Multi-specific Anti-muscle inhibition drug platform for treating metabolic diseases

Abstract

Provided herein are fusion proteins which can be used as a platform for designing drugs that are multi-specific. The fusion protein can comprise a fragment that binds a muscle-inhibitory factor with different therapeutic peptides coupled to different termini of the fusion protein. The therapeutic peptides can be metabolic peptides. Also provided herein is a method of treating metabolic diseases using the fusion proteins disclosed herein.

Description

Attorney Docket No.: 064630-503001 WOTITLE: MULTI-SPECIFIC ANTI-MUSCLE INHIBITION DRUG PLATFORM FOR TREATING METABOLIC DISEASESCROSS REFERENCE:

[0001] This PCT application claims the benefit to U.S. Provisional Application No. 63 / 736,820, filed December 20, 2024, the content of which is incorporated herein in its entirety by reference.FIELD:

[0002] The present disclosure relates generally to engineered proteins, specifically to engineered multi-specific proteins for treating metabolic diseases.BACKGROUND:

[0003] In certain diseases, multiple biological pathways are implicated and a drug that can provide multiple mechanisms of action (MOA) can be beneficial. For example, multiple tissue and organ involvement and comorbidities are manifested differently in patients with metabolic diseases, such as obesity or muscle wasting. There remains a need for developing drugs that can provide multiple MOAs for treating metabolic diseases.SUMMARY:

[0004] In one aspect, the present disclose provides a fusion protein comprising: (a) an antigen-binding molecule capable of binding at least one muscle-inhibitory factor; (b) a first peptide, the first peptide coupled to a first terminus of the antigen-binding molecule; and (c) a second peptide, the second peptide coupled to a second terminus of the antigen-binding molecule.

[0005] In another aspect, the present disclose provides a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding at least one muscle-inhibitory factor; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the secondAttorney Docket No.: 064630-503001 WO peptide coupled to a terminus of the first region or the second region, wherein the first peptide and the second peptide are coupled to different termini.

[0006] In some embodiments, the first region is N-terminal to the second region. In some embodiments, the first region is C-terminal to the second region.

[0007] In some embodiments, the fusion protein further comprises a third peptide, the third peptide coupled to a third terminus of the antigen-binding molecule or a terminus of the first region or the second region, wherein the first peptide, the second peptide and the third peptide are coupled to different termini.

[0008] In some embodiments, the first peptide, the second peptide, and / or the third peptide comprises a therapeutic peptide. In some embodiments, the therapeutic peptide is a metabolic peptide. In some embodiments, the metabolic peptide comprises a peptide selected from the group consisting of: GLP1 ; GLP2; GIP; GCGP; apelin, Elabela, PYY, LEAP2; amylin; OXM; and analogs or functional variants thereof.

[0009] In some embodiments, each of the termini of the fusion protein is coupled to a peptide.

[0010] In some embodiments, the at least one muscle-inhibitory factor comprises myostatin.

[0011] In another aspect, provided herein is a pharmaceutical composition comprising the fusion protein.

[0012] In other aspects, provided herein are a nucleic acid encoding the fusion protein, a vector comprising said nucleic acid, and a cell comprising said vector.

[0013] In yet another aspect, provided herein are methods of treating diseases in a subject in need thereof, comprising administering the fusion protein or the pharmaceutical composition to the subject.

[0014] Other features and advantages of the present disclosure will become apparent from the following detailed description. The detailed description and the specific examples while indicating embodiments of the disclosure are given by way of illustration only. TheseAttorney Docket No.: 064630-503001 WO detailed description and specific examples are provided for the purposes of explanation, and not limitation, of the disclosure.BRIEF DESCRIPTION OF THE DRAWINGS:

[0015] Fig. 1 depicts a fusion protein comprising two GCGP peptides and two GLP-1 peptides according to some embodiments.

[0016] Fig. 2 depicts a fusion protein comprising two GCGP peptides, two GLP-1 peptides, and two apelin peptides according to some embodiments.

[0017] Fig. 3 depicts a fusion protein comprising two GCGP peptides, two GLP-1 peptides, and two apelin peptides according to some embodiments.

[0018] Fig. 4 depicts a fusion protein comprising two GCGP peptides, two GLP-1 peptides, and two apelin peptides according to some embodiments.

[0019] Fig. 5 depicts a fusion protein comprising two GCGP peptides, two GLP-1 peptides, and two apelin peptides according to some embodiments.

[0020] Fig. 6 depicts a fusion protein comprising two GCGP peptides, two GLP-1 peptides, and two apelin peptides according to some embodiments.

[0021] Fig. 7 depicts a fusion protein comprising two GCGP peptides, two GLP-1 peptides, and two apelin peptides according to some embodiments.

[0022] Fig. 8 depicts a fusion protein comprising two GIP(1 -30) peptides, two GLP-1 peptides, and two apelin peptides according to some embodiments.

[0023] Fig. 9 depicts a fusion protein comprising two G IP( 1 -30) peptides and two GLP- 1 peptides according to some embodiments.

[0024] Fig. 10 depicts a fusion protein comprising two LEAP2 peptides and two GLP- 1 peptides according to some embodiments.

[0025] Fig. 1 1 depicts a fusion protein comprising two GCGP peptides, two GLP-1 peptides, and two apelin peptides according to some embodiments.Attorney Docket No.: 064630-503001 WO

[0026] Fig. 12 depicts a fusion protein comprising two GIP(1 -42) peptides, two GLP-1 peptides, and two apelin peptides according to some embodiments.

[0027] Fig. 13 depicts a fusion protein comprising two apelin peptides according to some embodiments.

[0028] Fig. 14 depicts a fusion protein comprising two apelin peptides according to some embodiments.

[0029] Fig. 15 depicts a fusion protein comprising two apelin peptides according to some embodiments.

[0030] Fig. 16 depicts a fusion protein comprising two apelin peptides according to some embodiments.

[0031] FIG. 17 is a graph showing agonistic activity of fusion proteins of the present disclosure on GLP1 R according to some embodiments.

[0032] FIG. 18A is a graph showing agonistic activity of fusion proteins of the present disclosure on GCGR according to some embodiments.

[0033] FIG. 18B is a graph showing agonistic activity of fusion proteins of the present disclosure on GCGR according to some embodiments.

[0034] FIG. 19A is a graph showing agonistic activity of fusion proteins of the present disclosure on AGTRL1 according to some embodiments.

[0035] FIG. 19B is a graph showing agonistic activity of fusion proteins of the present disclosure on AGTRL1 according to some embodiments.

[0036] FIG. 20 is a graph showing agonistic activity of fusion proteins of the present disclosure on GLP1 R according to some embodiments.DETAILED DESCRIPTION OF THE DISCLOSURE:

[0037] The following is a detailed description provided to aid those skilled in the art in practicing the present disclosure. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The terminology used in the description herein is forAttorney Docket No.: 064630-503001 WO describing particular embodiments only and is not intended to be limiting of the disclosure. All publications, patent applications, patents, figures and other references mentioned herein are expressly incorporated by reference in their entirety.

[0038] All of the features disclosed in this specification may be combined in any combination. Each feature disclosed in this specification may be replaced by an alternative feature serving the same, equivalent, or similar purpose. Thus, unless expressly stated otherwise, each feature disclosed is only an example of a generic series of equivalent or similar features.

[0039] For example, in the following passages, different aspects of the disclosure are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects unless clearly indicated to the contrary.I. Compositions

[0040] Glucagon-like peptide-1 (GLP-1 ) receptor agonists are a class of medications that can regulate blood sugar levels (lowering plasma glucose levels), food intake and energy homeostasis and are used to treat metabolic diseases such as diabetes and obesity. However, these medications are associated with significant muscle loss. Without wishing to be bound by a theory, a GLP-1 receptor agonist that also antagonizes a muscle-inhibitory factor may reduce muscle loss in patients taking GLP-1 receptor agonists.

[0041] Accordingly, in one aspect, provided herein is a fusion protein comprising: (a) an antigen-binding molecule capable of binding at least one muscle-inhibitory factor; (b) a first peptide, the first peptide coupled to a first terminus of the antigen-binding molecule; and (c) a second peptide, the second peptide coupled to a second terminus of the antigen-binding molecule. In one aspect, provided herein is a fusion protein. The fusion protein may comprise an antigen-binding molecule. The antigen-binding molecule may be capable of binding at least one muscle-inhibitory factor. The fusion protein may comprise a first peptide. The first peptide may be coupled to a first terminus of the antigen-binding molecule. The fusion protein may comprise a second peptide. The second peptide may be coupled to a second terminus of the antigen-binding molecule.Attorney Docket No.: 064630-503001 WO

[0042] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding at least one muscle-inhibitory factor; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein the first peptide and the second peptide are coupled to different termini. In another aspect, provided herein is a fusion protein. The fusion protein may comprise a first region. The first region may comprise a first Fab region. The first Fab region may be capable of binding at least one muscle- inhibitory factor. The fusion protein may comprise a second region. The second region may comprise a Fc region. The fusion protein may comprise a first peptide. The first peptide may be coupled to a first terminus of the first region. The first peptide may be coupled to a first terminus of the second region. The fusion protein may comprise a second peptide. The second peptide may be coupled to a first terminus of the first region. The second peptide may be coupled to a first terminus of the second region. The first peptide and the second peptide may be coupled to different termini.Fusion protein

[0043] The fusion protein of the present disclosure can comprise a first region that mediates antigen-binding. The first region can comprise a first Fab region. The first region can further comprise a second Fab region. Either or both of the first Fab region and second Fab region can comprise a light chain and a heavy chain Fab portion. The first Fab region and the second Fab region can bind the same antigen or different antigens. Each of the Fab regions can comprise or consist of an antigen-binding fragment (Fab) of an immunoglobulin.

[0044] In some embodiments, the first Fab region can comprise a light chain. In some embodiments, the first Fab region can comprise a heavy chain Fab portion. The light chain and the heavy chain Fab portion can form one or more disulfide bonds. In some embodiments, the first Fab region can comprise an antigen-binding fragment (Fab) of an immunoglobulin. In some embodiments, the first Fab region can consist of an antigen-binding fragment (Fab) of an immunoglobulin. In some embodiments, the first Fab region can bind the at least one muscle-inhibitory factor. In some embodiments, the first Fab region can specifically bind the at least one muscle-inhibitory factor.Attorney Docket No.: 064630-503001 WO

[0045] In some embodiments, the first region can further comprise a second Fab region. In some embodiments, the second Fab region can comprise a light chain. In some embodiments, the second Fab region can comprise a heavy chain Fab portion. The light chain and the heavy chain Fab portion can form one or more disulfide bonds. In some embodiments, the second Fab region can comprise an antigen-binding fragment (Fab) of an immunoglobulin. In some embodiments, the second Fab region can consist of an antigenbinding fragment (Fab) of an immunoglobulin. In some embodiments, the second Fab region is capable of binding the at least one muscle-inhibitory factor. In some embodiments, the second Fab region can bind the at least one muscle-inhibitory factor. In some embodiments, the second Fab region can specifically bind the at least one muscle-inhibitory factor.

[0046] The fusion protein can comprise a second region. The second region can comprise or consist of a fragment crystallizable (Fc) region of an immunoglobulin. The Fc region can be a Fc region of any immunoglobulin, such as lgG1 , lgG4. The Fc region can comprise a first heavy chain Fc portion. The Fc region can further comprise a second heavy chain Fc portion.

[0047] In some embodiments, the fusion protein comprises a second region. In some embodiments, the second region comprises a Fc region of an immunoglobulin. In some embodiments, the Fc region is a Fc region of IgG 1 . In some embodiments, the Fc region is a Fc region of lgG4. In some embodiments, the Fc region comprises a first Fc portion and a second Fc portion.

[0048] The Fc portions can comprise one or more mutations relative to a native Fc sequence. Such mutations can, for example, improve stability of the fusion protein or half-life of the fusion protein. Such mutations can also reduce or abolish an effector function of the Fc region. (See for example, Xu D, et al, (2000) Cellular Immunology 200: 16-26; Dall'Acqua, W.F., et al. J. Biol. Chem. 281 (2006) 23514-23524).

[0049] In some embodiments, the first heavy chain Fc portion, the second heavy chain Fc portion, or both comprises one or more mutations that improve the stability of the fusion protein and / or a half-life of the fusion protein.Attorney Docket No.: 064630-503001 WO

[0050] In some embodiments, at least one of the Fc portions comprises a mutation corresponding to M252Y in lgG4. In some embodiments, at least one of the Fc portions comprises a mutation corresponding to S254T in lgG4. In some embodiments, at least one of the Fc portions comprises a mutation corresponding to T256E in lgG4. In some embodiments, at least one of the Fc portions comprises one or more mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in lgG4, or any combination thereof.

[0051] In some embodiments, the first heavy chain Fc portion, the second heavy chain Fc portion, or both comprise one or more mutations that reduce or abolish an effector function of the Fc region.

[0052] As used herein, the term “effector function of the Fc region” can comprise a biological function conferred by an immunoglobulin Fc. The biological function can be, for example, binding and / or activating a Fc receptor.

[0053] In some embodiments, at least one of the Fc portions comprises a mutation corresponding to F234A in lgG4. In some embodiments, at least one of the Fc portions comprises a mutation corresponding to L235A in lgG4. In some embodiments, at least one of the Fc portions comprises a mutation corresponding to L234A in lgG1. In some embodiments, at least one of the Fc portions comprises a mutation corresponding to L235A in lgG1. In some embodiments, at least one of the Fc portions comprises one or more mutations corresponding to F234A in lgG4 and / or L235A in lgG4. In some embodiments, at least one of the Fc portions comprises one or more mutations corresponding to L234A in lgG1 and / or L235A in lgG1.

[0054] In some embodiments, at least one of the Fc portions comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to SEQ ID NO: 9 or SEQ ID NO: 10. In some embodiments, at least one of the Fc portions comprises an amino acid sequence of at least 80% sequence identity to SEQ ID NO: 9. In some embodiments, at least one of the Fc portions comprises an amino acid sequence of at least 85% sequence identity to SEQ ID NO: 9. In some embodiments, at least one of the Fc portions comprises an amino acid sequence of at least 90% sequence identity to SEQ ID NO: 9. In some embodiments, at least one of the Fc portions comprises an amino acid sequence of at least 95% sequence identity to SEQ ID NO: 9. In some embodiments, at leastAttorney Docket No.: 064630-503001 WO one of the Fc portions comprises an amino acid sequence of SEQ ID NO: 9. In some embodiments, at least one of the Fc portions comprises an amino acid sequence of at least 80% sequence identity to SEQ ID NO: 10. In some embodiments, t at least one of the Fc portions comprises an amino acid sequence of at least 85% sequence identity to SEQ ID NO: 10. In some embodiments, at least one of the Fc portions comprises an amino acid sequence of at least 90% sequence identity to SEQ ID NO: 10. In some embodiments, at least one of the Fc portions comprises an amino acid sequence of at least 95% sequence identity to SEQ ID NO: 10. In some embodiments, at least one of the Fc portions comprises an amino acid sequence of SEQ ID NO: 10.

[0055] The fusion protein can further comprise a hinge region. The first region and the second region of the fusion protein can be connected through the hinge region. The hinge region can be a hinge region of an immunoglobulin. The immunoglobulin can be of any type or any subclass. In some embodiments, the hinge region is an IgG hinge region. In some embodiments, the IgG hinge region is an lgG1 hinge region. In some embodiments, the IgG hinge region is an lgG4 hinge region.

[0056] The first region and the second region of the fusion protein can be connected without a hinge region. The fusion protein can still comprise a hinge region, for example, to connect at least one peptide to the N-terminal side of the second region.

[0057] In some embodiments, the hinge region is N-terminal to the second region. In some embodiments, the hinge region connects the first region and the second region. In some embodiments, the hinge region connects at least one of the peptides and the second region.

[0058] The hinge region can comprise at least one disulfide bond. The hinge region can comprise two hinge sequences. The two hinge sequences can be coupled through at least one disulfide bond.

[0059] The hinge region can comprise one or more mutations, compared to a native hinge sequence. Such mutations can, for example, eliminate or reduce the effector function of the fusion protein, or promote formation of the fusion protein.Attorney Docket No.: 064630-503001 WO

[0060] In some embodiments, the hinge region comprises one or more mutations that reduce or eliminate an effector function of the Fc region. In some embodiments, at the hinge region comprises one or more mutations that promote formation of the fusion protein.

[0061] In some embodiments, at least one of the hinge sequences comprises a mutation corresponding to S228P in lgG4. In some embodiments, at least one of the hinge sequences comprises a mutation corresponding to F234A in lgG4. In some embodiments, at least one of the hinge sequences comprises a mutation corresponding to L235A in lgG4. In some embodiments, at least one of the hinge sequences comprises one or more mutations corresponding to S228P in lgG4, F234A in lgG4, L235A in lgG4, or any combination thereof.

[0062] In some embodiments, the hinge region comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 17. In some embodiments, the hinge region comprises an amino acid sequence of SEQ ID NO: 17.

[0063] In some embodiments, the hinge region comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 76. In some embodiments, the hinge region comprises an amino acid sequence of SEQ ID NO: 76.

[0064] The first region can be N-terminal to the second region, or it can be C-terminal to the second region. When the first region is N-terminal to the second region, the fusion protein can resemble an immunoglobulin.

[0065] In some embodiments, the heavy chain Fab portion of the first Fab region is N- terminal to the first Fc portion. In some embodiments, the heavy chain Fab portion of the second Fab region is N-terminal to the second Fc portion.

[0066] In some embodiments, the heavy chain Fab portion of the first Fab region is C- terminal to the first Fc portion. In some embodiments, the heavy chain Fab portion of the second Fab region is C-terminal to the second Fc portion.Attorney Docket No.: 064630-503001 WO

[0067] In some embodiments, the N-terminus of the heavy chain Fab portion of the first Fab region is linked to the C-terminus of the first Fc portion via a linker. In some embodiments, the N-terminus of the heavy chain Fab portion of the second Fab region is linked to the C-terminus of the second Fc portion via a linker. In some embodiments, the linker comprises (GGGGS)0-8, (EAAAK)0-8, or combinations thereof.

[0068] The first region and the second region can comprise a plurality of termini. Each of the plurality of termini can be linked to a peptide.

