Antibodies targeting ActRIIA and ActRIIB

Abstract

The present disclosure relates to antibodies and antibody fragments specific to ActRIIA and ActRIIB. The antibodies are improved versions of bimagrumab. The antibodies of the present invention have improved affinity for ActRIIA—which leads to improved in vitro potency and efficacy—improved PK and PD profiles, and higher stability that makes the antibodies suitable for sc administration. Optionally, they possess an Fc variant that makes the antibodies safe for long-term treatment.

Description

Technology Field

[0001] The present disclosure relates to antibodies and antibody fragments specific to ActRIIA and ActRIIB. The antibody is an improved version of bimagrumab. The antibody of the present invention has improved affinity for ActRIIA—this is an improved in vitro ( in vitro ) leading to potency and efficacy -, improved PK and PD profiles, and higher stability that makes the antibody suitable for sc administration. Optionally, they possess Fc modifications that make the antibody safe for long-term treatment. Background Technology

[0002] Activin is a dimeric growth and differentiation factor belonging to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activin signals via a heteromeric complex of receptor serine kinases comprising at least two type I (I and IB) and two type II (II and HB, also known as ACVR2A and ACVR2B) receptors. These receptors are all transmembrane proteins composed of a ligand-binding extracellular domain with a cysteine-rich region, a transmembrane domain, and a cytoplasmic domain predicted to be serine / threonine specific. Type I receptors are essential for signaling, while type II receptors are required for ligand binding and the expression of type I receptors. Type I and type II receptors form a stable complex after ligand binding, leading to phosphorylation of type I receptors by type II receptors.

[0003] Activin receptors II A and B (ActRIIA, ActRIIB) are receptors for myostatin. Interactions between myostatin and these receptors regulate the inhibition of skeletal muscle differentiation through the Smad-dependent pathway. Therefore, skeletal muscle formation can be induced by inhibiting or preventing myostatin from binding to ActRIIA and B. Blockade of ActRII A or ActRII B alone is not sufficient to induce skeletal muscle formation (Reference [Proc Natl Acad Sci USA (2017) 114:12448-53]).

[0004] The literature [Bogdanovich et al (Nature, 2002, 420:418-421)] describes that anti-myostatin antibodies can block myostatin, leading to an increase in muscle mass in a mouse model of Duchenne muscular dystrophy. The literature [Bradley et al (Cell MoI. Life Sci. 2008, 65:2119-2124)] reviews various available approaches to modulate the myostatin / ActRIIB interaction, including the aforementioned anti-myostatin antibodies, inhibiting the release of mature myostatin by administering myostatin propeptides, blocking myostatin receptors by administering follistatin, inducing follistatin production by administering HDAC inhibitors, administering modified myostatin polypeptides that prevent myostatin from binding to receptors, and administering soluble decoy receptors for myostatin.

[0005] Bimagrumab (BYM338) is a human monoclonal antibody targeting ActRIIB, with strongly reduced binding to ActRIIB. It was isolated from a phage display library and developed for the treatment of pathological muscle loss and wasting. Bimagrumab has also been reported to be safe and effective for the treatment of excessive steatosis and metabolic disorders in adult patients with obesity and type 2 diabetes. In January 2023, it entered a Phase IIb trial for obesity. Bimagrumab is disclosed in WO2010 / 125003.

[0006] However, several characteristics of bimagrumab make this antibody unsuitable for human administration. The present invention addresses these drawbacks and provides novel and improved derivatives of bimagrumab. For example, the present invention provides an antibody that reacts with ActRIIB as well as having a high affinity for ActRIIA. At the same time, the biophysical properties of bimagrumab have been improved. The antibody of the present invention not only has less non-specific binding but also exhibits an improved HIC score, reduced charge-based interactions, and reduced viscosity. This leads to higher efficacy, as demonstrated in in vivo mouse models, improved pharmacokinetic parameters, as demonstrated in cynomolgus monkeys and minipigs, and improved formulatability.

[0007] The present invention relates to an antibody or antibody fragment specific to human ActRIIB, wherein the antibody or antibody fragment has a higher affinity for human ActRIIB than an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8. In a given embodiment, the antibody or antibody fragment has one or more of the following additional characteristics compared to an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8:

[0008] a) Less non-specific binding,

[0009] b) Improved HIC score,

[0010] c) Improved heparin score,

[0011] d) Lower IC95 in the myostatin inhibition assay,

[0012] e) Lower IC95 in the activin inhibition test, or

[0013] f) Reduced viscosity.

[0014] The present invention relates to an antibody or antibody fragment specific to human Actriib, wherein the antibody or antibody fragment is

[0015] a) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14,

[0016] b) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 17, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18,

[0017] c) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 20, and the LCDR3 region of SEQ ID NO. 14,

[0018] d) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, and the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 14,

[0019] e) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18,

[0020] f) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 26, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 27,

[0021] g) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 29, the LCDR2 region of SEQ ID NO. 30, and the LCDR3 region of SEQ ID NO. 14,

[0022] h) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 33, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 34,

[0023] i) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14,

[0024] j) includes a variable light chain comprising the HCDR1 region of sequence number 3, the HCDR2 region of sequence number 11, the HCDR3 region of sequence number 5, the LCDR1 region of sequence number 22, the LCDR2 region of sequence number 41, and the LCDR3 region of sequence number 14.

