap-antibody fusion of any one of claims 1 to 132, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 68, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

65.

134. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65; the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 66; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:72, a trap of SEQ ID NO:68, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 133.

135. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65; the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 66; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 134.

136. The heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a signal peptide of SEQ ID NO: 68 The trap-antibody fusion of any one of claims 1 to 135, comprising a trap which is SEQ ID NO: 25, a linker which is SEQ ID NO: 30, and a CH which is SEQ ID NO:

66.

137. The trap-antibody fusion of any one of claims 1 to 136, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 68, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

66.

138. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65; the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:66; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:72, a trap of SEQ ID NO:68, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 137.

139. the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 65; the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:66; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:68, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 138.

140. The trap-antibody fusion of any one of claims 1 to 139, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 73, a trap of SEQ ID NO: 69, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

64.

141. The trap-antibody fusion of any one of claims 1 to 140, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 69, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

64.

142. The trap-antibody fusion of any one of claims 1 to 141, wherein the light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:73, a trap of SEQ ID NO:69, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29.

143. The trap-antibody fusion of any one of claims 1 to 142, wherein the light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 69, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

144. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:73, a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:73, a trap of SEQ ID NO:69, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 143.

145. The heavy chain of the trap-antibody fusion is a trap of SEQ ID NO:69, a lysine of SEQ ID NO:25 a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 64; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 144.

146. The trap-antibody fusion of any one of claims 1 to 145, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 69, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

64.

147. The trap-antibody fusion of any one of claims 1 to 146, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 69, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

64.

148. The trap-antibody of any one of claims 1 to 147, wherein the light chain of the trap-antibody comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 69, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29.

149. The trap-antibody fusion of any one of claims 1 to 148, wherein the light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 69, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

150. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:72, a trap of SEQ ID NO:69, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 149.

151. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 150.

152. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:73, a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 16, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 151.

153. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and the light chain of the trap-antibody fusion comprises a VL that is SEQ ID NO: 39 and a CL that is SEQ ID NO: 29; The trap-antibody fusion of any one of claims 1 to 152.

154. The heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 69, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a VH of SEQ ID NO:

64. and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 16, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 153.

155. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:72, a trap of SEQ ID NO:69, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 154.

156. the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 64; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 155.

157. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 28; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:73, a trap of SEQ ID NO:69, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 156.

158. the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 28; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 157.

159. The trap-antibody fusion of any one of claims 1 to 158, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 69, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

65.

160. The trap-antibody fusion of any one of claims 1 to 159, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 69, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

65.

161. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65; the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 66; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:72, a trap of SEQ ID NO:69, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 160.

162. The heavy chain of the trap-antibody fusion is a trap of SEQ ID NO:69, a lysine of SEQ ID NO:25 a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65; the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 66; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 161.

163. The trap-antibody fusion of any one of claims 1 to 162, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 69, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

66.

164. The trap-antibody fusion of any one of claims 1 to 163, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 69, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

66.

165. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65; the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:66; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO:72, a trap of SEQ ID NO:69, a linker of SEQ ID NO:25, a VL of SEQ ID NO:39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 164.

166. the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 65; the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:66; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:69, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 165.

167. The trap-antibody fusion of any one of claims 1 to 166, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 73, a trap of SEQ ID NO: 70, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

64.

168. The trap-antibody fusion of any one of claims 1 to 167, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

64.

169. The trap-antibody fusion or trap-Fab fusion of any one of claims 1 to 168, wherein the light chain of the trap-antibody fusion or trap-Fab fusion comprises a signal peptide that is SEQ ID NO: 73, a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

170. The trap-antibody fusion or trap-Fab fusion of any one of claims 1 to 169, wherein the light chain of the trap-antibody fusion or trap-Fab fusion comprises a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29.

171. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:73, a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 73, a trap of SEQ ID NO: 70, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 170.

172. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 171.

173. The trap-antibody fusion of any one of claims 1 to 172, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 70, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

64.

174. The trap-antibody fusion of any one of claims 1 to 173, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

64.

175. The trap-antibody fusion of any one of claims 1 to 174, wherein the light chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

176. The trap-antibody fusion of any one of claims 1 to 175, wherein the light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

177. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 70, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 176.

178. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 177.

179. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:73, a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and the light chain of the trap-Fab fusion comprises a signal peptide of SEQ ID NO: 16, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO: 29; The trap-antibody fusion of any one of claims 1 to 178.

180. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and the light chain of the trap-Fab fusion comprises a VL of SEQ ID NO: 39 and a CL of SEQ ID NO: 29; The trap-antibody fusion of any one of claims 1 to 179.

181. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 16, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 180.

182. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and the light chain of the trap-antibody fusion comprises a VL that is SEQ ID NO: 39 and a CL that is SEQ ID NO: 29; The trap-antibody fusion of any one of claims 1 to 181.

183. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 73, a trap of SEQ ID NO: 70, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 182.

184. the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 64; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 183.

185. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 70, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 184.

186. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 28; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 73, a trap of SEQ ID NO: 70, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 185.

187. the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 28; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 186.

188. The trap-antibody fusion of any one of claims 1 to 187, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 70, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

65.

189. The trap-antibody fusion of any one of claims 1 to 188, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

65.

190. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65; the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 66; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 70, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 189.

191. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65; the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 66; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 190.

192. The trap-antibody fusion of any one of claims 1 to 191, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 70, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

66.

193. The trap-antibody fusion of any one of claims 1 to 192, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

66.

194. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65; the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:66; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 70, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 193.

195. the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 65; the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:70, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:66; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 70, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 194.

196. The trap-antibody fusion of any one of claims 1 to 195, wherein the heavy chain of the trap-antibody fusion or trap-Fab fusion comprises a signal peptide of SEQ ID NO: 73, a trap of SEQ ID NO: 71, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

64.

197. The trap-antibody fusion of any one of claims 1 to 196, wherein the heavy chain of the trap-antibody fusion or trap-Fab fusion comprises a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:

64.

198. The trap-antibody fusion of any one of claims 1 to 197, wherein the light chain of the trap-antibody fusion or trap-Fab fusion comprises a signal peptide that is SEQ ID NO: 73, a trap that is SEQ ID NO: 71, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

199. The trap-antibody fusion of any one of claims 1 to 198, wherein the light chain of the trap-antibody fusion or trap-Fab fusion comprises a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29.

200. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:73, a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 73, a trap of SEQ ID NO: 71, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 199.

201. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 200.

202. The trap-antibody fusion of any one of claims 1 to 201, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 71, a linker of SEQ ID NO: 25, a VH of SEQ ID NO: 30, and a CH of SEQ ID NO:

64.

203. The trap-antibody fusion of any one of claims 1 to 202, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 71, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

64.

204. The trap-antibody fusion or trap-Fab fusion of any one of claims 1 to 203, wherein the light chain of the trap-antibody fusion or trap-Fab fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 71, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

205. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 71, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 204.

206. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 205.

207. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:73, a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and the light chain of the trap-Fab fusion comprises a signal peptide of SEQ ID NO: 16, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO: 29; The trap-antibody fusion of any one of claims 1 to 206.

208. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and the light chain of the trap-antibody fusion comprises a VL that is SEQ ID NO: 39 and a CL that is SEQ ID NO: 29; The trap-antibody fusion of any one of claims 1 to 207.

209. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 16, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 208.

210. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:64; and the light chain of the trap-antibody fusion comprises a VL that is SEQ ID NO: 39 and a CL that is SEQ ID NO: 29; The trap-antibody fusion of any one of claims 1 to 209.

211. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 71, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 210.

212. the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 64; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 211.

213. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 64; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 73, a trap of SEQ ID NO: 71, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 212.

214. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 28; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 73, a trap of SEQ ID NO: 71, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 213.

215. the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 28; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 214.

216. The trap-antibody fusion of any one of claims 1 to 215, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 71, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

65.

217. The trap-antibody fusion of any one of claims 1 to 216, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 71, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

65.

218. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65; the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 66; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 71, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 217.

219. the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:65; the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 66; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 218.

220. The trap-antibody fusion of any one of claims 1 to 219, wherein the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 72, a trap that is SEQ ID NO: 71, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

66.

221. The trap-antibody fusion of any one of claims 1 to 220, wherein the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO: 71, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

66.