[0069] In some embodiments, the first region comprises two termini. In some embodiments, the first region comprises three termini. In some embodiments, the first region comprises four termini. In some embodiments, none of the plurality of termini of the first region is linked to a peptide. In some embodiments, one of the plurality of termini of the first region is linked to a peptide. In some embodiments, two of the plurality of termini of the first region are linked to a peptide. In some embodiments, three of the plurality of termini of the first region are linked to a peptide. In some embodiments, four of the plurality of termini of the first region are linked to a peptide. In some embodiments, all termini of the first region are linked to a peptide.

[0070] In some embodiments, the second region comprises one terminus. In some embodiments, the second region comprises two termini. In some embodiments, none of the termini of the second region is linked to a peptide. In some embodiments, one of the termini of the second region is linked to a peptide. In some embodiments, two of the termini of the second region are linked to a peptide. In some embodiments, all termini of the second region are linked to a peptide.

[0071] The fusion protein of the present disclosure can comprise an antigen-binding molecule. In some embodiments, the antigen-binding molecule is capable of binding at least one muscle-inhibitory factor. In some embodiments, the antigen-binding molecule binds at least one muscle-inhibitory factor. In some embodiments, the antigen-binding molecule specifically binds at least one muscle-inhibitory factor.

[0072] The antigen-binding molecule can comprise or consist of an antigen-binding fragment. The antigen-binding fragment can be an antigen-binding fragment of anAttorney Docket No.: 064630-503001 WO immunoglobulin. The antigen-binding molecule can comprise or consist of an immunoglobulin.

[0073] In some embodiments, the antigen-binding molecule comprises an antigenbinding fragment. In some embodiments, the antigen-binding molecule comprises an immunoglobulin. In some embodiments, the antigen-binding molecule comprises a heavy chain. The heavy chain can be a heavy chain of an antigen-binding fragment or an immunoglobulin. In some embodiments, the antigen-binding molecule comprises a light chain. The light chain can be a light chain of an antigen-binding fragment or an immunoglobulin. The immunoglobulin can be of any type and any subclass. In some embodiments, the immunoglobulin is an IgG. In some embodiments, the immunoglobulin is an lgG1 or an lgG4.

[0074] The heavy chain of the antigen-binding molecule can comprise a Fc region of an immunoglobulin. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 9. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 10. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 9. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 10.

[0075] The antigen-binding molecule can comprise a first terminus and a second terminus. The antigen-binding molecule can comprise one or more additional termini.

[0076] In some embodiments, the antigen-binding molecule comprises two termini. In some embodiments, the antigen-binding molecule comprises three termini. In some embodiments, the antigen-binding molecule comprises four termini. In some embodiments, the antigen-binding molecule comprises five termini. In some embodiments, the antigenbinding molecule comprises six termini. In some embodiments, the antigen-binding moleculeAttorney Docket No.: 064630-503001 WO comprises more than six termini. In some embodiments, two of the termini of the antigenbinding molecule are linked to a peptide. In some embodiments, three of the termini of the antigen-binding molecule are linked to a peptide. In some embodiments, four of the termini of the antigen-binding molecule are linked to a peptide. In some embodiments, five of the termini of the antigen-binding molecule are linked to a peptide. In some embodiments, six of the termini of the antigen-binding molecule are linked to a peptide. In some embodiments, all of the termini of the antigen-binding molecule are linked to a peptide.

[0077] In some embodiments, the fusion protein comprises eight peptides, wherein each of the eight peptides is coupled to a different terminus.Muscle-inhibitory factor

[0078] The fusion protein disclosed herein is capable of binding at least one muscle- inhibitory factor. Muscle-inhibitory factors can negatively regulate muscle growth and function. Binding of the muscle-inhibitory factor by the fusion protein may reduce activity of the muscle-inhibitory factor and / or reduce inhibition of muscle growth and function. Binding of the muscle-inhibitory factor can reduce an activity of the muscle-inhibitory factor and / or block a function of the muscle-inhibitory factor. Non-limiting examples of muscle-inhibitory factors include myostatin, and activin A.

[0079] In some embodiments, the antigen-binding molecule is capable of binding at least one muscle-inhibitory factor. In some embodiments, the antigen-binding molecule binds at least one muscle-inhibitory factor. In some embodiments, the antigen-binding molecule specifically binds at least one muscle-inhibitory factor.

[0080] In some embodiments, the first Fab region is capable of binding at least one muscle-inhibitory factor. In some embodiments, the first Fab region binds at least one muscle-inhibitory factor. In some embodiments, the first Fab region specifically binds at least one muscle-inhibitory factor. In some embodiments, the second Fab region is capable of binding at least one muscle-inhibitory factor. In some embodiments, the second Fab region binds at least one muscle-inhibitory factor. In some embodiments, the second Fab region specifically binds at least one muscle-inhibitory factor. In some embodiments, at least one of the Fab regions is capable of binding at least one muscle-inhibitory factor. In someAttorney Docket No.: 064630-503001 WO embodiments, at least one of the Fab regions binds at least one muscle-inhibitory factor. In some embodiments, at least one of the Fab regions specifically binds at least one muscle- inhibitory factor.

[0081] In some embodiments, binding of the at least one muscle-inhibitory factor reduces an activity of the at least one muscle-inhibitory factor. In some embodiments, binding of the at least one muscle-inhibitory factor blocks a function of the at least one muscle- inhibitory factor.

[0082] In some embodiments, the at least one muscle-inhibitory factor comprises myostatin. In some embodiments, the at least one muscle-inhibitory factor comprises activin A.

[0083] As used herein, the term “myostatin” refers to the protein MSTN. Other names of the protein include GDF8. The term encompasses homologues and variants thereof.

[0084] The antigen-binding molecule of the fusion protein can comprise an anti- myostatin antibody. The first Fab region, the second Fab region, or both, of the fusion protein can comprise an antigen-binding fragment of an anti-myostatin antibody. Anti-myostatin antibodies include, for example, landogrozumab (LY2495655), Trevogrumab (REGN1033, SAR391786), garetosmab, apitegromab, Domagrozumab (PF-06252616), Stamulumab (MYO-029), SRK-015.

[0085] In some embodiments, the antigen-binding molecule comprises landogrozumab, trevogrumab, garetosmab, apitegromab, domagrozumab, stamulumab, or SRK-015. In some embodiments, the antigen-binding molecule comprises landogrozumab.

[0086] In some embodiments, the first Fab region comprises an antigen-binding fragment of landogrozumab, trevogrumab, garetosmab, apitegromab, domagrozumab, stamulumab, or SRK-015. In some embodiments, the first Fab region comprises an antigenbinding fragment of landogrozumab. In some embodiments, the second Fab region comprises an antigen-binding fragment of landogrozumab, trevogrumab, garetosmab, apitegromab, domagrozumab, stamulumab, or SRK-015. In some embodiments, the second Fab region comprises an antigen-binding fragment of landogrozumab. In some embodiments, at least one of the Fab regions comprises an antigen-binding fragment ofAttorney Docket No.: 064630-503001 WO landogrozumab, trevogrumab, garetosmab, apitegromab, domagrozumab, stamulumab, or SRK-015. In some embodiments, at least one of the Fab regions comprises an antigenbinding fragment of landogrozumab.

[0087] In some embodiments, at least one of the heavy chain Fab portions comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 .

[0088] In some embodiments, at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 2. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 2. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 3. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR2 having an amino acid sequence of SEQ ID NO: 3. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 4. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR3 having an amino acid sequence of SEQ ID NO: 4.

[0089] In some embodiments, at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 2, a CDR2 having an amino acid sequence of SEQ ID NO: 3, and a CDR3 having an amino acid sequence of SEQ ID NO: 4.

[0090] In some embodiments, at least one of the light chains comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%Attorney Docket No.: 064630-503001 WO sequence identity to SEQ ID NO: 5. In some embodiments, at least one of the light chains comprises an amino acid sequence of SEQ ID NO: 5.

[0091] In some embodiments, at least one of the light chains comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 6. In some embodiments, at least one of the light chains comprises a CDR1 having an amino acid sequence of SEQ ID NO: 6. In some embodiments, at least one of the light chains comprises a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 7. In some embodiments, at least one of the light chains comprises a CDR2 having an amino acid sequence of SEQ ID NO: 7. In some embodiments, at least one of the light chains comprises a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 8. In some embodiments, at least one of the light chains comprises a CDR3 having an amino acid sequence of SEQ ID NO: 8.

[0092] In some embodiments, at least one of the light chains comprises a CDR1 having an amino acid sequence of SEQ ID NO: 6, a CDR2 having an amino acid sequence of SEQ ID NO: 7, and a CDR3 having an amino acid sequence of SEQ ID NO: 8.

[0093] In some embodiments, the heavy chain Fab portion of at least one of the Fab regions comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 2; a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 3; a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 4, and the light chain of the at least one of the Fab regions comprises a CDR1 having an amino acid sequence of at leastAttorney Docket No.: 064630-503001 WO80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 6; a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 7; a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 8.

[0094] In some embodiments, the heavy chain Fab portion of at least one of the Fab regions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 2; a CDR2 having an amino acid sequence of SEQ ID NO: 3; a CDR3 having an amino acid sequence of SEQ ID NO: 4, and the light chain of the at least one of the Fab regions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 6; a CDR2 having an amino acid sequence of SEQ ID NO: 7; a CDR3 having an amino acid sequence of SEQ ID NO: 8.

[0095] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 . In some embodiments, the antigenbinding molecule comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 1.

[0096] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 2. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 2. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 3. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR2 having an amino acid sequence of SEQ ID NO: 3. In some embodiments,Attorney Docket No.: 064630-503001 WO the antigen-binding molecule comprises a heavy chain comprising a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 4. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR3 having an amino acid sequence of SEQ ID NO: 4.

[0097] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 2, a CDR2 having an amino acid sequence of SEQ ID NO: 3, and a CDR3 having an amino acid sequence of SEQ ID NO: 4.

[0098] In some embodiments, the antigen-binding molecule comprises a light chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 5. In some embodiments, the antigenbinding molecule comprises a light chain comprising an amino acid sequence of SEQ ID NO: 5.

[0099] In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 6. In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 6. In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 7. In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR2 having an amino acid sequence of SEQ ID NO: 7. In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at leastAttorney Docket No.: 064630-503001 WO99% sequence identity to SEQ ID NO: 8. In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR3 having an amino acid sequence of SEQ ID NO: 8.

[0100] In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 6, a CDR2 having an amino acid sequence of SEQ ID NO: 7, and a CDR3 having an amino acid sequence of SEQ ID NO: 8.

[0101] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 2, a CDR2 having an amino acid sequence of SEQ ID NO: 3, and a CDR3 having an amino acid sequence of SEQ ID NO: 4, and the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 6, a CDR2 having an amino acid sequence of SEQ ID NO: 7, and a CDR3 having an amino acid sequence of SEQ ID NO: 8.

[0102] In some embodiments, at least one of the heavy chain Fab portions comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 96. In some embodiments, at least one of the heavy chain Fab portions comprises an amino acid sequence of SEQ ID NO: 96.

[0103] In some embodiments, at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 97. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 97. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 98. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR2 having an amino acid sequence of SEQ ID NO: 98. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR3 having an amino acid sequence of at least 80%, atAttorney Docket No.: 064630-503001 WO least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 99. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR3 having an amino acid sequence of SEQ ID NO: 99.

[0104] In some embodiments, at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 97, a CDR2 having an amino acid sequence of SEQ ID NO: 98, and a CDR3 having an amino acid sequence of SEQ ID NO: 99.

[0105] In some embodiments, at least one of the light chains comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 108. In some embodiments, at least one of the light chains comprises an amino acid sequence of SEQ ID NO: 100.

[0106] In some embodiments, at least one of the light chains comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 101. In some embodiments, at least one of the light chains comprises a CDR1 having an amino acid sequence of SEQ ID NO: 101 . In some embodiments, at least one of the light chains comprises a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 102. In some embodiments, at least one of the light chains comprises a CDR2 having an amino acid sequence of SEQ ID NO: 102. In some embodiments, at least one of the light chains comprises a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 103. In some embodiments, at least one of the light chains comprises a CDR3 having an amino acid sequence of SEQ ID NO: 103.Attorney Docket No.: 064630-503001 WO

[0107] In some embodiments, at least one of the light chains comprises a CDR1 having an amino acid sequence of SEQ ID NO: 101 , a CDR2 having an amino acid sequence of SEQ ID NO: 102, and a CDR3 having an amino acid sequence of SEQ ID NO: 103.

[0108] In some embodiments, the heavy chain Fab portion of at least one of the Fab regions comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 97; a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 98; a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 99, and the light chain of the at least one of the Fab regions comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 101 ; a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 102; a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 103.

[0109] In some embodiments, the heavy chain Fab portion of at least one of the Fab regions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 97; a CDR2 having an amino acid sequence of SEQ ID NO: 98; a CDR3 having an amino acid sequence of SEQ ID NO: 99, and the light chain of the at least one of the Fab regions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 101 ; a CDR2 having an amino acid sequence of SEQ ID NO: 102; a CDR3 having an amino acid sequence of SEQ ID NO: 103.

[0110] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at leastAttorney Docket No.: 064630-503001 WO98%, or at least 99% sequence identity to SEQ ID NO: 96. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 96.

[0111] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 97. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 97. In some embodiments, the antigenbinding molecule comprises a heavy chain comprising a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 98. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR2 having an amino acid sequence of SEQ ID NO: 98. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 99. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR3 having an amino acid sequence of SEQ ID NO: 99.

[0112] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 97, a CDR2 having an amino acid sequence of SEQ ID NO: 98, and a CDR3 having an amino acid sequence of SEQ ID NO: 99.

[0113] In some embodiments, the antigen-binding molecule comprises a light chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 100. In some embodiments, the antigen-binding molecule comprises a light chain comprising an amino acid sequence of SEQ ID NO: 100.Attorney Docket No.: 064630-503001 WO

[0114] In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 101. In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 101. In some embodiments, the antigenbinding molecule comprises a light chain comprising a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 102. In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR2 having an amino acid sequence of SEQ ID NO: 102. In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 103. In some embodiments, the antigenbinding molecule comprises a light chain comprising a CDR3 having an amino acid sequence of SEQ ID NO: 103.

[0115] In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 101 , a CDR2 having an amino acid sequence of SEQ ID NO: 102, and a CDR3 having an amino acid sequence of SEQ ID NO: 103.

[0116] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 97, a CDR2 having an amino acid sequence of SEQ ID NO: 98, and a CDR3 having an amino acid sequence of SEQ ID NO: 99, and the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 101 , a CDR2 having an amino acid sequence of SEQ ID NO: 102, and a CDR3 having an amino acid sequence of SEQ ID NO: 103.

[0117] In some embodiments, at least one of the heavy chain Fab portions comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at leastAttorney Docket No.: 064630-503001 WO92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 104. In some embodiments, at least one of the heavy chain Fab portions comprises an amino acid sequence of SEQ ID NO: 104.

[0118] In some embodiments, at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 105. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 105. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 106. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR2 having an amino acid sequence of SEQ ID NO: 106. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 107. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR3 having an amino acid sequence of SEQ ID NO: 107.

[0119] In some embodiments, at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 105, a CDR2 having an amino acid sequence of SEQ ID NO: 106, and a CDR3 having an amino acid sequence of SEQ ID NO: 107.

[0120] In some embodiments, at least one of the light chains comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 108. In some embodiments, at least one of the light chains comprises an amino acid sequence of SEQ ID NO: 108.

[0121] In some embodiments, at least one of the light chains comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, atAttorney Docket No.: 064630-503001 WO least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 109. In some embodiments, at least one of the light chains comprises a CDR1 having an amino acid sequence of SEQ ID NO: 109. In some embodiments, at least one of the light chains comprises a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 10. In some embodiments, at least one of the light chains comprises a CDR2 having an amino acid sequence of SEQ ID NO: 1 10. In some embodiments, at least one of the light chains comprises a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 1 1. In some embodiments, at least one of the light chains comprises a CDR3 having an amino acid sequence of SEQ ID NO: 1 11.

[0122] In some embodiments, at least one of the light chains comprises a CDR1 having an amino acid sequence of SEQ ID NO: 109, a CDR2 having an amino acid sequence of SEQ ID NO: 110, and a CDR3 having an amino acid sequence of SEQ ID NO: 11 1.

[0123] In some embodiments, the heavy chain Fab portion of at least one of the Fab regions comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 105; a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 106; a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 107, and the light chain of the at least one of the Fab regions comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 109; a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%,Attorney Docket No.: 064630-503001 WO at least 98%, or at least 99% of SEQ ID NO: 1 10; a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 1 11.

[0124] In some embodiments, the heavy chain Fab portion of at least one of the Fab regions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 105; a CDR2 having an amino acid sequence of SEQ ID NO: 106; a CDR3 having an amino acid sequence of SEQ ID NO: 107, and the light chain of the at least one of the Fab regions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 109; a CDR2 having an amino acid sequence of SEQ ID NO: 110; a CDR3 having an amino acid sequence of SEQ ID NO: 1 11.

[0125] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 104. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 104.

[0126] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 105. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 105. In some embodiments, the antigenbinding molecule comprises a heavy chain comprising a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 106. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR2 having an amino acid sequence of SEQ ID NO: 106. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, atAttorney Docket No.: 064630-503001 WO least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 107. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR3 having an amino acid sequence of SEQ ID NO: 107.

[0127] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 105, a CDR2 having an amino acid sequence of SEQ ID NO: 106, and a CDR3 having an amino acid sequence of SEQ ID NO: 107.

[0128] In some embodiments, the antigen-binding molecule comprises a light chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 108. In some embodiments, the antigen-binding molecule comprises a light chain comprising an amino acid sequence of SEQ ID NO: 108.

[0129] In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 109. In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 109. In some embodiments, the antigenbinding molecule comprises a light chain comprising a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 10. In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR2 having an amino acid sequence of SEQ ID NO: 1 10. In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 11. In some embodiments, the antigenbinding molecule comprises a light chain comprising a CDR3 having an amino acid sequence of SEQ ID NO: 11 1.Attorney Docket No.: 064630-503001 WO

[0130] In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 109, a CDR2 having an amino acid sequence of SEQ ID NO: 1 10, and a CDR3 having an amino acid sequence of SEQ ID NO: 11 1.

[0131] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 105, a CDR2 having an amino acid sequence of SEQ ID NO: 106, and a CDR3 having an amino acid sequence of SEQ ID NO: 107, and the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 109, a CDR2 having an amino acid sequence of SEQ ID NO: 110, and a CDR3 having an amino acid sequence of SEQ ID NO: 1 11.