[0025] The present invention also relates to an antibody or antibody fragment specific to human Actriib, wherein the antibody or antibody fragment is

[0026] a) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14,

[0027] b) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 17, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18,

[0028] c) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 20, and the LCDR3 region of SEQ ID NO. 14,

[0029] d) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, and the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 14,

[0030] e) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18,

[0031] f) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 26, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 27,

[0032] g) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 29, the LCDR2 region of SEQ ID NO. 30, and the LCDR3 region of SEQ ID NO. 14,

[0033] h) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 33, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 34,

[0034] i) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14,

[0035] j) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 20, and the LCDR3 region of SEQ ID NO. 14,

[0036] k) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, and the LCDR1 region of SEQ NO. 22, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, or

[0037] l) Includes a variable light chain comprising the HCDR1 region of sequence number 3, the HCDR2 region of sequence number 11, the HCDR3 region of sequence number 5, the LCDR1 region of sequence number 22, the LCDR2 region of sequence number 41, and the LCDR3 region of sequence number 14.

[0038] The present invention relates to an antibody or antibody fragment specific to human Actriib, wherein the antibody or antibody fragment is

[0039] a) variable heavy chain of sequence number 12 and variable light chain of sequence number 15,

[0040] b) variable heavy chain of sequence number 16 and variable light chain of sequence number 19,

[0041] c) variable heavy chain of sequence number 16 and variable light chain of sequence number 21,

[0042] d) variable heavy chain of sequence number 16 and variable light chain of sequence number 23,

[0043] e) variable heavy chain of sequence number 24 and variable light chain of sequence number 25,

[0044] f) variable heavy chain of sequence number 16 and variable light chain of sequence number 28,

[0045] g) variable heavy chain of sequence number 16 and variable light chain of sequence number 31,

[0046] h) variable heavy chain of sequence number 32 and variable light chain of sequence number 35,

[0047] i) variable heavy chain of sequence number 36 and variable light chain of sequence number 15,

[0048] j) variable heavy chain of sequence number 37 and variable light chain of sequence number 21,

[0049] k) variable heavy chain of sequence number 37 and variable light chain of sequence number 23,

[0050] l) Variable heavy chain of sequence number 38 and variable light chain of sequence number 23,

[0051] m) Variable heavy chain of sequence number 37 and variable light chain of sequence number 39,

[0052] n) the variable heavy chain of SEQ ID NO. 37 and the variable light chain of SEQ ID NO. 40, or

[0053] o) Includes the variable heavy chain of sequence number 37 and the variable light chain of sequence number 42.

[0054] In a given embodiment, the antibody specific to human ActRIIB comprises a modification in the Fc region that increases the half-life of the antibody, and preferably, the modification is a YTE mutation (M252Y / S254T / T256E).

[0055] In a given embodiment, the antibody specific to human ActRIIB comprises a silencing modification in the Fc region. Preferably, the silencing mutation is selected from PA-LALA, PG-LALA, or AEASS mutations.

[0056] In a given embodiment, the antibody specific to human ActRIIB is conjugated or fused to an additional pharmaceutically active moiety.

[0057] In a given embodiment, the antibody specific to human ActRIIB is conjugated or fused to an additional pharmaceutically active moiety.

[0058] In a given embodiment, the present invention relates to the aforementioned antibody or antibody fragment specific to human Actriib for use in medicine. Preferably, the use in medicine is for the treatment of metabolic diseases, obesity, type 2 diabetes, or cardiovascular diseases.

[0059] In a given embodiment, the present invention relates to a nucleic acid composition comprising a nucleic acid sequence encoding the aforementioned antibody or antibody fragment or a plurality of nucleic acid sequences.

[0060] In a given embodiment, the present invention relates to a vector comprising the nucleic acid composition mentioned above.

[0061] In a given embodiment, the present invention relates to a host cell comprising the aforementioned vector or the aforementioned nucleic acid composition.

[0062] In a given embodiment, the present invention relates to a pharmaceutical composition comprising the aforementioned antibody or antibody fragment and a pharmaceutically acceptable carrier or excipient. Brief explanation of the drawing