222. the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 65; the heavy chain of the trap-antibody fusion comprises a signal peptide that is SEQ ID NO:72, a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:66; and The light chain of the trap-antibody fusion comprises a signal peptide of SEQ ID NO: 72, a trap of SEQ ID NO: 71, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 221.

223. the heavy chain of the trap-antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 65; the heavy chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, and a CH that is SEQ ID NO:66; and The light chain of the trap-antibody fusion comprises a trap that is SEQ ID NO:71, a linker that is SEQ ID NO:25, a VL that is SEQ ID NO:39, and a CL that is SEQ ID NO:

29. The trap-antibody fusion of any one of claims 1 to 222.

224. The antibody fusion of any one of claims 1 to 223, wherein the heavy chain of the antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VHH that is SEQ ID NO: 74, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

28.

225. The antibody fusion of any one of claims 1 to 224, wherein the heavy chain of the antibody fusion comprises a VHH that is SEQ ID NO: 74, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO:

28.

226. The antibody fusion of any one of claims 1 to 225, wherein the light chain of the antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VHH that is SEQ ID NO: 74, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

227. The antibody fusion of any one of claims 1 to 226, wherein the light chain of the antibody fusion comprises a VHH that is SEQ ID NO: 74, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

228. the heavy chain of the antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VHH that is SEQ ID NO: 74, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 28; and the light chain of the antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VHH that is SEQ ID NO: 74, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29; The antibody fusion of any one of claims 1 to 227.

229. the heavy chain of the antibody fusion comprises a VHH that is SEQ ID NO:74, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, a CH that is SEQ ID NO:28; and the light chain of the antibody fusion comprises a VHH of SEQ ID NO: 74, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO: 29; The antibody fusion of any one of claims 1 to 228.

230. The antibody fusion of any one of claims 1 to 229, wherein the light chain of the antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO:

29.

231. The antibody fusion of any one of claims 1 to 230, wherein the light chain of the antibody fusion comprises a VL that is SEQ ID NO:39 and a CL that is SEQ ID NO:

29.

232. the heavy chain of the antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VHH that is SEQ ID NO: 74, a linker that is SEQ ID NO: 25, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 28; and the light chain of the antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29; 232. The antibody fusion of any one of claims 1 to 231.

233. the heavy chain of the antibody fusion comprises a VHH that is SEQ ID NO:74, a linker that is SEQ ID NO:25, a VH that is SEQ ID NO:30, a CH that is SEQ ID NO:28; and the light chain of the antibody fusion comprises a VL that is SEQ ID NO: 39 and a CL that is SEQ ID NO: 29; The antibody fusion of any one of claims 1 to 232.

234. the heavy chain of the antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 28; and the light chain of the antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VHH that is SEQ ID NO: 74, a linker that is SEQ ID NO: 25, a VL that is SEQ ID NO: 39, and a CL that is SEQ ID NO: 29; The antibody fusion of any one of claims 1 to 233.

235. the heavy chain of the antibody fusion comprises a VH that is SEQ ID NO: 30, a CH that is SEQ ID NO: 28; and the light chain of the antibody fusion comprises a VHH of SEQ ID NO: 74, a linker of SEQ ID NO: 25, a VL of SEQ ID NO: 39, and a CL of SEQ ID NO: 29; 235. The antibody fusion of any one of claims 1 to 234.

236. the heavy chain of the antibody fusion comprises a signal peptide that is SEQ ID NO: 16, a VH that is SEQ ID NO: 30, and a CH that is SEQ ID NO: 28; The antibody fusion of any one of claims 1 to 235.

237. Any of the multivalent trap-antibody fusions of any one of claims 1 to 236; and a polymer covalently attached to said antibody; , a conjugate comprising:

238. A multivalent interleukin (IL) trap-antibody fusion comprising an IL trap and an antibody or fragment thereof, The antibody or fragment thereof a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; a light chain variable region (VL) comprising a VL CDR1, a VL CDR2, and a VL CDR3; the IL trap comprises an IL receptor and an IL accessory protein; the IL trap and antibody are connected in series by a linker; the IL trap-antibody fusion comprises both an IL binding site and an antigen binding site; the IL-binding site and the antigen-binding site are located at separate locations on the trap-antibody fusion; the multivalent IL trap-antibody fusion is conjugated to a polymer; Multivalent IL-Trap-Antibody Fusions.