[0132] In some embodiments, at least one of the heavy chain Fab portions comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 12. In some embodiments, at least one of the heavy chain Fab portions comprises an amino acid sequence of SEQ ID NO: 112.

[0133] In some embodiments, at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 113. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 113. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 14. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR2 having an amino acid sequence of SEQ ID NO: 114. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:Attorney Docket No.: 064630-503001 WO1 15. In some embodiments, at least one of the heavy chain Fab portions comprises a CDR3 having an amino acid sequence of SEQ ID NO: 115.

[0134] In some embodiments, at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 1 13, a CDR2 having an amino acid sequence of SEQ ID NO: 114, and a CDR3 having an amino acid sequence of SEQ ID NO: 1 15.

[0135] In some embodiments, at least one of the light chains comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 16. In some embodiments, at least one of the light chains comprises an amino acid sequence of SEQ ID NO: 1 16.

[0136] In some embodiments, at least one of the light chains comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 17. In some embodiments, at least one of the light chains comprises a CDR1 having an amino acid sequence of SEQ ID NO: 117. In some embodiments, at least one of the light chains comprises a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 18. In some embodiments, at least one of the light chains comprises a CDR2 having an amino acid sequence of SEQ ID NO: 1 18. In some embodiments, at least one of the light chains comprises a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 19. In some embodiments, at least one of the light chains comprises a CDR3 having an amino acid sequence of SEQ ID NO: 1 19.

[0137] In some embodiments, at least one of the light chains comprises a CDR1 having an amino acid sequence of SEQ ID NO: 117, a CDR2 having an amino acid sequence of SEQ ID NO: 118, and a CDR3 having an amino acid sequence of SEQ ID NO: 119.Attorney Docket No.: 064630-503001 WO

[0138] In some embodiments, the heavy chain Fab portion of at least one of the Fab regions comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 1 13; a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 1 14; a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 115, and the light chain of the at least one of the Fab regions comprises a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 1 17; a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 1 18; a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of SEQ ID NO: 1 19.

[0139] In some embodiments, the heavy chain Fab portion of at least one of the Fab regions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 113; a CDR2 having an amino acid sequence of SEQ ID NO: 114; a CDR3 having an amino acid sequence of SEQ ID NO: 1 15, and the light chain of the at least one of the Fab regions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 1 17; a CDR2 having an amino acid sequence of SEQ ID NO: 118; a CDR3 having an amino acid sequence of SEQ ID NO: 1 19.

[0140] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 112. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 112.Attorney Docket No.: 064630-503001 WO

[0141] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 13. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 1 13. In some embodiments, the antigenbinding molecule comprises a heavy chain comprising a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 14. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR2 having an amino acid sequence of SEQ ID NO: 1 14. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 15. In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR3 having an amino acid sequence of SEQ ID NO: 115.

[0142] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 1 13, a CDR2 having an amino acid sequence of SEQ ID NO: 1 14, and a CDR3 having an amino acid sequence of SEQ ID NO: 115.

[0143] In some embodiments, the antigen-binding molecule comprises a light chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 116. In some embodiments, the antigen-binding molecule comprises a light chain comprising an amino acid sequence of SEQ ID NO: 116.

[0144] In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, atAttorney Docket No.: 064630-503001 WO least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 17. In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 117. In some embodiments, the antigenbinding molecule comprises a light chain comprising a CDR2 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 18. In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR2 having an amino acid sequence of SEQ ID NO: 1 18. In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR3 having an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 19. In some embodiments, the antigenbinding molecule comprises a light chain comprising a CDR3 having an amino acid sequence of SEQ ID NO: 119.

[0145] In some embodiments, the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 1 17, a CDR2 having an amino acid sequence of SEQ ID NO: 1 18, and a CDR3 having an amino acid sequence of SEQ ID NO: 119.

[0146] In some embodiments, the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 1 13, a CDR2 having an amino acid sequence of SEQ ID NO: 1 14, and a CDR3 having an amino acid sequence of SEQ ID NO: 115, and the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 1 17, a CDR2 having an amino acid sequence of SEQ ID NO: 118, and a CDR3 having an amino acid sequence of SEQ ID NO: 1 19.Peptides

[0147] In some embodiments, the fusion protein comprises a first peptide and a second peptide, wherein the peptides are to different termini of the fusion protein. In some embodiments, the fusion protein comprises a first peptide, a second peptide and a third peptide, wherein the peptides are coupled to different termini of the fusion protein. In someAttorney Docket No.: 064630-503001 WO embodiments, the fusion protein comprises a first peptide, a second peptide, a third peptide, and a fourth wherein the peptides are coupled to different termini of the fusion protein. In some embodiments, the fusion protein comprises a first peptide, a second peptide, a third peptide, a fourth peptide, and a fifth peptide, wherein the peptides are coupled to different termini of the fusion protein. In some embodiments, the fusion protein comprises a first peptide, a second peptide, a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein the peptides are coupled to different termini of the fusion protein.

[0148] Some peptides may be coupled to any of the termini of the fusion protein. Some peptides may be coupled to selected termini in order to be functional. For example, a specific terminus of a peptide may need to be free in order for the peptide to maintain its activity. In such case, the peptide may be coupled to selected termini of the fusion protein.

[0149] Any suitable peptide can be coupled to a terminus of the fusion protein. The peptide can be a therapeutic peptide. The therapeutic peptide can be a metabolic peptide. Examples of metabolic peptide includes, but are not limited to: GLP-1 , GLP2, GIP, Glucagon (GCGP), apelin, Elabela, LEAP2, amylin, Oxyntomodulin (OXM), and analogs thereof, and functional variants thereof.

[0150] In some embodiments, the first peptide, the second peptide, and / or the third peptide comprises a peptide selected from the group consisting of: GCGP, GLP-1 , GIP, LEAP2, and analogs or functional variants thereof.

[0151] In some embodiments, the first peptide comprises GCGP, or an analog or functional variant thereof. In some embodiments, the first peptide comprises GIP, or an analog or functional variant thereof. In some embodiments, the first peptide comprises LEAP2, or an analog or functional variant thereof. In some embodiments, the second peptide comprises GLP-1 , or an analog or functional variant thereof.

[0152] In some embodiments, the third peptide comprises apelin, or an analog or functional variant thereof. In some embodiments, the third peptide comprises Elabela, or an analog or functional variant thereof.

[0153] As used herein, the term “GLP-1 ” refers to any glucagon-like polypeptide 1. The term includes various forms of GLP-1 , such as GLP-1 (1-37), GLP-1 (1 -36amide), GLP-Attorney Docket No.: 064630-503001 WO1 (7-36amide), and GLP-1 (7-37). GLP-1 is one of the fragments cleaved from proglucagon. For example, it can be amino acid positions 92-128, 98-127, or 98-128 of the human proglucagon (see e.g. UniProt accession no. P01275).

[0154] As used herein, the term “glucagon” or “GCGP” refers to any glucagon polypeptide. GCGP is one of the fragments cleaved from proglucagon. For example, it can be amino acid positions 53-81 of the human proglucagon (see e.g. UniProt accession no. P01275).

[0155] As used herein, the term “GIP” refers to gastric inhibitory polypeptide or glucose-dependent insulinotropic polypeptide. The term includes various forms, such as GIP(1 -42) and GIP(1 -30). GIP can be cleaved from preproGIP. For example, GIP can be amino acids 52-93 of the human preproGIP (see e.g. UniProt accession no. P09681 ).

[0156] As used herein, the term “apelin” refers to a fragment cleaved from preproapelin. For example, the human preproapelin is a 77 amino acid protein. The preproapelin can be cleaved into different fragments, such as apelin-36, apelin-17, and apelin-13. Apelin-36 can refer to amino acids 42-77 of the human apelin protein (see e.g. UniProt accession no. Q9ULZ1 ) or the bovine apelin (see e.g. UniProt accession no. Q9TUI9). Apelin-17 can refer to amino acids 61 -77 of the human apelin protein (see e.g. UniProt accession no. Q9ULZ1 ) or the bovine apelin (see e.g. UniProt accession no. Q9TUI9). Apelin-13 can refer to amino acids 65-77 of the human apelin protein (see e.g. UniProt accession no. Q9ULZ1 ) or the bovine apelin (see e.g. UniProt accession no. Q9TUI9).

[0157] In some embodiments, apelin comprises apelin-36. In some embodiments, apelin comprises apelin-17. In some embodiments, apelin comprises apelin-13.

[0158] As used herein, the term “LEAP2” refers to the mature LEAP2 polypeptide. For example, LEAP2 can refer to amino acids 38-77 of the human liver-expressed antimicrobial peptide 2 prepropeptide (see e.g. UniProt accession no. Q969E1 ) or the bovine liver- expressed antimicrobial peptide 2 prepropeptide (see e.g. UniProt accession no. Q95JC3).

[0159] As used herein, the term “Elabela” refers to a fragment cleaved from the protein Elabela. For example, in human, the protein Elabela is a 54 amino acid protein, and isAttorney Docket No.: 064630-503001 WO encoded by the gene APELA. Other names of the protein Elabela include Apela, ELA and Toddler. The protein Elabela can be cleaved into different fragments, such as Elabela-32, Elabela-21 , and Elabela-1 1 . Elabela-32 can refer to amino acids 23-54 of the human Elabela protein (see e.g. UniProt accession no. P0DMC3) or the mouse Elabela protein (see e.g. UniProt accession no. P0DMC4). Elabela-21 can refer to amino acids 34-54 of the human Elabela protein (see e.g. UniProt accession no. P0DMC3) or the mouse Elabela protein (see e.g. UniProt accession no. P0DMC4). Elabela-1 1 can refer to amino acids 44-54 of the human Elabela protein (see e.g. UniProt accession no. P0DMC3) or the mouse Elabela protein (see e.g. UniProt accession no. P0DMC4).

[0160] In some embodiments, Elabela comprises Elabela-32. In some embodiments, Elabela comprises Elabela-21. In some embodiments, Elabela comprises Elabela-1 1.

[0161] In some embodiments, the GLP-1 comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 1. In some embodiments, the GLP-1 comprises an amino acid sequence of SEQ ID NO: 11.

[0162] In some embodiments, the GCGP comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the GCGP comprises an amino acid sequence of SEQ ID NO: 12.

[0163] In some embodiments, the apelin comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 13, 72 and 73. In some embodiments, the apelin comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to SEQ ID NO: 13. In some embodiments, the apelin comprises an amino acid sequence of SEQ ID NO: 13. In some embodiments, the apelin comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity toAttorney Docket No.: 064630-503001 WOSEQ ID NO: 72. In some embodiments, the apelin comprises an amino acid sequence of SEQ ID NO: 72. In some embodiments, the apelin comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 73. In some embodiments, the apelin comprises an amino acid sequence of SEQ ID NO: 73.

[0164] In some embodiments, the Elabela comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 77, 78, and 79. In some embodiments, the Elabela comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 77. In some embodiments, the Elabela comprises an amino acid sequence of SEQ ID NO: 77. In some embodiments, the Elabela comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 78. In some embodiments, the Elabela comprises an amino acid sequence of SEQ ID NO: 78. In some embodiments, the Elabela comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 79. In some embodiments, the Elabela comprises an amino acid sequence of SEQ ID NO: 79.

[0165] In some embodiments, the GIP comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 14.. In some embodiments, the GIP comprises an amino acid sequence of SEQ ID NO: 14.

[0166] In some embodiments, the GIP comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity toAttorney Docket No.: 064630-503001 WOSEQ ID NO: 15. In some embodiments, the GIP comprises an amino acid sequence of SEQ ID NO: 15.

[0167] In some embodiments, the LEAP2 comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 16. In some embodiments, the LEAP2 comprises an amino acid sequence of SEQ ID NO: 16.

[0168] In some embodiments, the first peptide is coupled to the N-terminus of the light chain of the first Fab region and comprises GCGP, or an analog or functional variant thereof. In some embodiments, the first peptide is coupled to the N-terminus of the light chain of the first Fab region and comprises GIP, or an analog or functional variant thereof. In some embodiments, the first peptide is coupled to the N-terminus of the light chain of the first Fab region and comprises LEAP2, or an analog or functional variant thereof.

[0169] In some embodiments, the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region. In some embodiments, the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region and comprises GLP-1 , or an analog or functional variant thereof.

[0170] In some embodiments, the second peptide is coupled to the N-terminus of the first heavy chain Fc portion. In some embodiments, the second peptide is coupled to the N- terminus of the first heavy chain Fc portion and comprises GLP-1 , or an analog or functional variant thereof.

[0171] In some embodiments, the third peptide is coupled to the N-terminus of the light chain of the second Fab region. In some embodiments, the third peptide is coupled to the N- terminus of the light chain of the second Fab region and comprises GCGP, or an analog or functional variant thereof. In some embodiments, the third peptide is coupled to the N- terminus of the light chain of the second Fab region and comprises GIP, or an analog or functional variant thereof. In some embodiments, the third peptide is coupled to the N- terminus of the light chain of the second Fab region and comprises LEAP2, or an analog or functional variant thereof.Attorney Docket No.: 064630-503001 WO

[0172] In some embodiments, the fourth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region. In some embodiments, the fourth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region and comprises GLP-1 , or an analog or functional variant thereof.

[0173] In some embodiments, the third peptide is coupled to the C-terminus of the first heavy chain Fc portion of the Fc region. In some embodiments, the third peptide is coupled to the C-terminus of the first heavy chain Fc portion of the Fc region and comprises apelin, or an analog or functional variant thereof.

[0174] In some embodiments, the third peptide is coupled to the C-terminus of the light chain of the first Fab region. In some embodiments, the third peptide is coupled to the C- terminus of the light chain of the first Fab region and comprises apelin, or an analog or functional variant thereof. In some embodiments, the third peptide is coupled to the C- terminus of the light chain of the first Fab region and comprises Elabela, or an analog or functional variant thereof.

[0175]

[0176] The peptide can be coupled to a terminus through a linker. In some embodiments, at least one of the peptides is coupled to the first region or the second region through a linker. In some embodiments, the linker comprises (GGGGS)0-8, (EAAAK)0-8, or combinations thereof. In some embodiments, the linker comprises an amino acid sequence of any one of SEQ ID NOs: 18-22. In some embodiments, the linker comprises an amino acid sequence of SEQ ID NO: 18. In some embodiments, the linker comprises an amino acid sequence of SEQ ID NO: 19. In some embodiments, the linker comprises an amino acid sequence of SEQ ID NO: 20. In some embodiments, the linker comprises an amino acid sequence of SEQ ID NO: 21. In some embodiments, the linker comprises an amino acid sequence of SEQ ID NO: 22.

[0177] The same or different linkers can be used at different termini. For example, where a fusion protein comprises peptides at both the first region and the second regions, peptides may be coupled to the first region through a linker different from the linker used to couple peptides to the second region.Attorney Docket No.: 064630-503001 WO

[0178] In some embodiments, the fusion protein comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 80, 84, 88, and 92. In some embodiments, the fusion protein comprises an amino acid sequence of any one of SEQ ID NOs: 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 80, 84, 88, and 92.

[0179] In some embodiments, the fusion protein is encoded by a nucleic acid comprising a nucleotide sequence of at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 25, 29, 33, 37, 41 , 45, 49, 53, 57, 61 , 65, 69, 81 , 85, 89, and 93. In some embodiments, the fusion protein of any of the preceding claims, wherein the fusion protein is encoded by a nucleic acid comprising a nucleotide sequence of any one of SEQ ID NOs: 25, 29, 33, 37, 41 , 45, 49, 53, 57, 61 , 65, 69, 81 , 85, 89, and 93.

[0180] In some embodiments, the fusion protein comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 82, 86, 90, and 94. In some embodiments, the fusion protein comprises an amino acid sequence of any one of SEQ ID NOs: 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 82, 86, 90, and 94.

[0181] In some embodiments, the fusion protein is encoded by a nucleic acid comprising a nucleotide sequence of at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 27, 31 , 35, 39, 43, 47, 51 , 55, 59, 63, 67, 71 , 83, 87, 91 , and 95. In some embodiments, the fusion protein of any of the preceding claims, wherein the fusion protein is encoded by a nucleic acid comprising a nucleotide sequence of any one of SEQ ID NOs: 27, 31 , 35, 39, 43, 47, 51 , 55, 59, 63, 67, 71 , 83, 87, 91 , and 95.Attorney Docket No.: 064630-503001 WOAgonist activities of the fusion protein

[0182] It is demonstrated herein that the fusion proteins disclosed herein can exhibit GLP1 , GCGP, and / or apelin agonist activities. The fusion proteins can have comparable EC50 values as agonists not coupled to the myostatin-binding molecule.

[0183] As used herein, the term “EC50” refers to a concentration of a molecule that induces a half maximal biological response. For example, for a molecule that can activate a receptor, EC50 can be a concentration of the molecule that induces a half maximal activation of the receptor.

[0184] EC50 values can be determined, for example, by cAMP assays, where concentrations of cyclic AMP generated from a biological response (e.g. activation of a receptor) are measured.

[0185] In some embodiments, the fusion protein comprising a GLP-1 peptide has an agonist activity that is the same or substantially the same as an agonist activity of a control.

[0186] The agonist activity may be measured by a EC50 value.

[0187] In some embodiments, the fusion protein comprises a GLP-1 peptide, and the fusion protein comprises a EC50 value of less than about 0.05 nM, less than about 0.045 nM, less than about 0.04 nM, less than about 0.035 nM, less than about 0.03 nM, less than about 0.025 nM, less than about 0.02 nM, less than about 0.019 nM, less than about 0.018 nM, less than about 0.017 nM, less than about 0.016 nM, less than about 0.015 nM, less than about 0.014 nM, less than about 0.013 nM, less than about 0.012 nM, less than about 0.011 nM, less than about 0.01 nM, less than about 0.009 nM, less than about 0.008 nM, less than about 0.007 nM, less than about 0.006 nM, less than about 0.005 nM, less than about 0.004 nM, less than about 0.003 nM, less than about 0.002 nM, or less than about 0.001 nM.

[0188] In some embodiments, the fusion protein comprises a GLP-1 peptide, and the fusion protein comprises a EC50 value that is the same or substantially the same as compared to a control.

[0189] In some embodiments, the fusion protein comprises a GLP-1 peptide, and the fusion protein comprises a EC50 value that is less than about 10%, less than about 20%,Attorney Docket No.: 064630-503001 WO less than about 30%, less than about 40%, less than about 50%, less than about 60%, less than about 70%, less than about 80%, less than about 90%, less than about 100%, less than about 110%, less than about 120%, less than about 130%, less than about 140%, less than about 150%, less than about 160%, less than about 170%, less than about 180%, or less than about 190% of a EC50 value of a control.

[0190] In some embodiments, the fusion protein comprises a GLP-1 peptide, and the fusion protein comprises a EC50 value that is less than about 5-fold, less than about 4-fold, less than about 3-fold, or less than about 2-fold of a EC50 value of a control.

[0191] In some embodiments, the control is a GLP-1 control. In some embodiments, the control is GLP-1 (1 -37).

[0192] The EC50 value may be determined by a cAMP assay. A cAMP assay can comprise measuring intracellular cyclic AMP levels, which can be a measurement of activation of a receptor.

[0193] In some embodiments, the EC50 value is as determined by a cAMP assay. In some embodiments, the cAMP assay comprises a GLP-1 cAMP assay.

[0194] In some embodiments, the fusion protein comprising a GCGP peptide has an agonist activity that is the same or substantially the same as an agonist activity of a control.

[0195] The agonist activity may be measured by a EC50 value.

[0196] In some embodiments, the fusion protein comprises a GCGP peptide, and the fusion protein comprises a EC50 value of less than about 0.5 nM, less than about 0.45 nM, less than about 0.4 nM, less than about 0.35 nM, 0.3 nM, less than about 0.25 nM, less than about 0.2 nM, less than about 0.15 nM, less than about 0.1 nM. less than about 0.09 nM, less than about 0.08 nM, less than about 0.07 nM, less than about 0.06 nM, less than about 0.05 nM, less than about 0.04 nM, less than about 0.03 nM, less than about 0.02 nM, or less than about 0.01 nM.

[0197] In some embodiments, the fusion protein comprises a GCGP peptide, and the fusion protein comprises a EC50 value that is the same or substantially the same as compared to a control.Attorney Docket No.: 064630-503001 WO

[0198] In some embodiments, the fusion protein comprises a GCGP peptide, and the fusion protein comprises a EC50 value that is less than about 10%, less than about 20%, less than about 30%, less than about 40%, less than about 50%, less than about 60%, less than about 70%, less than about 80%, less than about 90%, less than about 100%, less than about 110%, less than about 120%, less than about 130%, less than about 140%, less than about 150%, less than about 160%, less than about 170%, less than about 180%, or less than about 190% of a EC50 value of a control.

[0199] In some embodiments, the fusion protein comprises a GCGP peptide, and the fusion protein comprises a EC50 value that is less than about 5-fold, less than about 4-fold, less than about 3-fold, or less than about 2-fold of a EC50 value of a control.

[0200] In some embodiments, the control is a GCGP control. In some embodiments, the control is glucagon(1 -29).

[0201] The EC50 value may be determined by a cAMP assay. A cAMP assay can comprise measuring intracellular cyclic AMP levels, which can be a measurement of activation of a receptor.

[0202] In some embodiments, the EC50 value is as determined by a cAMP assay. In some embodiments, the cAMP assay comprises a GCGP cAMP assay.

[0203] In some embodiments, the fusion protein comprising an apelin peptide has an agonist activity that is the same or substantially the same as an agonist activity of a control.

[0204] The agonist activity may be measured by a EC50 value.

[0205] In some embodiments, the fusion protein comprises an apelin peptide, and the fusion protein comprises a EC50 value of less than about 900 nM, less than about 800 nM, less than about 700 nM, less than about 600 nM, less than about 500 nM, less than about 400 nM, less than about 300 nM, less than about 200 nM, less than about 100 nM, less than about 90 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 45 nM, less than about 40 nM, less than about 35 nM, less than about 30 nM, less than about 25 nM, less than about 20 nM, less than about 19 nM, less than about 18 nM, less than about 17 nM, less than about 16 nM, less than about 15 nM, less than about 14 nM, less than about 13 nM, less than about 12 nM, less than aboutAttorney Docket No.: 064630-503001 WO1 1 nM, less than about 10 nM, less than about 9 nM, less than about 8 nM, less than about 7 nM, less than about 6 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM,

[0206] In some embodiments, the fusion protein comprises an apelin peptide, and the fusion protein comprises a EC50 value that is the same or substantially the same as compared to a control.

[0207] In some embodiments, the fusion protein comprises an apelin peptide, and the fusion protein comprises a EC50 value that is less than about 10%, less than about 20%, less than about 30%, less than about 40%, less than about 50%, less than about 60%, less than about 70%, less than about 80%, less than about 90%, less than about 100%, less than about 110%, less than about 120%, less than about 130%, less than about 140%, less than about 150%, less than about 160%, less than about 170%, less than about 180%, or less than about 190% of a EC50 value of a control.

[0208] In some embodiments, the fusion protein comprises an apelin peptide, and the fusion protein comprises a EC50 value that is less than about 100-fold, less than about 90- fold, less than about 80-fold, less than about 70-fold, less than about 60-fold, less than about 50-fold, less than about 30-fold, less than about 20-fold, less than about 10-fold, less than about 9-fold, less than about 8-fold, less than about 7-fold, less than about 6-fold, less than about 5-fold, less than about 4-fold, less than about 3-fold, less than about 2-fold of a EC50 value of a control.

[0209] In some embodiments, the control is an apelin control. In some embodiments, the control is apelin 13.

[0210] The EC50 value may be determined by a cAMP assay. A cAMP assay can comprise measuring intracellular cyclic AMP levels, which can be a measurement of activation of a receptor.

[0211] In some embodiments, the EC50 value is as determined by a cAMP assay. In some embodiments, the cAMP assay comprises an apelin cAMP assay.Exemplary fusion proteinsAttorney Docket No.: 064630-503001 WO

[0212] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein each of the first heavy chain Fc portion and the second heavy chain Fc portion comprises mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in lgG4, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds, (2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion, (3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region of the first region; and the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region, (4) the fusion protein further comprises a third peptide and a fourth peptide, wherein the third peptide is coupled to the N-terminus of the light chain of the second Fab region of the first region; and the fourth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region, (5) each of the first peptide, the second peptide, the third peptide, and the fourth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3, and (6) each of the first peptide and the third peptide comprises GCGP or an analog or functional variant thereof; wherein each of the second peptide and the fourth peptide comprises GLP- 1 or an analog or functional variant thereof.

[0213] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprisesAttorney Docket No.: 064630-503001 WO a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein each of the first heavy chain Fc portion and the second heavy chain Fc portion comprises mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in lgG4, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds, (2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion, (3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region, (4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C- terminus of the first heavy chain Fc portion; the fourth peptide is coupled to the N-terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N-terminus of the Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the second heavy chain Fc portion, (5) each of the first peptide, the second peptide, the fourth peptide, and the fifth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3; and each of the third peptide and the sixth peptide is coupled to the second region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3, and, and (6) each of the first peptide and the fourth peptide comprises GCGP or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin or an analog or functional variant thereof.

[0214] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprisesAttorney Docket No.: 064630-503001 WO a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein each of the first heavy chain Fc portion and the second heavy chain Fc portion comprises mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in lgG4, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds, (2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion, (3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the Fab portion of the first Fab region, (4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C-terminus of the first heavy chain Fc portion; the fourth peptide is coupled to the N-terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the second heavy chain Fc portion, (5) each of the first peptide, the second peptide, the fourth peptide, and the fifth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4; and each of the third peptide and the sixth peptide is coupled to the second region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3, and, and (6) each of the first peptide and the fourth peptide comprises GCGP or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin or an analog or functional variant thereof.

[0215] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprisesAttorney Docket No.: 064630-503001 WO a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, (2) the C- terminus of the first heavy chain Fc portion of the second region is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region via a linker having an amino acid sequence of (GGGGS)2, and the C-terminus of the second heavy chain Fc portion is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region via a linker having an amino acid sequence of (GGGGS)2, (3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the first heavy chain Fc portion via a first hinge sequence, (4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C-terminus of the light chain of the first Fab region; the fourth peptide is coupled to the N-terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N-terminus of the second heavy chain Fc portion via a second hinge sequence; and the sixth peptide is coupled to the C-terminus of the light chain, (5) the first hinge sequences and the second hinge sequences comprise mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4, and are linked via at least two disulfide bonds, (6) each of the first peptide, the third peptide, the fourth peptide, and the sixth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4; the second peptide is coupled to the first hinge sequence via a linker, wherein the linker has an amino acid sequence of (GGGGS)3; and the fifth peptide is coupled to the second hinge sequence via a linker, wherein the linker has an amino acid sequence of (GGGGS)3, and (7) each of the first peptide and the fourth peptide comprises GCGP or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin or an analog or functional variant thereof.

[0216] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprisesAttorney Docket No.: 064630-503001 WO a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds, (2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion, (3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region ion, (4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C-terminus of the light chain of the first Fab region; the fourth peptide is coupled to the N- terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N- terminus of the heavy chain Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the light chain of the second Fab region, (5) each of the first peptide, the second peptide, the fourth peptide, and the fifth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3; and each of the third peptide and the sixth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4, and (6) each of the first peptide and the fourth peptide comprises GCGP or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin or an analog or functional variant thereof.

[0217] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc regionAttorney Docket No.: 064630-503001 WO comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds, (2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion, (3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region; (4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C- terminus of the light chain of the first Fab region; the fourth peptide is coupled to the N- terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N- terminus of the Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the light chain of the second Fab region of, (5) each of the first peptide, the second peptide, the fourth peptide, and the fifth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3; and each of the third peptide and the sixth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)5, and (6) each of the first peptide and the fourth peptide comprises GCGP or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin or an analog or functional variant thereof.

[0218] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a)Attorney Docket No.: 064630-503001 WO mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds, (2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion, (3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region; (4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C- terminus of the light chain of the first Fab region; the fourth peptide is coupled to the N- terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N- terminus of the heavy chain Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the light chain of the second Fab region, (5) each of the first peptide, the second peptide, the fourth peptide, and the fifth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3; and each of the third peptide and the sixth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)6, and (6) each of the first peptide and the fourth peptide comprises GCGP or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin or an analog or functional variant thereof.

[0219] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds, (2) the C-terminus of the heavy chain Fab portion of the first Fab region isAttorney Docket No.: 064630-503001 WO coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion, (3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the Fab portion of the first Fab region, (4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C-terminus of the first heavy chain Fc portion; the fourth peptide is coupled to the N-terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the second heavy chain Fc portion, (5) each of the first peptide, the second peptide, the fourth peptide, and the fifth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4; and each of the third peptide and the sixth peptide is coupled to the second region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3, and, and (6) each of the first peptide and the fourth peptide comprises GIP or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin or an analog or functional variant thereof.

[0220] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds, (2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavyAttorney Docket No.: 064630-503001 WO chain Fc portion, (3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the Fab portion of the first Fab region, (4) the fusion protein further comprises a third peptide and a fourth peptide, wherein: the third peptide is coupled to the N-terminus of the light chain of the second Fab region; and the fourth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region, (5) each of the first peptide, the second peptide, the third peptide, and the fourth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4, and (6) each of the first peptide and the third peptide comprises GIP or an analog or functional variant thereof; wherein each of the second peptide and the fourth peptide comprises GLP-1 or an analog or functional variant thereof.

[0221] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds, (2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion, (3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the Fab portion of the first Fab region, (4) the fusion protein further comprises a third peptide and a fourth peptide, wherein: the third peptide is coupled to the N-terminus of the light chain of the second Fab region; and the fourth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region, (5) each of the first peptide, the second peptide, the third peptide, and the fourth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3, and (6) each of the first peptide and the third peptideAttorney Docket No.: 064630-503001 WO comprises LEAP2 or an analog or functional variant thereof; wherein each of the second peptide and the fourth peptide comprises GLP-1 or an analog or functional variant thereof.

[0222] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds, (2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion, (3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region of; and the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region, (4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C- terminus of the light chain of the first Fab region; the fourth peptide is coupled to the N- terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N- terminus of the heavy chain Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the light chain of the second Fab region, (5) each of the first peptide, the second peptide, the fourth peptide, and the fifth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3; and each of the third peptide and the sixth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3, and (6) each of the first peptide and the fourth peptide comprises GCGP or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin or an analog or functional variant thereof.Attorney Docket No.: 064630-503001 WO

[0223] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds, (2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion, (3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region; (4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C- terminus of the light chain of the first Fab region; the fourth peptide is coupled to the N- terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N- terminus of the heavy chain Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the light chain of the second Fab region, (5) each of the first peptide, the second peptide, the fourth peptide, and the fifth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3; and each of the third peptide and the sixth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3, and (6) each of the first peptide and the fourth peptide comprises GIP or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin or an analog or functional variant thereof.

[0224] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second regionAttorney Docket No.: 064630-503001 WO comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein each of the first heavy chain Fc portion and the second heavy chain Fc portion comprises mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in lgG4, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds, (2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C- terminus of the heavy chain Fab portion of the second Fab region is coupled to the N- terminus of the second heavy chain Fc portion, (3) the first peptide is coupled to the C- terminus of the first heavy chain Fc portion; and the second peptide is coupled to the C- terminus of the second heavy chain Fc portion, (4) each of the first peptide and the second peptide is coupled to the second region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4-6, and (5)each of the first peptide and the second peptide comprises apelin, or an analog or functional variant thereof.

[0225] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein each of the first heavy chain Fc portion and the second heavy chain Fc portion comprises mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in lgG4, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) twoAttorney Docket No.: 064630-503001 WO disulfide bonds, (2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion, (3) the first peptide is coupled to the C-terminus of the light chain of the first Fab region; and the second peptide is coupled to the C-terminus of the light chain of the second Fab region, (4) each of the first peptide and the second peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4-6, and (5) each of the first peptide and the second peptide comprises apelin, or an analog or functional variant thereof.

[0226] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein each of the first heavy chain Fc portion and the second heavy chain Fc portion comprises mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in lgG4, (2) the fusion protein further comprises a hinge region at the N-terminus of the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds, (3) the N-terminus of the heavy chain Fab portion of the first Fab region is coupled to the C-terminus of the first heavy chain Fc portion, and the N- terminus of the heavy chain Fab portion of the second Fab region is coupled to the C- terminus of the second heavy chain Fc portion, (4) the first peptide is coupled to the C- terminus of the light chain of the first Fab region; and the second peptide is coupled to the C-terminus of the light chain of the second Fab region, (5) each of the first peptide and the second peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4-6, and (6) each of the first peptide and the second peptide comprises apelin, or an analog or functional variant thereof.Attorney Docket No.: 064630-503001 WO

[0227] In another aspect, provided herein is a fusion protein comprising: (a) a first region comprising a first Fab region capable of binding myostatin; (b) a second region comprising a Fc region; (c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and (d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein (1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein each of the first heavy chain Fc portion and the second heavy chain Fc portion comprises mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in lgG4, (2) the fusion protein further comprises a hinge region at the N-terminus of the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds, (3) the N-terminus of the heavy chain Fab portion of the first Fab region is coupled to the C-terminus of the first heavy chain Fc portion, and the N- terminus of the heavy chain Fab portion of the second Fab region is coupled to the C- terminus of the second heavy chain Fc portion, (4) the first peptide is coupled to the C- terminus of the first heavy chain Fc portion; and the second peptide is coupled to the C- terminus of the second heavy chain Fc portion, (5) each of the first peptide and the second peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4-6, and (6) each of the first peptide and the second peptide comprises apelin, or an analog or functional variant thereof.II. Nucleic acids, vectors, compositions, and cells

[0228] In another aspect, provided herein is a nucleic acid comprising nucleic acid sequences encoding the fusion protein, or part of the fusion protein disclosed herein.

[0229] In some embodiments, the nucleic acid comprises a nucleotide sequence of at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 25, 29, 33, 37, 41 , 45, 49, 53, 57, 61 , 65, 69, 81 , 85, 89, and 93. In some embodiments, the nucleic acid comprises a nucleotideAttorney Docket No.: 064630-503001 WO sequence of any one of SEQ ID NOs: 25, 29, 33, 37, 41 , 45, 49, 53, 57, 61 , 65, 69, 81 , 85, 89, and 93.

[0230] In some embodiments, the nucleic acid comprises a nucleotide sequence of at least 70%, at least 75%, at least 80%, at least 85, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 27, 31 , 35, 39, 43, 47, 51 , 55, 59, 63, 67, 71 , 83, 87, 91 , and 95. In some embodiments, the nucleic acid comprises a nucleotide sequence of any one of SEQ ID NOs: 27, 31 , 35, 39, 43, 47, 51 , 55, 59, 63, 67, 71 , 83, 87, 91 , and 95.

[0231] Also provided herein is a vector comprising the nucleic acid. The vector can comprise one or more of the nucleic acid sequences. The vector can be an expression vector. The vector can comprise an expression cassette.

[0232] In another aspect, provided herein is a cell comprising the vector. The cell can be used to express the fusion protein disclosed herein. The cell can be any suitable host cell, including prokaryotic and eukaryotic host cells.

[0233] In a further aspect, provided herein is a pharmaceutical composition comprising the fusion protein disclosed herein. The composition can further comprise a pharmaceutically acceptable carrier. A pharmaceutically acceptable carrier can be any additive, adjuvant, diluent, or other component that is included in a formulation of the fusion protein for administration to a subject, that does not abrogate the desired activity or property of the fusion protein.III. Methods

[0234] In a further aspect, provided herein is a method of treating a disease in a subject in need thereof, comprising administering the fusion protein of the present disclosure to the subject.

[0235] In some embodiments, the disease comprises a metabolic disease.

[0236] In some embodiments, the disease comprises a muscle wasting disease.Attorney Docket No.: 064630-503001 WO

[0237] In some embodiments, the metabolic disease is obesity, Type 1 diabetes, Type 2 diabetes, metabolic syndrome, insulin resistance, obesity-related heart failure, obesity- associated pulmonary arterial hypertension, fatty liver disease, MASH, or MASLD.

[0238] In some embodiments, the administration can result in lowered plasma glucose, reduced gastric and / or intestinal mobility, reduced gastric and / or intestinal emptying, reduced food intake, body weight loss or any combination thereof in the subject, compared to a control subject. A control subject can be, for example, a subject not administered the fusion protein.

[0239] In some embodiments, the administration results in positive inotropic effects, myocardial protection, lowered systolic blood pressure, cardiac improvement, renoprotection, reduced inflammation, muscle regeneration, growth and adaptation, or any combination thereof in the subject, compared to a control subject. A control subject can be, for example, a subject not administered the fusion protein.