239. A multivalent interleukin (IL) trap-antibody fusion comprising an IL trap and an antibody, The IL trap is IL receptors, an IL accessory protein; The antibody a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; a light chain variable region (VL) comprising a VL CDR1, a VL CDR2, and a VL CDR3; the interleukin trap and the antibody are connected in series by a linker; the interleukin trap-antibody fusion contains both an IL-binding site and an antigen-binding site; Binding of the IL trap-antibody fusion to IL inhibits IL signaling; the binding of the IL-trap-antibody fusion to an antigen inhibits antigen activity; the multivalent IL trap-antibody fusion is conjugated to a polymer; Multivalent IL-Trap-Antibody Fusions.

240. A multivalent interleukin (IL) trap-Fab fusion comprising an IL trap and an antigen-binding fragment (Fab fragment), the IL trap comprises an IL receptor and an IL accessory protein; the IL trap and the Fab fragment are connected in series by a linker; The IL-trap-Fab fusion contains both an IL-binding site and an antigen-binding site; the IL-binding site and the antigen-binding site are located at separate locations on the trap-Fab fusion; the multivalent IL trap-antibody fusion is conjugated to a polymer; Multivalent IL-Trap-Fab fusions.

241. A multivalent interleukin (IL) trap-Fab fusion comprising an IL trap and an antigen-binding fragment (Fab fragment), the IL trap and the Fab are connected in series by a linker; the multivalent IL-trap-Fab fusion is conjugated to a polymer; Multivalent IL-Trap-Fab fusions.

241. The multivalent interleukin (IL) trap-Fab fusion of any one of claims 1 to 240, comprising: the trap-Fab fusion comprises an IL-1 trap and an anti-IL-6 Fab; the multivalent IL trap-antibody fusion is conjugated to a polymer; Multivalent IL-Trap-Fab fusions.

242. 242. The multivalent interleukin (IL) trap-antibody fusion or multivalent IL trap-Fab fusion of any one of claims 1 to 241, which does not include the transmembrane and / or cellular domain of the IL receptor protein.

243. 243. The multivalent interleukin (IL) trap-antibody fusion or multivalent IL trap-Fab fusion of any one of claims 1 to 242, which does not include the transmembrane and / or cellular domain of the IL receptor accessory protein.

244. The trap-antibody or trap-Fab fusion of any one of claims 1 to 243, which does not contain the transmembrane and / or cellular domain of TNFR1.

245. 245. The trap-antibody or trap-Fab fusion of any one of claims 1 to 244, which does not contain the transmembrane and / or cellular domain of TNFR2.

246. 1. A method of inhibiting cytokine signaling in a subject, comprising: administering a cytokine trap-antibody fusion; The fusion product is Cytokine traps and an antibody; The antibody a heavy chain variable region (VH) comprising three complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3; a light chain variable region (VL) comprising a VL CDR1, a VL CDR2, and a VL CDR3; the IL trap-antibody fusion comprises an IL binding site and an antigen binding site; the cytokine trap-antibody fusion binds to a cytokine, thereby inhibiting cytokine signaling; the cytokine trap-antibody fusion binds to an antigen, thereby inhibiting antigen activity; The method wherein the multivalent cytokine trap-antibody fusion is conjugated to a polymer.

247. The VHH-antibody fusion of any one of claims 1 to 246, which is conjugated to a polymer.

248. The conjugate of any one of claims 1 to 247, wherein the polymer comprises a phosphorylcholine-containing polymer.

249. The polymer comprises zwitterionic monomers, and the zwitterionic monomers are selected from the group consisting of HEMA-phosphorylcholine, PEG, biocompatible fatty acids and their derivatives, hydroxyalkyl starch (HAS), hydroxyethyl starch (HES), polyethylene glycol (PEG), poly(Gly), ｘ -Ser ｙ ) (HAP), hyaluronic acid (HA), heparosan polymer (HEP), Fleximer, dextran, polysialic acid (PSA), Fc domain, transferrin, 25 albumin, elastin-like (ELP) peptide, XT The conjugate of any one of claims 1 to 248, which is selected from the group consisting of an EN polymer, a PAS polymer, a PA polymer, an albumin binding peptide, a CTP peptide, and an FcRn binding peptide.