[0240] In some embodiments, the administration results in muscle preservation in the subject. In some embodiments, the administration results in loss of fat mass in the subject.

[0241] In some embodiments, the administration results in reduced muscle loss in the subject as compared to a control subject.

[0242] In some embodiments, the reduced muscle loss comprises less than about 90%, less than about 80%, less than about 70%, less than about 60%, less than about 50%, or less than over about 50% of a muscle loss level in a control subject about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 9 months, about 12 months, or after 12 months after the administration. The control subject can, for example, be a subject administered a GLP-1 receptor agonist without a muscle- inhibitory factor. Non-limiting examples of GLP-1 receptor agonists without a muscle- inhibitory factor include semaglutide, liraglutide, dulaglutide, and exenatide.

[0243] In some embodiments, the reduced muscle loss comprises less than about 90% of a muscle loss level in a control subject about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 9 months, about 12 months, or after 12 months after the administration. In some embodiments, the reduced muscle lossAttorney Docket No.: 064630-503001 WO comprises less than about 80% of a muscle loss level in a control subject about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 9 months, about 12 months, or after 12 months after the administration. In some embodiments, the reduced muscle loss comprises less than about 70% of a muscle loss level in a control subject about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 9 months, about 12 months, or after 12 months after the administration. In some embodiments, the reduced muscle loss comprises less than about 60% of a muscle loss level in a control subject about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 9 months, about 12 months, or after 12 months after the administration. In some embodiments, the reduced muscle loss comprises less than about 50% of a muscle loss level in a control subject about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 9 months, about 12 months, or after 12 months after the administration. In some embodiments, the reduced muscle loss comprises less than over about 50% of a muscle loss level in a control subject about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 9 months, about 12 months, or after 12 months after the administration.IV. Definitions

[0244] Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by those of ordinary skill in the art to which the disclosure pertains.

[0245] As used herein, the singular forms “a,” “an,” and “the” include plural references, unless indicated otherwise. For example, a reference to “a molecule” can be a reference to more than one molecule.

[0246] The term “or” is generally used to mean “and / or”, unless it is indicated explicitly to refer to alternatives only. The phrase “and / or” means “either or both” of the elements so conjoined. These terms can convey that any combination is specifically contemplated. It should also be noted that the term “or” is generally employed in its sense including “and / or” unless the content clearly dictates otherwise. These terms can convey that any combination is specifically contemplated. Solely for illustrative purposes, the expression “A, B, and / or C”Attorney Docket No.: 064630-503001 WO can mean A individually; B individually; C individually; A and B; B and C; A and C; and A, B, and C.

[0247] The term “comprise”, “comprising”, or the like is open-ended and means additional elements or components other than those recited may be present. Other terms such as “include”, “contain”, “have” and the like have similar meaning.

[0248] The term “consist of”, “consisting of” or the like is closed-ended and means no additional component is present.

[0249] Further, terms of degree such as "substantially", "about" and "approximately" as used herein mean within an acceptable error range for the particular value, or a reasonable amount of deviation of the modified term, as determined by one of ordinary skill in the art. These terms of degree should be construed as including a deviation of at least ±5% of the modified term if this deviation would not negate the meaning of the word it modifies.

[0250] More specifically, the term “about” or “approximately” when used in reference to a particular recited value, means there can be an acceptable variation range, as determined by one of ordinary skill in the art to which this disclosure pertains. The term can mean ±10%, ±5%, ±2%, or ±1 %. Where a particular value is recited, it can be understood that the value is modified by the term “about” or “approximately”, unless indicated otherwise. The recitation of numerical ranges includes all numbers and fractions within that range (e.g. 1 to 5 includes 1 , 1.5, 2, 2.75, 3, 3.90, 4, and 5).

[0251] The term “peptide” as used herein refer to a polymer of at least two amino acids. The amino acids may be natural amino acids, or analogues or derivatives thereof. The term encompasses modifications, such as modifications to the backbone and modifications to side chains.

[0252] The term “antigen-binding fragment” means any polypeptide that can bind specifically to an epitope of an antigen. Examples of antigen-binding fragments include but are not limited to Fab (fragment antigen binding), F(ab’), F(ab’)2, Fd fragments, Fv fragments, scFv (single chain fragment variable), single domain antibodies, Fc (fragment crystallizable).Attorney Docket No.: 064630-503001 WO

[0253] The term “immunoglobulin” or “Ig” refers to a molecule comprising at least one heavy chain polypeptide and at least one light chain polypeptide and is capable of specific binding of a target through at least one antigen-binding site. Different types of immunoglobulins can have different numbers of heavy and light chains. Each of the heavy chain and the light chain can comprise a variable region (VH) and a constant region. Each variable region typically includes three complementarity determining regions (“CDR”), which are regions of hypervariability. A framework region “FR” can be present around each CDR. In such case, a representation of a variable region can be, from the N-terminus to the C- terminus: FR1 -CDR1 -FR2-CDR2-FR3-CDR3-FR4. The constant region of the heavy chain can comprise multiple constant domains. For instant, in the case of an IgG, a typical heavy chain constant region can comprise 3 constant domains (CH1 , CH2, CH3). A typical light chain constant region of an Ig can comprise 1 constant domain (CL1 ). The heavy chain and the light chain can be coupled non-covalently through one or more disulfide bonds, such as a disulfide bond between CL1 and CH1. The structure of an immunoglobulin can be divided into a Fab region and a Fc region, where the Fab region includes the antigen-biding site and a constant region. The Fc region can interact with a Fc receptor on, for example, an effector cell. Binding of the Fc region with the Fc receptor can trigger a signaling pathway of the effector cell. The constant region of the Fab region can include the constant domain of the light chain and one of the constant domains of the heavy chain (e.g. CH1 ), and the Fc region can include the remaining constant domains of the heavy chain (e.g. CH2 and CH3 for an IgG). The Fab region and the Fc region are typically connected by a hinge region, comprising a hinge sequence of the heavy chain polypeptide.

[0254] Various types of immunoglobulins are known, including IgG, IgA, IgD, Ig E, and IgM. Some types can include subclasses. For example, IgG includes at least lgG1 , lgG2, lgG3, and lgG4.

[0255] The term “immunoglobulin” and the term “antibody” are used interchangeably herein.

[0256] The term “variable region” refers to a region that mediates antigen binding. The variable region can comprise a variable region of a light chain and a variable region of a heavy chain.Attorney Docket No.: 064630-503001 WO

[0257] The term “variant” in the context of a protein or polypeptide means a protein or polypeptide that share a certain percentage amino acid sequence identity with a reference upon alignment of the amino acid sequences. A variant may have the same or a different number of amino acids as the reference.

[0258] The term “functional fragment” in the context of a protein or polypeptide means a fragment that is capable of having one or more activities of a reference protein or polypeptide.

[0259] The term “Fab region” in the context of the fusion protein of the present disclosure refers to a region of the fusion protein that can bind an antigen. The Fab region of the fusion protein can comprise a light chain and a portion of a heavy chain that comprises a variable region. The Fab region can comprise a fragment antigen-binding (Fab) region of an immunoglobulin.

[0260] The term “light chain” in the context of the fusion protein of the present disclosure refers to a polypeptide comprising a variable region that together with the variable region of the heavy chain Fab region, form the antigen-binding site of the fusion protein. In some embodiments, the light chain of the fusion protein comprises a light chain polypeptide of an immunoglobulin. The light chain polypeptide can be a native light chain polypeptide, or a variant thereof.

[0261] The term “heavy chain Fab portion” in the context of the fusion protein of the present disclosure refers to a part of a heavy chain that comprises a variable domain. The heavy chain Fab portion can further comprise a constant domain. In some embodiments, the heavy chain Fab portion comprises a Fab sequence of a heavy chain polypeptide. The heavy chain polypeptide can be a native heavy chain polypeptide, or a variant thereof.

[0262] The term “heavy chain Fc portion” in the context of the fusion protein of the present disclosure refers to a part of a heavy chain that comprises a Fc region. In some embodiments, the heavy chain Fc portion comprises a Fc sequence of a heavy chain polypeptide. The heavy chain polypeptide can be a native heavy chain polypeptide, or a variant thereof.Attorney Docket No.: 064630-503001 WO

[0263] As used herein, the term “myostatin” refers to the protein MSTN. Other names of the protein include GDF8. The term encompasses homologues and variants thereof.

[0264] The term “nucleic acid” or “nucleic acid molecule” refers to covalently linked sequence of nucleotides, such as ribonucleotides and deoxyribonucleotides, and encompass analogs and derivatives of natural nucleotides and modifications. A nucleic acid molecule may be formed by a single type of nucleotides (e.g. DNA or RNA), or it may be a hybrid of different nucleotides, for example, a DNA / RNA hybrid. A nucleic acid molecule may be single- stranded, double-stranded, or partially double-stranded. For example, a nucleic acid molecule may have a stem-loop structure, where the stem portion is double-stranded and the loop portion is single-stranded. A nucleic acid may be in different conformations, such as linear or circular.

[0265] The term “vector” means any vehicle capable of transferring genetic material into a cell.

[0266] The term "expression cassette", as used herein, refers to a DNA molecule comprising a nucleotide sequence that is expressed (transcribed) upon transfer into a cell, tissue or organ. Typically, an expression cassette comprises at least one gene (which may include a promoter, an open reading frame, and a termination signal).

[0267] The term “expression vector” means a vector capable of expressing the genetic material transferred into the cell. Expressing the genetic material can comprise transcribing into a messenger RNA, and / or translating into a polypeptide.

[0268] The term “operably linked” means that two components are coupled in a manner so that one component affects the function of the other component. For example, a sequence can be operably linked to a regulatory element such that the regulatory element can regulate the expression of the sequence.

[0269] The term “regulatory element” refers to a sequence capable to controlling expression of a nucleic acid and can include controlling at the level of transcription and translation [and replication]. Examples of regulatory elements can include, without limitation, promoters, enhancers, terminators, transcription termination signals, such as polyadenylation (poly-A) signals, 5’-UTR, 3’-UTR, IRES (internal ribosomal entry sites), etc.Attorney Docket No.: 064630-503001 WOA regulatory element can control expression in a temporally and / or spatially regulated manner. A regulatory element can direct tissue- or cell-specific expression, for example, in neurons, specific types of neurons, etc. It can also drive expression in specific cell cycle stage, specific developmental stage, and / or other temporal manner. A regulatory element may direct constitutive expression of a target gene. A regulatory element may drive the expression of a target gene in an inducible manner.

[0270] The term “treat”, “treating” or similar terms means achieving a beneficial or desired result, which can comprise (1 ) diminishing the extent of or reversing a disease or condition; (2) slowing, delaying, or arresting the progression of a disease or condition; (3) ameliorating or alleviating one or more symptoms of a disease or condition.

[0271] The term “administering”, “administer”, “administration” or the like encompasses external and internal administration. Internal administration can refer to, for example, where a molecule is generated inside the subject’s body. For example, administering a polypeptide encompasses administering a nucleic acid encoding the polypeptide, and the polypeptide is expressed from the nucleic acid inside a cell of the subject.

[0272] The term “pharmaceutically acceptable” means suitable to be administered to a subject, having regard to potential risks and benefits and within the scope of sound medical judgement.

[0273] The term "sequence identity" as used herein refers to the percentage of sequence identity between two amino acid sequences or two nucleic acid sequences. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences. The sequences can be of the same length or of different lengths. Gaps may be artificially introduced into the sequence to attain proper alignment. Once the optimal alignment has been set up, the degree of identity is established by recording all of the positions in which the amino acids of both sequences are identical, relative to the total number of positions. As would be understood by a person skilled in the art, the determination of percent identity between two sequences can also be accomplished using a mathematical algorithm. Various sequence analysis software and online programs can be used to determine sequence identity, such as BLAST.Attorney Docket No.: 064630-503001 WO

[0274] The definitions and embodiments described in particular sections are intended to be applicable to other embodiments herein described for which they are suitable as would be understood by a person skilled in the art.

[0275] Various features and embodiments of the present invention will now be described by way of non-limiting examples.EXAMPLESExample 1Expression and purification of fusion proteins

[0276] I. Method

[0277] Preparation of the expression constructs: Based on the designed amino acid sequences, DNA sequences were synthesized with signal sequence after codon optimization. After verification of the constructs by sequencing, a large-scale plasmid preparation was performed to obtain sufficient DNA for transfection.

[0278] WuXianTM Transient Expression Method: CHO K1 host cells were passaged every 3 or 4 days to obtain a sufficient number of cells. On the day of transfection, host cells were diluted to an appropriate density with the transfection media which were placed in a water-bath with 36.5°C in advance. Then the cells were put into a 100mL liquid storage tank for future use. The plasmid with heavy chain coding and the plasmid with light chain coding of the fusion protein were mixed in tubes. The plasmid ratios of all molecules were 1 :1 .Transfection reagents and media were poured into 100mL tanks respectively. The plasmid and transfection reagents were added into cells of 96 deep well plate (DWP) by workstation. The 96 DWP was put back to the shaker with 36.5°C. 24 hours after transfection, the temperature was shifted to 33°C. On day 4 after transfection, feeding media was added into the cells. On day 7 after transfection, cell culture was harvested for purification.

[0279] Purification: The supernatants from the cell cultures were harvested by centrifugation at 1000 x g for 10 min. The supernatant was transferred to a deep well plate by workstation and was purified by Protein A resin. Samples from Protein A resin eluate were immediately neutralized to pH 5.5 . After the affinity chromatography purification step, samples were transferred to desalting plate, and were formulated in PBS by centrifugation atAttorney Docket No.: 064630-503001 WO1000g, 2 min. Then SEC-HPLC and Caliper SDS were performed to examine the purity and aggregation properties of the purified antibody fusion proteins.

[0280] II. Analysis and characterization: the affinity-purified fusion proteins were then placed into a storage buffer (0.1 M Hac, 130 mM Tris, pH 5.5) and dialyzed into PBS (pH 7.4) for further analysis and characterization. The purity and aggregation property of the fusion proteins were assessed by Caliper-SDS PAGE under both non-reduced and reduced conditions and SEC_HPLC. Results are shown in Table 1.Table 1. Expression and characterizationExample 2In vitro assays

[0281] In vitro biological activities of the GLP1 , glucagon and apelin receptor agonists were assessed using cAMP assay based on HTRF technology.

[0282] Methods:Attorney Docket No.: 064630-503001 WO

[0283] Target cells were harvested by centrifugation and resuspended with corresponding complete culture medium. The target cell suspension (5E5 cells / mL, 5uL / well) was transferred to a 384-well assay plate. 2x working solutions (containing 1 nM IBMX) of test or reference items with corresponding complete culture medium were prepared. 2x working solutions of test and reference items (5 uL / well) were added to the corresponding wells of the assay plate containing target cells (with serially diluted reference and test items) and incubate at 37eC for 30 minutes. The cAMP-Gs Dynamic kit solution (10 uL / well) prepared according to the instructions was added to the corresponding wells of the assay plate and incubated at room temperature in the dark for 1 hour. HTRF signals were read using a microplate reader. For data analysis, raw data and readings were exported from PHERAstar FSX system and analyzed using Microsoft office Excel 2021 and GraphPad Prism 6. and GraphPad Prism 6. In GraphPad Prism 6 software, relative EC50 value was obtained using Four Parameter Logistic regression model where the HTRF Ratio (Signals nm / Signal620mn x 10000) was against the concentration of test items:Y = bottom + (Top - Bottom) / (1 + 10A((LogEC50-X) x HillSlope)) where X = Log (Concentration of test items), Y = HTRF Ratio

[0284] (a) GLP1R agonist assay: cAMP accumulation assays were performed using the target expressing cells, CHO-K1 / GLPIR / Ga15. Results are shown in Table 2 and Table 5. The positive control used in the GLP1 R agonist assay was GLP1 (7-37).

[0285] Result of cAMP assay for positive control and test samples targeting GLPIR is shown in FIGs. 17 and 20. CHO-K1 / GLPIR / Ga15 cells were incubated at 37 °C for 30 minutes with serially diluted positive control (GLP-1 (7-37)) and test samples (1 1 and 13). Each data point represents mean * SEM (n =3).

[0286] In the experiment of FIG. 17, the positive control, GLP-1 (7-37), demonstrated significant agonistic activity on CHO-K1 / GLP1 R / Ga15 cells in a dose-dependent manner. The test samples (11 and 13), demonstrated significant dose-response agonist activity on CHO-K1 / GLP1 R / Gal5 cells. To elaborate further, Molecule 11 exhibited effects comparable to the positive control (GLP-1 (7-37).Attorney Docket No.: 064630-503001 WO

[0287] The experiment of FIG. 20 evaluated the agonistic activity of the positive control and test samples targeting GLPIR. GLP-1 (7-37), serving as the positive control, demonstrated significant agonistic activity against CHO-K1 / GLP1 R / Ga15 cells. Both test samples, molecule 4 and molecule 10, demonstrated significant agonistic activity on CHO- K1 / GLP1 R / Ga15 cells.(b) GCGR agonist assay

[0288] cAMP accumulation assays were performed using the target expressing cells, CHO-K1 / GCGR / Ga15 cells. Results are shown in Table 3. The positive control used in the GCGR agonist assay was glucagon (1 -29).

[0289] Result of cAMP assay for positive control and test samples targeting GCGR is shown in FIG. 18A-18B. CHO-K1 / GCGR / Ga15 cells were incubated at 37 °C for 30 minutes with serially diluted positive control (Glucagon (1 -29)) and test samples (4, 7, 1 1 ). Each data point represents mean # SEM (n = 3).

[0290] The experiment of FIG. 18A evaluated the agonistic activity of the positive control and test samples targeting GCGR (glucagon receptor). Glucagon (1 -29), serving as the positive control, demonstrated significant agonistic activity against CHO-K1 / GCGR / Ga15 cells. FIG. 18A shows that test samples 4, 7 demonstrated significant agonistic activity against CHO- CHO-K1 / GCGR / Ga15.

[0291] In the experiment of FIG. 18B, the positive control, Glucagon (1 -29), demonstrated significant agonistic activity on CHO-K1 / GCGR / Ga 15 cells in a dosedependent manner. The test sample 11 demonstrated significant agonist activity in a dosedependent manner against CHO-K1 / GCGR / Ga15 cells, exhibiting effects comparable to the positive control.

[0292] (c) Apelin receptor agonist assay. The cAMP assay was performed using target cells, CHO-K1 / AGTRL1 / Ga15. Results are shown in Table 4. The positive control used in this assay was Apelin-13 TFA. The same protocol described above in (a) was followed except that the target cells were incubated at 37oC for 30 minutes with Forskolin (10 uM), serially diluted positive control, and test samples.Attorney Docket No.: 064630-503001 WO

[0293] Results of cAMP assay for positive control and test samples targeting AGTRL1 are shown in FIGs. 19A-19B. CHO-K1 / AGTRL 1 / Ga15 cells were incubated at 37 °C for 30 minutes with Forskolin (10 M), serially diluted positive control (Apelin-13 TFA), and test samples (3, 4, 5, 6, 7, 11 ) . Each data point represents mean + SEM (n = 3).

[0294] The experiment of FIG. 19A evaluated the agonist activity of the positive control and test samples targeting AGTRL1 (apelin receptor / APJ). Apelin-13 TFA, serving as the positive control, demonstrated significant agonist activity against CHO-K1 / AGTRL1 / Gal5 cells. FIG. 19A shows that test samples (3, 4, 5, 6, 7) demonstrated agonist activity against CHO-K1 / AGTRL1 / Gal5 cells. Notably. Molecule 4 demonstrated the most potent agonistic activity among the test samples.

[0295] The experiment of FIG. 19B evaluated the agonist activity of the positive control and test samples targeting AGTRL1 (apelin receptor / APJ). Apelin-13 TFA, serving as the positive control, demonstrated significant agonist activity against CHO-K1 / AGTRL1 / Gal5 cells. FIG. 19B shows test sample 1 1 demonstrated merely weak agonist activity against CHO-K1 / AGTRL1 / Gal5 cells at concentration of 100 nM.Table 2. GLP1 cAMP assayTable 3. GCGP cAMP assayAttorney Docket No.: 064630-503001 WOTable 4. Apelin cAMP assayTable 5. GLP1 cAMP assayExample 3

[0296] Exemplary fusion proteins are illustrated in FIGs. 1 -16.

[0297] While the present application has been described with reference to what are presently considered to be the preferred examples, it is to be understood that the application is not limited to the disclosed examples. To the contrary, the application is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims.