250. 250. The conjugate of any one of claims 1 to 249, wherein the polymer has a peak molecular weight of 300,000 to 1,750,000 daltons as measured by size exclusion chromatography-multi-angle light scattering (hereinafter "SEC-MALS").

251. 251. The conjugate of any one of claims 1 to 250, wherein the polymer has a peak molecular weight of 500,000 to 1,000,000 daltons as measured by SEC-MALS.

252. 23. The conjugate of claim 22, wherein the polymer has a peak molecular weight of 600,000 to 800,000 daltons as measured by SEC-MALS.

253. The conjugate of any one of claims 1 to 252, wherein the polymer has two or more arms.

254. 254. The conjugate of any one of claims 1-253, wherein the polymer has 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 arms.

255. The conjugate of any one of claims 1 to 254, wherein the polymer has nine arms.

256. The conjugate of any one of claims 1 to 255, wherein the antibody is an IgG.

257. The conjugate of any one of claims 1 to 256, wherein the polymer is covalently attached to a sulfhydryl group derived from a cysteine ​​residue on an IgG heavy chain.

258. The conjugate of any one of claims 1 to 257, wherein the antibody comprises a cysteine ​​residue at position 347 or 443 (EU numbering).

259. 33. The conjugate of claim 32, wherein the polymer is covalently attached to a sulfhydryl group derived from a cysteine ​​residue at position 347 or 443 (EU numbering).

260. 260. The conjugate of any one of claims 1-259, wherein the antibody is further conjugated to a polymer to form a bioconjugate, and the bioconjugate has a molecular weight of about 350,000 daltons to about 1,900,000 daltons.

261. 261. The conjugate of any one of claims 1 to 260, having a polydispersity index (PDI) of 1.5 or less.

262. the polymer has nine arms; the polymer has a molecular weight of about 600,000 Da to about 900,000 Da; A conjugate according to any one of claims 1 to 261.

263. It comprises the following structure: 【Chemistry 1】 During the ceremony, Each heavy chain of an antibody is represented by the letter H, and each light chain of an antibody is represented by the letter L; The polymer is attached to the trap-antibody via the sulfhydryl of C443 (EU numbering), which is shown on one heavy chain; The PC is as follows: 【Chemistry 2】 The wavy line indicates the point of attachment to the rest of the polymer, and X is a) OR, where R is H, methyl, ethyl, propyl, isopropyl, b) H, or c) any halide, including Br; n1, n2, n3, n4, n5, n6, n7, n8, and n9 may be the same or different such that the sum of n1, n2, n3, n4, n5, n6, n6, n7, n8, and n9 is 2500±15%; 263. The conjugate of any one of claims 1 to 262.

264. It comprises the following structure: 【Transformation 3】 During the ceremony, Each heavy chain of an antibody is represented by the letter H, and each light chain of an antibody is represented by the letter L; The polymer is attached to the trap-antibody via the sulfhydryl of C443 (EU numbering), which is shown on one heavy chain; The PC is as follows: 【Chemistry 4】 The wavy line indicates the point of attachment to the rest of the polymer, and X is a) OR, where R is H, methyl, ethyl, propyl, isopropyl, b) H, or c) any halide, including Br; n1, n2, n3, n4, n5, n6, n7, n8, and n9 may be the same or different such that the sum of n1, n2, n3, n4, n5, n6, n6, n7, n8, and n9 is 2500±15%; A conjugate according to any one of claims 1 to 263.

265. A nucleic acid encoding the trap-antibody or trap-Fab fusion of any one of claims 1 to 264.

266. A vector comprising a nucleic acid encoding the trap-antibody or trap-Fab fusion of any one of claims 1 to 265.

267. A cell comprising a vector encoding the trap-antibody or trap-Fab fusion of any one of claims 1 to 266.

268. 268. The trap-antibody fusion of any one of claims 1 to 267, wherein the antibody heavy chain arms are connected by knobs-into-holes.

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