[0298] Enumerated EmbodimentsEnumerataed Embodiment 1 . A fusion protein comprising: a) an antigen-binding molecule capable of binding at least one muscle-inhibitory factor; b) a first peptide, the first peptide coupled to a first terminus of the antigen-binding molecule; andAttorney Docket No.: 064630-503001 WO c) a second peptide, the second peptide coupled to a second terminus of the antigen-binding molecule.Enumerataed Embodiment 2. A fusion protein comprising: a) a first region comprising a first Fab region capable of binding at least one muscle-inhibitory factor; b) a second region comprising a Fc region; c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein the first peptide and the second peptide are coupled to different termini.Enumerataed Embodiment 3. The fusion protein of any of the enumerated embodiments, further comprises a third peptide, the third peptide coupled to a third terminus of the antigen-binding molecule or a terminus of the first region or the second region, wherein the first peptide, the second peptide and the third peptide are coupled to different termini.Enumerataed Embodiment 4. The fusion protein of any of the enumerated embodiments, wherein the first peptide, the second peptide, and / or the third peptide comprises a therapeutic peptide.Enumerataed Embodiment 5. The fusion protein of any of the enumerated embodiments, wherein the therapeutic peptide is a metabolic peptide.Enumerataed Embodiment 6. The fusion protein of any of the preceding claims, wherein the metabolic peptide comprises a peptide selected from the group consisting of: GLP-1 , GLP-2, GIP, GCGP, apelin, Elabela, PYY, LEAP2, amylin, OXM, and analogs or functional variants thereof.Enumerataed Embodiment 7. The fusion protein of any of the enumerated embodiments, wherein the first peptide, the second peptide, and / or the third peptide comprises a peptide selected from the group consisting of: GCGP, GLP-1 , GIP, LEAP2, and analogs or functional variants thereof.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 8. The fusion protein of any of the enumerated embodiments, wherein the first peptide comprises GCGP, or an analog or functional variant thereof; and wherein the second peptide comprises GLP-1 , or an analog or functional variant thereof.Enumerataed Embodiment 9. The fusion protein of any of the enumerated embodiments, wherein the first peptide comprises GIP, or an analog or functional variant thereof; and wherein the second peptide comprises GLP-1 , or an analog or functional variant thereof.Enumerataed Embodiment 10. The fusion protein of any of the enumerated embodiments, wherein the first peptide comprises LEAP2, or an analog or functional variant thereof; and wherein the second peptide comprises GLP-1 , or an analog or functional variant thereof.Enumerataed Embodiment 11 . The fusion protein of any of the enumerated embodiments, wherein the third peptide comprises apelin, or an analog or functional variant thereof.Enumerataed Embodiment 12. The fusion protein of any of the enumerated embodiments, wherein the apelin comprises apelin-36, apelin-17, or apelin-13.Enumerataed Embodiment 13. The fusion protein of any of the enumerated embodiments, wherein the apelin comprises apelin-13.Enumerataed Embodiment 14. The fusion protein of any of the enumerated embodiments, wherein the third peptide comprises Elabela, or an analog or functional variant thereof.Enumerataed Embodiment 15. The fusion protein of any of the enumerated embodiments, wherein the Elabela comprises Elabela -32, Elabela -21 , or Elabela -1 1 .Enumerataed Embodiment 16. The fusion protein of any of the enumerated embodiments, wherein the Elabela comprises Elabela -32.Enumerataed Embodiment 17. The fusion protein of any of the enumerated embodiments, wherein the GLP-1 comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 1.Enumerataed Embodiment 18. The fusion protein of any of the enumerated embodiments, wherein the GCGP comprises an amino acid sequence of at least 80%, at least 85%, atAttorney Docket No.: 064630-503001 WO least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 12.Enumerataed Embodiment 19. The fusion protein of any of the enumerated embodiments, wherein the apelin comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 13, 72, and 73.Enumerataed Embodiment 20. The fusion protein of any of the enumerated embodiments, wherein the Elabela comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 77, 78, and 79.Enumerataed Embodiment 21 . The fusion protein of any of the enumerated embodiments, wherein the GIP comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 14.Enumerataed Embodiment 22. The fusion protein of any of the enumerated embodiments, wherein the GIP comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 15.Enumerataed Embodiment 23. The fusion protein of any of the enumerated embodiments, wherein the LEAP2 comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 16.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 24. The fusion protein of any of the enumerated embodiments, wherein the first Fab region comprises a light chain.Enumerataed Embodiment 25. The fusion protein of any of the enumerated embodiments, wherein the first Fab region comprises a heavy chain Fab portion.Enumerataed Embodiment 26. The fusion protein of any of the enumerated embodiments, wherein the first region further comprises a second Fab region.Enumerataed Embodiment 27. The fusion protein of any of the enumerated embodiments, wherein the second Fab region is capable of binding the at least one muscle-inhibitory factor.Enumerataed Embodiment 28. The fusion protein of any of the enumerated embodiments, wherein the second Fab region comprises a light chain.Enumerataed Embodiment 29. The fusion protein of any of the enumerated embodiments, wherein the second Fab region comprises a heavy chain Fab portion.Enumerataed Embodiment 30. The fusion protein of any of the enumerated embodiments, wherein at least one of the Fab regions binds the at least one muscle-inhibitory factor.Enumerataed Embodiment 31 . The fusion protein of any of the enumerated embodiments, wherein at least one of the Fab regions specifically binds the at least one muscle-inhibitory factor.Enumerataed Embodiment 32. The fusion protein of any of the enumerated embodiments, wherein the at least one muscle-inhibitory factor comprises myostatin.Enumerataed Embodiment 33. The fusion protein of any of the enumerated embodiments, wherein the at least one muscle-inhibitory factor comprises activin A.Enumerataed Embodiment 34. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises landogrozumab, trevogrumab, garetosmab, apitegromab, domagrozumab, stamulumab, or SRK-015.Enumerataed Embodiment 35. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises landogrozumab.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 36. The fusion protein of any of the enumerated embodiments, wherein at least one of the Fab regions comprises an antigen-binding fragment of landogrozumab, trevogrumab, garetosmab, apitegromab, domagrozumab, stamulumab, or SRK-015.Enumerataed Embodiment 37. The fusion protein of any of the enumerated embodiments, herein at least one of the Fab regions comprises an antigen-binding fragment of landogrozumab.Enumerataed Embodiment 38. The fusion protein of any of the enumerated embodiments, wherein at least one of the heavy chain Fab portions comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 .Enumerataed Embodiment 39. The fusion protein of any of the enumerated embodiments, wherein at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 2, a CDR2 having an amino acid sequence of SEQ ID NO: 3, and a CDR3 having an amino acid sequence of SEQ ID NO: 4.Enumerataed Embodiment 40. The fusion protein of any of the enumerated embodiments, wherein at least one of the light chains comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 5.Enumerataed Embodiment 41 . The fusion protein of any of the enumerated embodiments, wherein at least one of the light chains comprises a CDR1 having an amino acid sequence of SEQ ID NO: 6, a CDR2 having an amino acid sequence of SEQ ID NO: 7, and a CDR3 having an amino acid sequence of SEQ ID NO: 8.Enumerataed Embodiment 42. The fusion protein of any of the enumerated embodiments, wherein the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 43. The fusion protein of any of the enumerated embodiments, at least one of the heavy chain Fc portions comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 9 or SEQ ID NO: 10.Enumerataed Embodiment 44. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 .Enumerataed Embodiment 45. The fusion protein of any of the enumerated embodiments, wherein the heavy chain of the antigen-binding molecule further comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 9 or SEQ ID NO: 10.Enumerataed Embodiment 46. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 2, a CDR2 having an amino acid sequence of SEQ ID NO: 3, and a CDR3 having an amino acid sequence of SEQ ID NO: 4.Enumerataed Embodiment 47. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a light chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 5.Enumerataed Embodiment 48. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 6, a CDR2 having an amino acid sequence of SEQ ID NO: 7, and a CDR3 having an amino acid sequence of SEQ ID NO: 8.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 49. The fusion protein of any of the enumerated embodiments, wherein the first heavy chain Fc portion, the second heavy chain Fc portion, or both comprises one or more mutations that improve the stability of the fusion protein and / or a half-life of the fusion protein.Enumerataed Embodiment 50. The fusion protein of any of the enumerated embodiments, wherein the first heavy chain Fc portion, the second heavy chain Fc portion, or both comprises one or more mutations that reduce or abolish an effector function of the Fc region.Enumerataed Embodiment 51 . The fusion protein of any of the enumerated embodiments, wherein the first heavy chain Fc portion, the second heavy chain Fc portion, or both comprises one or more mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in lgG4, or any combination thereof.Enumerataed Embodiment 52. The fusion protein of any of the enumerated embodiments, wherein the first peptide is coupled to the first region.Enumerataed Embodiment 53. The fusion protein of any of the enumerated embodiments, wherein the first peptide is coupled to the second region.Enumerataed Embodiment 54. The fusion protein of any of the enumerated embodiments, wherein the second peptide is coupled to the first region.Enumerataed Embodiment 55. The fusion protein of any of the enumerated embodiments, wherein the second peptide is coupled to the second region.Enumerataed Embodiment 56. The fusion protein of any of the enumerated embodiments, wherein the third peptide is coupled to the first region.Enumerataed Embodiment 57. The fusion protein of any of the enumerated embodiments, wherein the third peptide is coupled to the second region.Enumerataed Embodiment 58. The fusion protein of any of the enumerated embodiments, wherein the first peptide is coupled to the N-terminus of the light chain of the first Fab region.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 59. The fusion protein of any of the enumerated embodiments, wherein the first peptide coupled to the N-terminus of the light chain of the first Fab region comprises GCGP, or an analog or functional variant thereof.Enumerataed Embodiment 60. The fusion protein of any of the enumerated embodiments, wherein the first peptide coupled to the N-terminus of the light chain of the first Fab region comprises GIP, or an analog or functional variant thereof.Enumerataed Embodiment 61 . The fusion protein of any of the enumerated embodiments, wherein the first peptide coupled to the N-terminus of the light chain of the first Fab region comprises LEAP2, or an analog or functional variant thereof.Enumerataed Embodiment 62. The fusion protein of any of the enumerated embodiments, wherein the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region.Enumerataed Embodiment 63. The fusion protein of any of the enumerated embodiments, wherein the second peptide coupled to the N-terminus of the heavy chain Fab portion of the first Fab region comprises GLP-1 , or an analog or functional variant thereof.Enumerataed Embodiment 64. The fusion protein of any of the enumerated embodiments, wherein the second peptide is coupled to the N-terminus of the first heavy chain Fc portion.Enumerataed Embodiment 65. The fusion protein of any of the enumerated embodiments, wherein the second peptide coupled to the N-terminus of the first heavy chain Fc portion comprises GLP-1 , or an analog or functional variant thereof.Enumerataed Embodiment 66. The fusion protein of any of the enumerated embodiments, wherein the third peptide is coupled to the N-terminus of the light chain of the second Fab region.Enumerataed Embodiment 67. The fusion protein of any of the enumerated embodiments, wherein the third peptide coupled to the N-terminus of the light chain of the second Fab region comprises GCGP, or an analog or functional variant thereof.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 68. The fusion protein of any of the enumerated embodiments, wherein the third peptide coupled to the N-terminus of the light chain of the second Fab region comprises GIP, or an analog or functional variant thereof.Enumerataed Embodiment 69. The fusion protein of any of the enumerated embodiments, wherein the third peptide coupled to the N-terminus of the light chain of the second Fab region comprises LEAP2, or an analog or functional variant thereof.Enumerataed Embodiment 70. The fusion protein of any of the enumerated embodiments, wherein the fourth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region.Enumerataed Embodiment 71 . The fusion protein of any of the enumerated embodiments, wherein the fourth peptide coupled to the N-terminus of the heavy chain Fab portion of the second Fab region comprises GLP-1 , or an analog or functional variant thereof.Enumerataed Embodiment 72. The fusion protein of any of the enumerated embodiments, wherein the third peptide is coupled to the C-terminus of the first heavy chain Fc portion.Enumerataed Embodiment 73. The fusion protein of any of the enumerated embodiments, wherein the third peptide coupled to the C-terminus of the first heavy chain Fc portion comprises apelin, or an analog or functional variant thereof.Enumerataed Embodiment 74. The fusion protein of any of the enumerated embodiments, wherein the third peptide coupled to the C-terminus of the first heavy chain Fc portion comprises Elabela, or an analog or functional variant thereof.Enumerataed Embodiment 75. The fusion protein of any of the enumerated embodiments, wherein the third peptide is coupled to the C-terminus of the light chain of the first Fab region.Enumerataed Embodiment 76. The fusion protein of any of the enumerated embodiments, wherein the third peptide coupled to the C-terminus of the light chain of the first Fab region comprises apelin, or an analog or functional variant thereof.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 77. The fusion protein of any of the enumerated embodiments, wherein the third peptide coupled to the C-terminus of the light chain of the first Fab region comprises Elabela, or an analog or functional variant thereof.Enumerataed Embodiment 78. The fusion protein of any of the enumerated embodiments, wherein the fusion protein further comprises a hinge region.Enumerataed Embodiment 79. The fusion protein of any of the preceding claims, wherein the hinge region comprises a lgG1 hinge region.Enumerataed Embodiment 80. The fusion protein of any of the preceding claims, wherein the hinge region comprises a lgG4 hinge region.Enumerataed Embodiment 81 . The fusion protein of any of the enumerated embodiments, wherein the hinge region comprises at least one disulfide bond.Enumerataed Embodiment 82. The fusion protein of any of the enumerated embodiments, wherein the hinge region comprises two hinge sequences.Enumerataed Embodiment 83. The fusion protein of any of the enumerated embodiments, wherein the hinge region is N-terminal to the second region.Enumerataed Embodiment 84. The fusion protein of any of the enumerated embodiments, wherein the hinge region connects the first region and the second region.Enumerataed Embodiment 85. The fusion protein of any of the enumerated embodiments, wherein the hinge region connects at least one of the peptides and the second region.Enumerataed Embodiment 86. The fusion protein of any of the enumerated embodiments, wherein the hinge region comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to SEQ ID NO: 17.Enumerataed Embodiment 87. The fusion protein of any of the enumerated embodiments, wherein the hinge region comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 76.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 88. The fusion protein of any of the enumerated embodiments, wherein the hinge region comprises one or more mutations that reduce or eliminate an effector function of the Fc region.Enumerataed Embodiment 89. The fusion protein of any of the enumerated embodiments, wherein the hinge region comprises one or more mutations that promote formation of the fusion protein.Enumerataed Embodiment 90. The fusion protein of any of the enumerated embodiments, wherein the hinge region comprises one or more mutations corresponding to S228P in lgG4, F234A in lgG4, L235A in lgG4, or any combination thereof.Enumerataed Embodiment 91 . The fusion protein of any of the enumerated embodiments, wherein the hinge region comprises one or more mutations corresponding to S228P in IgG 1 , L234A in IgG 1 , L235A in IgG 1 , or any combination thereof.Enumerataed Embodiment 92. The fusion protein of any of the enumerated embodiments, wherein the first region is N-terminal to the second region.Enumerataed Embodiment 93. The fusion protein of any of the enumerated embodiments, wherein the first region is C-terminal to the second region.Enumerataed Embodiment 94. The fusion protein of any of the enumerated embodiments, further comprises a fourth peptide, the fourth peptide coupled to a fourth terminus of the antigen-binding molecule or a terminus of the first region or the second region, wherein the first peptide, the second peptide, the third peptide and the fourth peptide are coupled to different termini.Enumerataed Embodiment 95. The fusion protein of any of the enumerated embodiments, further comprises a fifth peptide, the fifth peptide coupled to a fifth terminus of the antigenbinding molecule or a terminus of the first region or the second region, wherein the first peptide, the second peptide, the third peptide, the fourth peptide and the fifth peptide are coupled to different termini.Enumerataed Embodiment 96. The fusion protein of any of the enumerated embodiments, further comprises a sixth peptide, the sixth peptide coupled to a sixth terminus of the antigen-binding molecule or a terminus of the first region or the second region, whereinAttorney Docket No.: 064630-503001 WO the first peptide, the second peptide, the third peptide, the fourth peptide, the fifth peptide, and the sixth peptide are coupled to different termini.Enumerataed Embodiment 97. The fusion protein of any of the enumerated embodiments, wherein the fourth peptide, the fifth peptide, and / or the sixth peptide comprises a peptide selected from the group consisting of: GCGP, GLP-1 , GIP, LEAP2, and analogs or functional variants thereof.Enumerataed Embodiment 98. The fusion protein of any of the enumerated embodiments, wherein at least one of the peptides is coupled to the first region or the second region through a linker.Enumerataed Embodiment 99. The fusion protein of any of the enumerated embodiments, wherein the linker comprises (GGGGS)0-8, (EAAAK)0-8, or combinations thereof.Enumerataed Embodiment 100. The fusion protein of any of the enumerated embodiments, wherein the linker comprises an amino acid sequence of one of SEQ ID NOs: 18-22.Enumerataed Embodiment 101. The fusion protein of any of the enumerated embodiments, wherein at least one of the light chains and the heavy chain Fab portions comprises a signal peptide.Enumerataed Embodiment 102. The fusion protein of any of the preceding claims, wherein at least one of the peptides is coupled to the terminus covalently.Enumerataed Embodiment 103. The fusion protein of any of the preceding claims, wherein at least one of the peptides is coupled to the terminus non-covalently.Enumerataed Embodiment 104. The fusion protein of any of the preceding claims, wherein the antigen-binding molecule is an immunoglobulin.Enumerataed Embodiment 105. The fusion protein of any of the preceding claims, wherein the first Fab region and / or the second Fab region comprises a Fab region of an immunoglobulin.Enumerataed Embodiment 106. The fusion protein of any of the preceding claims, wherein the Fc region comprises a Fc region of an immunoglobulin.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 107. The fusion protein of any of the preceding claims, wherein the light chain of the first Fab region and / or the light chain of the second Fab region comprises a light chain of an immunoglobulin.Enumerataed Embodiment 108. The fusion protein of any of the preceding claims, wherein the heavy chain Fab portion of the first Fab region and / or the heavy chain Fab portion of the second Fab region comprises a Fab portion of a heavy chain of an immunoglobulin.Enumerataed Embodiment 109. The fusion protein of any of the preceding claims, wherein the first heavy chain Fc portion and / or the second heavy chain Fc portion comprises a Fc portion of a Fc region of an immunoglobulin.Enumerataed Embodiment 110. The fusion protein of any of the preceding claims, wherein the immunoglobulin is an IgG.Enumerataed Embodiment 11 1. The fusion protein of any of the preceding claims, wherein the immunoglobulin is an lgG4.Enumerataed Embodiment 112. The fusion protein of any of the preceding claims, wherein the immunoglobulin is an IgG 1 .Enumerataed Embodiment 113. The fusion protein of any of the preceding claims, wherein each of the termini of the fusion protein is coupled to a peptide.Enumerataed Embodiment 114. The fusion protein of any of the preceding claims, wherein the fusion protein comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 80, 84, 88, and 92.Enumerataed Embodiment 115. The fusion protein of any of the preceding claims, wherein the fusion protein comprises an amino acid sequence of any one of SEQ ID NOs: 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 80, 84, 88, and 92.Enumerataed Embodiment 116. The fusion protein of any of the preceding claims, wherein the fusion protein is encoded by a nucleic acid comprising a nucleotide sequence of at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%,Attorney Docket No.: 064630-503001 WO at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 25, 29, 33, 37, 41 , 45, 49, 53, 57, 61 , 65, 69, 81 , 85, 89, and 93.Enumerataed Embodiment 117. The fusion protein of any of the preceding claims, wherein the fusion protein is encoded by a nucleic acid comprising a nucleotide sequence of any one of SEQ ID NOs: 25, 29, 33, 37, 41 , 45, 49, 53, 57, 61 , 65, 69, 81 , 85, 89, and 93.Enumerataed Embodiment 118. The fusion protein of any of the preceding claims, wherein the fusion protein comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 82, 86, 90, and 94.Enumerataed Embodiment 119. The fusion protein of any of the preceding claims, wherein the fusion protein comprises an amino acid sequence of any one of SEQ ID NOs: 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 82, 86, 90, and 94.Enumerataed Embodiment 120. The fusion protein of any of the preceding claims, wherein the fusion protein is encoded by a nucleic acid comprising a nucleotide sequence of at least 70%, at least 75%, at least 80%, at least 85, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 27, 31 , 35, 39, 43, 47, 51 , 55, 59, 63, 67, 71 , 83, 87, 91 , and 95.Enumerataed Embodiment 121 . The fusion protein of any of the preceding claims, wherein the fusion protein is encoded by a nucleic acid comprising a nucleotide sequence of any one of SEQ ID NOs: 27, 31 , 35, 39, 43, 47, 51 , 55, 59, 63, 67, 71 , 83, 87, 91 , and 95.Enumerataed Embodiment 122. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region,Attorney Docket No.: 064630-503001 WO wherein:(1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein each of the first heavy chain Fc portion and the second heavy chain Fc portion comprises mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in igG4, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,(2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion;(3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region of the first region; and the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region,(4) the fusion protein further comprises a third peptide and a fourth peptide, wherein the third peptide is coupled to the N-terminus of the light chain of the second Fab region of the first region; and the fourth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region,(5) each of the first peptide, the second peptide, the third peptide, and the fourth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)s, and(6) each of the first peptide and the third peptide comprises GCGP, or an analog or functional variant thereof; wherein each of the second peptide and the fourth peptide comprises GLP-1 , or an analog or functional variant thereof.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 123. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) The first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein each of the first heavy chain Fc portion and the second heavy chain Fc portion comprises mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in lgG4, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,(2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion,(3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region,(4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C-terminus of the first heavy chain Fc portion;Attorney Docket No.: 064630-503001 WO the fourth peptide is coupled to the N-terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N-terminus of the Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the second heavy chain Fc portion,(5) each of the first peptide, the second peptide, the fourth peptide, and the fifth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3; and each of the third peptide and the sixth peptide is coupled to the second region via a linker, wherein the linker has an amino acid sequence of (GGGGS)s, and(6) each of the first peptide and the fourth peptide comprises GCGP, or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 , or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin, or an analog or functional variant thereof.Enumerataed Embodiment 124. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein each of the first Fc portion and the second Fc portion comprises mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in igG4,Attorney Docket No.: 064630-503001 WO wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,(2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion,(3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the Fab portion of the first Fab region,(4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C-terminus of the first heavy chain Fc portion ; the fourth peptide is coupled to the N-terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the second heavy chain Fc portion,(5) each of the first peptide, the second peptide, the fourth peptide, and the fifth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4; and each of the third peptide and the sixth peptide is coupled to the second region via a linker, wherein the linker has an amino acid sequence of (GGGGS)s, and(6) each of the first peptide and the fourth peptide comprises GCGP, or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 , or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin, or an analog or functional variant thereof.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 125. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) The first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion,(2) the C-terminus of the first heavy chain Fc portion of the second region is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region via a linker having an amino acid sequence of (GGGGS)2, and the C-terminus of the second heavy chain Fc portion is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region via a linker having an amino acid sequence of (GGGGS)2,(3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the first heavy chain Fc portion via a first hinge sequence,(4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C-terminus of the light chain of the first Fab region; the fourth peptide is coupled to the N-terminus of the light chain of the second Fab region;Attorney Docket No.: 064630-503001 WO the fifth peptide is coupled to the N-terminus of the second heavy chain Fc portion via a second hinge sequence; and the sixth peptide is coupled to the C- terminus of the light chain,(5) the first hinge sequences and the second hinge sequences comprise mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4, and are linked via at least two disulfide bonds,(6) each of the first peptide, the third peptide, the fourth peptide, and the sixth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4; the second peptide is coupled to the first hinge sequence via a linker, wherein the linker has an amino acid sequence of (GGGGS)s; and the fifth peptide is coupled to the second hinge sequence via a linker, wherein the linker has an amino acid sequence of (GGGGS)s, and(7) each of the first peptide and the fourth peptide comprises GCGP, or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 , or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin, or an analog or functional variant thereof.Enumerataed Embodiment 126. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) The first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; andAttorney Docket No.: 064630-503001 WO the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,(2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion,(3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region ion,(4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C-terminus of the light chain of the first Fab region; the fourth peptide is coupled to the N-terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the light chain of the second Fab region,(5) each of the first peptide, the second peptide, the fourth peptide, and the fifth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)s; and each of the third peptide and the sixth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4, and(6) each of the first peptide and the fourth peptide comprises GCGP, or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptideAttorney Docket No.: 064630-503001 WO comprises GLP-1 , or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin, or an analog or functional variant thereof.Enumerataed Embodiment 127. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) The first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,(2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion,(3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region;(4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C-terminus of the light chain of the first Fab region;Attorney Docket No.: 064630-503001 WO the fourth peptide is coupled to the N-terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N-terminus of the Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the light chain of the second Fab region of,(5) each of the first peptide, the second peptide, the fourth peptide, and the fifth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3; and each of the third peptide and the sixth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)s, and(6) each of the first peptide and the fourth peptide comprises GCGP, or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 , or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin, or an analog or functional variant thereof.Enumerataed Embodiment 128. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion,Attorney Docket No.: 064630-503001 WO wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,(2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion,(3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region;(4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C-terminus of the light chain of the first Fab region; the fourth peptide is coupled to the N-terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the light chain of the second Fab region,(5) each of the first peptide, the second peptide, the fourth peptide, and the fifth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)s; and each of the third peptide and the sixth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)e, and(6) each of the first peptide and the fourth peptide comprises GCGP, or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 , or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin, or an analog or functional variant thereof.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 129. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) The first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,(2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion,(3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the Fab portion of the first Fab region,(4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C-terminus of the first heavy chain Fc portion; the fourth peptide is coupled to the N-terminus of the light chain of the second Fab region;Attorney Docket No.: 064630-503001 WO the fifth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the second heavy chain Fc portion,(5) each of the first peptide, the second peptide, the fourth peptide, and the fifth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4; and each of the third peptide and the sixth peptide is coupled to the second region via a linker, wherein the linker has an amino acid sequence of (GGGGS)s, and(6) each of the first peptide and the fourth peptide comprises GIP, or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 , or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin, or an analog or functional variant thereof.Enumerataed Embodiment 130. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,Attorney Docket No.: 064630-503001 WO(2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion,(3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the Fab portion of the first Fab region,(4) the fusion protein further comprises a third peptide and a fourth peptide, wherein: the third peptide is coupled to the N-terminus of the light chain of the second Fab region; and the fourth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region,(5) Wherein each of the first peptide, the second peptide, the third peptide, and the fourth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4, and(6) each of the first peptide and the third peptide comprises GIP, or an analog or functional variant thereof; wherein each of the second peptide and the fourth peptide comprises GLP-1 , or an analog or functional variant thereof.Enumerataed Embodiment 131 . A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; andAttorney Docket No.: 064630-503001 WO the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,(2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion,(3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the Fab portion of the first Fab region,(4) the fusion protein further comprises a third peptide and a fourth peptide, wherein: the third peptide is coupled to the N-terminus of the light chain of the second Fab region; and the fourth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region,(5) each of the first peptide, the second peptide, the third peptide, and the fourth peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4, and(6) each of the first peptide and the third peptide comprises LEAP2, or an analog or functional variant thereof; wherein each of the second peptide and the fourth peptide comprises GLP-1 , or an analog or functional variant thereof.Enumerataed Embodiment 132. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; andAttorney Docket No.: 064630-503001 WO d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,(2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion,(3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region of; and the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region,(4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C-terminus of the light chain of the first Fab region; the fourth peptide is coupled to the N-terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the light chain of the second Fab region,(5) each of the peptides is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)s, andAttorney Docket No.: 064630-503001 WO(6) each of the first peptide and the fourth peptide comprises GCGP, or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 , or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin, or an analog or functional variant thereof.Enumerataed Embodiment 133. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,(2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion,(3) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; and the second peptide is coupled to the N-terminus of the heavy chain Fab portion of the first Fab region;Attorney Docket No.: 064630-503001 WO(4) the fusion protein further comprises a third peptide, a fourth peptide, a fifth peptide, and a sixth peptide, wherein: the third peptide is coupled to the C-terminus of the light chain of the first Fab region; the fourth peptide is coupled to the N-terminus of the light chain of the second Fab region; the fifth peptide is coupled to the N-terminus of the heavy chain Fab portion of the second Fab region; and the sixth peptide is coupled to the C-terminus of the light chain of the second Fab region,(5) each of the peptides is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)3, and(6) each of the first peptide and the fourth peptide comprises GCGP, or an analog or functional variant thereof; wherein each of the second peptide and the fifth peptide comprises GLP-1 , or an analog or functional variant thereof, wherein each of the third peptide and the sixth peptide comprises apelin, or an analog or functional variant thereof.Enumerataed Embodiment 134. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein each of the first heavy chain Fc portion and the second heavy chain FcAttorney Docket No.: 064630-503001 WO portion comprises mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in igG4, wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,(2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion,(3) the first peptide is coupled to the C-terminus of the first heavy chain Fc portion; and the second peptide is coupled to the C-terminus of the second heavy chain Fc portion,(4) each of the first peptide and the second peptide is coupled to the second region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4-6, and(5) each of the first peptide and the second peptide comprises apelin, or an analog or functional variant thereof.Enumerataed Embodiment 135. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein each of the first heavy chain Fc portion and the second heavy chain Fc portion comprises mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in igG4,Attorney Docket No.: 064630-503001 WO wherein a hinge region connects the first region and the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,(2) the C-terminus of the heavy chain Fab portion of the first Fab region is coupled to the N-terminus of the first heavy chain Fc portion, and the C-terminus of the heavy chain Fab portion of the second Fab region is coupled to the N-terminus of the second heavy chain Fc portion,(3) the first peptide is coupled to the C-terminus of the light chain of the first Fab region; and the second peptide is coupled to the C-terminus of the light chain of the second Fab region,(4) each of the first peptide and the second peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4-6, and(5) each of the first peptide and the second peptide comprises apelin, or an analog or functional variant thereof.Enumerataed Embodiment 136. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein each of the first heavy chain Fc portion and the second heavy chain Fc portion comprises mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in igG4,Attorney Docket No.: 064630-503001 WO(2) the fusion protein further comprises a hinge region at the N-terminus of the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,(3) the N-terminus of the heavy chain Fab portion of the first Fab region is coupled to the C-terminus of the first heavy chain Fc portion, and the N-terminus of the heavy chain Fab portion of the second Fab region is coupled to the C-terminus of the second heavy chain Fc portion,(4) the first peptide is coupled to the C-terminus of the light chain of the first Fab region; and the second peptide is coupled to the C-terminus of the light chain of the second Fab region,(5) each of the first peptide and the second peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4-6, and(6) each of the first peptide and the second peptide comprises apelin, or an analog or functional variant thereof.Enumerataed Embodiment 137. A fusion protein comprising: a. a first region comprising a first Fab region capable of binding myostatin; b. a second region comprising a Fc region; c. a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d. a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein:(1 ) the first region further comprises a second Fab region that binds myostatin; wherein each of the first Fab region and the second Fab region comprises a light chain and a heavy chain Fab portion; and the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion, wherein each of the first heavy chain Fc portion and the second heavy chain Fc portion comprises mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in igG4,Attorney Docket No.: 064630-503001 WO(2) the fusion protein further comprises a hinge region at the N-terminus of the second region, the hinge region comprising (a) mutations corresponding to S228P in lgG4, F234A in lgG4, and L235A in lgG4; and (b) two disulfide bonds,(3) the N-terminus of the heavy chain Fab portion of the first Fab region is coupled to the C-terminus of the first heavy chain Fc portion, and the N-terminus of the heavy chain Fab portion of the second Fab region is coupled to the C-terminus of the second heavy chain Fc portion,(4) the first peptide is coupled to the C-terminus of the first heavy chain Fc portion; and the second peptide is coupled to the C-terminus of the second heavy chain Fc portion,(5) each of the first peptide and the second peptide is coupled to the first region via a linker, wherein the linker has an amino acid sequence of (GGGGS)4-6, and(6) each of the first peptide and the second peptide comprises apelin, or an analog or functional variant thereof.Enumerataed Embodiment 138. A nucleic acid comprising nucleic acid sequences encoding the fusion protein of any one of the preceding claims.Enumerataed Embodiment 139. A vector comprising the nucleic acid of any of the preceding claims.Enumerataed Embodiment 140. A cell comprising the vector of any of the preceding claims.Enumerataed Embodiment 141 . A pharmaceutical composition comprising the fusion protein, the vector, or the cell of any one of the preceding claims.Enumerataed Embodiment 142. A method of treating a disease in a subject in need thereof, comprising administering the fusion protein or the pharmaceutical composition of any one of the preceding claims to the subject.Enumerataed Embodiment 143. The method of any of the preceding claims, wherein the disease is a metabolic disease.Enumerataed Embodiment 144. The method of any of the preceding claims, wherein the disease is a muscle wasting disease.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 145. The method of any of the preceding claims, wherein the metabolic disease is obesity, Type 1 diabetes, Type 2 diabetes, metabolic syndrome, insulin resistance, obesity-related heart failure, obesity-associated pulmonary arterial hypertension, fatty liver disease, MASH, or MASLD.Enumerataed Embodiment 146. The method of any of the preceding claims, wherein the administration results in lowered plasma glucose, reduced gastric and / or intestinal mobility, reduced gastric and / or intestinal emptying, reduced food intake, body weight loss, or any combination thereof in the subject, compared to a control subject.Enumerataed Embodiment 147. The method of any of the preceding claims, wherein the administration results in positive inotropic effects, myocardial protection, lowered systolic blood pressure, cardiac improvement, renoprotection, reduced inflammation, muscle regeneration, muscle growth, muscle adaptation, or any combination thereof in the subject, compared to a control subject.Enumerataed Embodiment 148. The method of any of the preceding claims, wherein the administration results in loss of fat mass in the subjectEnumerataed Embodiment 149. The method of any of the preceding claims, wherein the administration results in muscle preservation or reduced muscle loss in the subject as compared to a control subject.Enumerataed Embodiment 150. The method of any of the preceding claims, wherein the reduced muscle loss comprises less than about 90%, less than about 80%, less than about 70%, less than about 60%, less than about 50%, or less than over about 50% of a muscle loss level in a control subject about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 9 months, about 12 months, or after 12 months after the administration.Enumerataed Embodiment 151. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises trevogrumab.Enumerataed Embodiment 152. The fusion protein of any of the enumerated embodiments, wherein at least one of the heavy chain Fab portions comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, atAttorney Docket No.: 064630-503001 WO least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 96.Enumerataed Embodiment 153. The fusion protein of any of the enumerated embodiments, wherein at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 97, a CDR2 having an amino acid sequence of SEQ ID NO: 98, and a CDR3 having an amino acid sequence of SEQ ID NO: 99.Enumerataed Embodiment 154. The fusion protein of any of the enumerated embodiments, wherein at least one of the light chains comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to SEQ ID NO: 100.Enumerataed Embodiment 155. The fusion protein of any of the enumerated embodiments, wherein at least one of the light chains comprises a CDR1 having an amino acid sequence of SEQ ID NO: 101 , a CDR2 having an amino acid sequence of SEQ ID NO: 102, and a CDR3 having an amino acid sequence of SEQ ID NO: 103.Enumerataed Embodiment 156. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 96.Enumerataed Embodiment 157. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 97, a CDR2 having an amino acid sequence of SEQ ID NO: 98, and a CDR3 having an amino acid sequence of SEQ ID NO: 99.Enumerataed Embodiment 158. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a light chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 100.Attorney Docket No.: 064630-503001 WOEnumerataed Embodiment 159. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 101 , a CDR2 having an amino acid sequence of SEQ ID NO: 102, and a CDR3 having an amino acid sequence of SEQ ID NO: 103.Enumerataed Embodiment 160. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises garetosmab.Enumerataed Embodiment 161. The fusion protein of any of the enumerated embodiments, wherein at least one of the heavy chain Fab portions comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 104.Enumerataed Embodiment 162. The fusion protein of any of the enumerated embodiments, wherein at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 105, a CDR2 having an amino acid sequence of SEQ ID NO: 106, and a CDR3 having an amino acid sequence of SEQ ID NO: 107.Enumerataed Embodiment 163. The fusion protein of any of the enumerated embodiments, wherein at least one of the light chains comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to SEQ ID NO: 108.Enumerataed Embodiment 164. The fusion protein of any of the enumerated embodiments, wherein at least one of the light chains comprises a CDR1 having an amino acid sequence of SEQ ID NO: 109, a CDR2 having an amino acid sequence of SEQ ID NO: 110, and a CDR3 having an amino acid sequence of SEQ ID NO: 11 1.Enumerataed Embodiment 165. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 104.Enumerataed Embodiment 166. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a heavy chain comprising a CDR1Attorney Docket No.: 064630-503001 WO having an amino acid sequence of SEQ ID NO: 105, a CDR2 having an amino acid sequence of SEQ ID NO: 106, and a CDR3 having an amino acid sequence of SEQ ID NO: 107.Enumerataed Embodiment 167. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a light chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 108.Enumerataed Embodiment 168. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 109, a CDR2 having an amino acid sequence of SEQ ID NO: 110, and a CDR3 having an amino acid sequence of SEQ ID NO: 1 1 1.Enumerataed Embodiment 169. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises apitegromab.Enumerataed Embodiment 170. The fusion protein of any of the enumerated embodiments, wherein at least one of the heavy chain Fab portions comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 1 12.Enumerataed Embodiment 171. The fusion protein of any of the enumerated embodiments, wherein at least one of the heavy chain Fab portions comprises a CDR1 having an amino acid sequence of SEQ ID NO: 1 13, a CDR2 having an amino acid sequence of SEQ ID NO: 114, and a CDR3 having an amino acid sequence of SEQ ID NO: 115.Enumerataed Embodiment 172. The fusion protein of any of the enumerated embodiments, wherein at least one of the light chains comprises an amino acid sequence of at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to SEQ ID NO: 1 16.Enumerataed Embodiment 173. The fusion protein of any of the enumerated embodiments, wherein at least one of the light chains comprises a CDR1 having an amino acid sequenceAttorney Docket No.: 064630-503001 WO of SEQ ID NO: 117, a CDR2 having an amino acid sequence of SEQ ID NO: 118, and a CDR3 having an amino acid sequence of SEQ ID NO: 119.Enumerataed Embodiment 174. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 112.Enumerataed Embodiment 175. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a heavy chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 1 13, a CDR2 having an amino acid sequence of SEQ ID NO: 114, and a CDR3 having an amino acid sequence of SEQ ID NO: 115.Enumerataed Embodiment 176. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a light chain comprising an amino acid sequence of at least 80%, at least 85%, at least 90%, at least 90%, at least 91 %, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 116.Enumerataed Embodiment 177. The fusion protein of any of the enumerated embodiments, wherein the antigen-binding molecule comprises a light chain comprising a CDR1 having an amino acid sequence of SEQ ID NO: 1 17, a CDR2 having an amino acid sequence of SEQ ID NO: 118, and a CDR3 having an amino acid sequence of SEQ ID NO: 1 19.Enumerataed Embodiment 178. The fusion protein of any of the enumerated embodiments, wherein at least one of the peptides is GLP-1 , and wherein the fusion protein comprises a EC50 value of less than about 5-fold, less than about 4-fold, less than about 3-fold, or less than about 2-fold of a EC50 value of a control.Enumerataed Embodiment 179. The fusion protein of any of the enumerated embodiments, wherein the control is GLP-1 (1 -37).Enumerataed Embodiment 180. The fusion protein of any of the enumerated embodiments, wherein at least one of the peptides is GCGP, wherein the fusion protein comprises aAttorney Docket No.: 064630-503001 WOEC50 value of less than about 5-fold, less than about 4-fold, less than about 3-fold, or less than about 2-fold of a EC50 value of a control.Enumerataed Embodiment 181. The fusion protein of any of the enumerated embodiments, wherein the control is glucagon (1 -29).Enumerataed Embodiment 182. The fusion protein of any of the enumerated embodiments, wherein at least one of the peptides is apelin, wherein the fusion protein comprises a EC50 value of less than about 5-fold, less than about 4-fold, less than about 3-fold, or less than about 2-fold of a EC50 value of a control.Enumerataed Embodiment 183. The fusion protein of any of the enumerated embodiments, wherein the control is apelin 13.

[0299] All publications, patents and patent applications are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety. Specifically, the sequences associated with each accession numbers provided herein including for example accession numbers and / or biomarker sequences (e.g. protein and / or nucleic acid) provided in the Tables or elsewhere, are incorporated by reference in its entirely.

[0300] The scope of the claims should not be limited by the embodiments and examples, but should be given the broadest interpretation consistent with the description as a whole.Attorney Docket No.: 064630-503001 WOExample SequencesAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WOAttorney Docket No.: 064630-503001 WO

Claims

Attorney Docket No.: 064630-503001 WOCLAIMS:1 . A fusion protein comprising: a) a first region comprising a first Fab region capable of binding at least one muscle-inhibitory factor; b) a second region comprising a Fc region; c) a first peptide, the first peptide coupled to a terminus of the first region or the second region; and d) a second peptide, the second peptide coupled to a terminus of the first region or the second region, wherein the first peptide and the second peptide are coupled to different termini.

2. The fusion protein of claim 1 , further comprises a third peptide, the third peptide coupled to a third terminus of the antigen-binding molecule or a terminus of the first region or the second region, wherein the first peptide, the second peptide and the third peptide are coupled to different termini.

3. The fusion protein of any one of claims 1 -2, wherein the first peptide, the second peptide, and / or the third peptide comprises a metabolic peptide selected from the group consisting of: GLP-1 , GLP-2, GIP, GCGP, apelin, Elabela, PYY, LEAP2, amylin, OXM, and analogs or functional variants thereof.

4. The fusion protein of any one of claims 1 -3, wherein the first Fab region comprises a light chain and a heavy chain Fab portion.

5. The fusion protein of any one of claims 1 -4, wherein the first region further comprises a second Fab region.

6. The fusion protein of claim 5, wherein the second Fab region is capable of binding the at least one muscle-inhibitory factor.

7. The fusion protein of any one of claims 5-6, wherein the second Fab region comprises a light chain and a heavy chain Fab portion.

8. The fusion protein of any one of claims 1 -7, wherein the at least one muscle- inhibitory factor comprises myostatin.Attorney Docket No.: 064630-503001 WO9. The fusion protein of any one of claims 1 -7, wherein the at least one muscle- inhibitory factor comprises activin A.

10. The fusion protein of any one of claims 1 -7, wherein at least one of the Fab regions comprises an antigen-binding fragment of landogrozumab, trevogrumab, garetosmab, apitegromab, domagrozumab, stamulumab, or SRK-015.1 1 . The fusion protein of any one of claims 1 -10, wherein the fusion protein further comprises a hinge region.

12. The fusion protein of claim 1 1 , wherein the hinge region comprises one or more mutations corresponding to S228P in lgG4, F234A in lgG4, L235A in lgG4, or any combination thereof.

13. The fusion protein of claim 1 1 , wherein the hinge region comprises one or more mutations corresponding to S228P in IgG 1 , L234A in IgG 1 , L235A in IgG 1 , or any combination thereof.

14. The fusion protein of any one of claims 1 -13, wherein at least one of the peptides is coupled to the first region or the second region through a linker.

15. The fusion protein of claim 14, wherein the linker comprises (GGGGS)0-8, (EAAAK)0-8, or combinations thereof.

16. The fusion protein of any one claims 1 -15, wherein the Fc region comprises a first heavy chain Fc portion and a second heavy chain Fc portion.

17. The fusion protein of claim 16, wherein the first heavy chain Fc portion, the second heavy chain Fc portion, or both comprises one or more mutations that improve the stability of the fusion protein and / or a half-life of the fusion protein.

18. The fusion protein of claim 16, wherein the first heavy chain Fc portion, the second heavy chain Fc portion, or both comprises one or more mutations that reduce or abolish an effector function of the Fc region.

19. The fusion protein of claim 16, wherein the first heavy chain Fc portion, the second heavy chain Fc portion, or both comprises one or more mutations corresponding to M252Y in lgG4, S254T in lgG4, T256E in lgG4, or any combination thereof.

20. The fusion protein of any one of claims 1 -19, wherein the first region is N-terminal to the second region.Attorney Docket No.: 064630-503001 WO21 . The fusion protein of claim 20, wherein: (1 ) the first peptide is coupled to the N- terminus of the light chain of the first Fab region; and (2) the second peptide is coupled to the N-terminus of the first heavy chain Fc portion, wherein the first peptide comprises GCGP, or an analog or functional variant thereof, and the second peptide comprises GLP-1 , or an analog or functional variant thereof.

22. The fusion protein of claim 21 , further comprises a third peptide, wherein the third peptide is coupled to the C-terminus of the first heavy chain Fc portion, and wherein the third peptide comprises apelin, or an analog or functional variant thereof.

23. The fusion protein of claim 20, the fusion protein further comprises a third peptide, wherein (1 ) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; (2) the second peptide is coupled to the N-terminus of the first heavy chain Fc portion; and (3) the third peptide is coupled to the C-terminus of the light chain of the first Fab region, wherein the first peptide comprises GCGP, or an analog or functional variant thereof, the second peptide comprises GLP-1 , or an analog or functional variant thereof, and the third peptide comprises apelin, or an analog or functional variant thereof.

24. The fusion protein of claim 20, wherein: (1 ) the first peptide is coupled to the N- terminus of the light chain of the first Fab region; and (2) the second peptide is coupled to the N-terminus of the first heavy chain Fc portion, wherein the first peptide comprises GIP, or an analog or functional variant thereof, and the second peptide comprises GLP-1 , or an analog or functional variant thereof.

25. The fusion protein of claim 24, further comprises a third peptide, wherein the third peptide is coupled to the C-terminus of the first heavy chain Fc portion, and wherein the third peptide comprises apelin, or an analog or functional variant thereof.

26. The fusion protein of claim 24, further comprises a third peptide, wherein the third peptide is coupled to the C-terminus of the light chain of the first Fab region, and wherein the third peptide comprises apelin, or an analog or functional variant thereof.

27. The fusion protein of claim 20, wherein: (1 ) the first peptide is coupled to the N- terminus of the light chain of the first Fab region; and (2) the second peptide is coupled to the N-terminus of the first heavy chain Fc portion, wherein the firstAttorney Docket No.: 064630-503001 WO peptide comprises LEAP2, or an analog or functional variant thereof, and the second peptide comprises GLP-1 , or an analog or functional variant thereof.

28. The fusion protein of claim 20, wherein the fusion protein further comprises a second heavy chain Fc portion, wherein the first peptide is coupled to the C-terminus of the first heavy chain Fc portion, the second peptide is coupled to the C-terminus of the second heavy chain Fc portion, and the first peptide and the second peptide comprises apelin, or an analog or functional variant thereof.

29. The fusion protein of claim 20, wherein the fusion protein further comprises a second Fab region, wherein the first peptide is coupled to the C-terminus of the light chain of the first Fab region, the second peptide is coupled to the C-terminus of the light chain of the second Fab region, and the first peptide and the second peptide comprises apelin, or an analog or functional variant thereof.

30. The fusion protein of any one of claims 1 -19, wherein the first region is C-terminal to the second region.31 . The fusion protein of claim 30, wherein the hinge region connects at least one of the peptides and the second region.

32. The fusion protein of claim 30, wherein the hinge region is N-terminal to the second region.

33. The fusion protein of any one of claims 30-32, wherein: (1 ) the first peptide is coupled to the N-terminus of the light chain of the first Fab region; (2) the second peptide is coupled to the N-terminus of the first heavy chain Fc portion via a first hinge sequence; (3) the fusion protein further comprises a third peptide coupled to the C-terminus of the light chain of the first Fab region; wherein the first peptide comprises GCGP, or an analog or functional variant thereof, the second peptide comprises GLP-1 , or an analog or functional variant thereof, and the third peptide comprises apelin, or an analog or functional variant thereof.

34. The fusion protein of any one of claims 30-32, the fusion protein further comprising a second Fab region, wherein the first peptide is coupled to the C-terminus of the light chain of the first Fab region, the second peptide is coupled to the C-terminus of the light chain of the second Fab region, and the first peptide and the second peptide comprises apelin, or an analog or functional variant thereof.Attorney Docket No.: 064630-503001 WO35. The fusion protein of any one of claims 30-32, the fusion protein further comprising a second Fab region, wherein the first peptide is coupled to the C-terminus of the heavy chain Fab portion of the first Fab region, the second peptide is coupled to the C-terminus of the heavy chain Fab portion of the second Fab region, and the first peptide and the second peptide comprises apelin, or an analog or functional variant thereof.

36. The fusion protein of any one of claims 1 -19, further comprises a fourth peptide, the fourth peptide coupled to a fourth terminus of the antigen-binding molecule or a terminus of the first region or the second region, wherein the first peptide, the second peptide, the third peptide and the fourth peptide are coupled to different termini.

37. The fusion protein of claim 36, further comprises a fifth peptide, the fifth peptide coupled to a fifth terminus of the antigen-binding molecule or a terminus of the first region or the second region, wherein the first peptide, the second peptide, the third peptide, the fourth peptide and the fifth peptide are coupled to different termini.

38. The fusion protein of claim 37, further comprises a sixth peptide, the sixth peptide coupled to a sixth terminus of the antigen-binding molecule or a terminus of the first region or the second region, wherein the first peptide, the second peptide, the third peptide, the fourth peptide, the fifth peptide, and the sixth peptide are coupled to different termini.

39. The fusion protein of any one of claims 36-38, wherein the fourth peptide, the fifth peptide, and / or the sixth peptide comprises a peptide selected from the group consisting of: GCGP, GLP-1 , GIP, LEAP2, and analogs or functional variants thereof.

40. The fusion protein of any one of claims 1 -39, wherein at least one of the peptides is GLP-1 , and wherein the fusion protein comprises a EC50 value of less than about 5- fold, less than about 4-fold, less than about 3-fold, or less than about 2-fold of a EC50 value of a control, wherein the control is GLP-1 (1 -37).41 . The fusion protein of any one of claims 1 -39, wherein at least one of the peptides is GCGP, wherein the fusion protein comprises a EC50 value of less than about 5-fold,Attorney Docket No.: 064630-503001 WO less than about 4-fold, less than about 3-fold, or less than about 2-fold of a EC50 value of a control, wherein the control is glucagon (1 -29).

42. The fusion protein of any one of claims 1 -39, wherein at least one of the peptides is apelin, wherein the fusion protein comprises a EC50 value of less than about 5-fold, less than about 4-fold, less than about 3-fold, or less than about 2-fold of a EC50 value of a control, wherein the control is apelin 13.

43. A nucleic acid comprising nucleic acid sequences encoding the fusion protein of any one of claims 1 -42.

44. A vector comprising the nucleic acid of claim 43.

45. A cell comprising the vector of claim 44.

46. A pharmaceutical composition comprising the fusion protein of any one of claims 1 - 42, the vector of claim 44, or the cell of claim 45.

47. A method of treating a disease in a subject in need thereof, comprising administering the fusion protein of any one of clams 1 -42 or the pharmaceutical composition of claim 46 to the subject.

48. The method of claim 47, wherein the disease is a metabolic disease or a muscle wasting disease.

49. The method of claim 48, wherein the metabolic disease is obesity, Type 1 diabetes, Type 2 diabetes, metabolic syndrome, insulin resistance, obesity-related heart failure, obesity-associated pulmonary arterial hypertension, fatty liver disease, MASH, or MASLD.

50. The method of any of claims 47-49, wherein the administration results in lowered plasma glucose, reduced gastric and / or intestinal mobility, reduced gastric and / or intestinal emptying, reduced food intake, body weight loss, or any combination thereof in the subject, compared to a control subject.51 . The method of any of claims 47-49, wherein the administration results in positive inotropic effects, myocardial protection, lowered systolic blood pressure, cardiac improvement, renoprotection, reduced inflammation, muscle regeneration, muscle growth, muscle adaptation, or any combination thereof in the subject, compared to a control subject.Attorney Docket No.: 064630-503001 WO52. The method of any of claims 47-49, wherein the administration results in loss of fat mass in the subject.

53. The method of any of claims 47-49, wherein the administration results in muscle preservation or reduced muscle loss in the subject as compared to a control subject.

54. The method of claim 53, wherein the reduced muscle loss comprises less than about 90%, less than about 80%, less than about 70%, less than about 60%, less than about 50%, or less than over about 50% of a muscle loss level in a control subject about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 9 months, about 12 months, or after 12 months after the administration.

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