[0063] Fig. 1 This shows a schematic overview of the experimental approach taken to achieve the ultimate goal of improving the antibody bimagrumab. Fig. 2 represents the PSR score as a measure of non-specific binding to the selected antibody of the present disclosure. Fig. 3 It shows that a specific derivative of bimagrumab exhibits reduced non-specific binding. Fig. 4It shows that certain derivatives of bimagrumab improve their heparin scores and their PSR scores, and that these improvements are correlated with PSR scores. Fig. 5 This shows the measurement results of the affinity of selected binders for ActRIIA and ActRIIB. Fig. 6 It shows that a specific derivative of bimagrumab exhibits reduced non-specific binding. Fig. 7 It shows that a specific derivative of bimagrumab has an improved HIC score. Fig. 8 It shows that a specific derivative of bimagrumab has an improved heparin score. Fig. 9 It shows the results of a specific derivative of bimagrumab in the activin binding test. Fig. 10 It shows the results of a specific derivative of bimagrumab in a myostatin binding assay. Fig. 11 Opashluffer at both 5°C and 20°C regardless of the Fc portion of the binder ( Ofaschlupfer It shows that the viscosity of ) is lower compared to bimagrumab. Fig. 12 Naive after weekly intravenous administration of isotype control, bimagrumab, or ofashluffer at dose levels of 2.5 mg / kg (A), 5 mg / kg (B), and 10 mg / kg (C). ) Shows the effect on body weight (BW) in SCID mice. Data are the mean % change in BW compared to before administration (± SEM, n=6). A summary of bar graphs on body weight change at 4 weeks (days 24 to 28) is presented in (D). Fig. 13 This shows the effects on muscle mass in naive SCID mice after weekly intravenous administration of allogeneic control, bimagrumab, or ofashluffer at dose levels of 2.5 mg / kg, 5 mg / kg, and 10 mg / kg. Data are mean BW-normalized muscle mass and are expressed as % relative to allogeneic control (+ / - SEM, n=6 to 10). Fig. 14This shows serum concentrations vs. time of ofashluffer and bimagrumab in male cynomolgus monkeys (A) and male minipigs (B) after a single intravenous (IV) or subcutaneous (SC) administration. Data range from the mean ± 2 animals per group. definition The present disclosure relates to antibodies that specifically bind to ActRIIA and / or ActRIIB, and to the use of such antibodies, particularly therapeutic use. "as used in this specification" ActRIIA " and " ACVR2A The term " refers to a human protein with UniProt ID P27037. ActRIIA has the following amino acid sequence: MGAAAKLAFAVFLISCSSGAILGRSETQECLFFNANWEKDRTNQTGVEPCYGDKDKRRHCFATWKNISGSIEIVKQGCWLDDINCYDRTDCVEKKDSPEVYFCCCEGNMCNEKFSYFPEMEMVTQPTSNP VTPKPPYYNILLYSLVPLMLIAGIVICAFWVYRHHKMAYPPVLVPTQDPGPPPPSPLLGLKPLQLLEVKARGRFGCVWKAQLLNEYVAVKIFPIQDKQSWQNEYEVYSLPGMKHENILQFIGAEKRGTS VDVDLWLITAFHEKGSLSDFLKANVVSWNELCHIAETMARGLAYLHEDIPGLKDGHKPAISHRDIKSKNVLLKNNLTACIADFGLALKFEAGKSAGDTHGQVGTRRYMAPEVLEGAINFQRDAFLRIDM YAMGLVLWELASRCTAADGPVDEYMLPFEEEIGQHPSLEDMQEVVVHKKKRPVLRDYWQKHAGMAMLCETIEECWDHDAEARLSAGCVGERITQMQRLTNITTEDIVTVVTMVTNVDFPPKESSL(sequence Number 1). "as used in this specification" ActRIIB " and " ACVR2BThe term "refers to the human protein with UniProt ID Q13705. ActRIIB has the following amino acid sequence: MTAPWVALALLWGSLCAGSGRGEAETRECIYYNANWELERTNQSGLERCEGEQDKRLHCYASWRNSSGTIELVKKGCWLDDFNCYDRQECVATEENPQVYFCCCEGNFCNERFTHLPEAGGPEVTYEP PPTAPTLLTVLAYSLLPIGGLSLIVLLAFWMYRHRKPPYGHVDIHEDPGPPPPSPLVGLKPLQLLEIKARGRFGCVWKAQLMNDFVAVKIFPLQDKQSWQSEREIFSTPGMKHENLLQFIAAEKRGSNL EVELWLITAFHDKGSLTDYLKGNIITWNELCHVAETMSRGLSYLHEDVPWCRGEGHKPSIAHRDFKSKNVLLKSDLTAVLADFGLAVRFEPGKPPGDTHGQVGTRRYMAPEVLEGAINFQRDAFLRIDM YAMGLVLWELVSRCKAADGPVDEYMLPFEEEIGQHPSLEELQEVVVHKKMRPTIKDHWLKHPGLAQLCVTIEECWDHDAEARLSAGCVEERVSLIRRSVNGTTSDCLVSLVTSVTNVDLPPKESSI(sequence Number 2). Activin receptor II A (ActRIIA) and Activin receptor II B (ActRIIB) are receptors for myostatin, activin, and bone morphogenetic protein (BMP). Interactions between myostatin and these receptors regulate the inhibition of skeletal muscle differentiation through Smad-dependent pathways. For example, it is believed that skeletal muscle formation can be induced by inhibiting or preventing myostatin from binding to ActRIIA and ActRIIB through ActRII receptor antibodies (Reference [Proc Natl Acad Sci USA (2017) 114:12448-53]). "as used in this specification" antibodiesThe term “refers to a protein comprising at least two heavy (H) chains and two light (L) chains connected to each other by disulfide bonds, which interacts with an antigen. Each heavy chain consists of a heavy chain variable region (abbreviated as VH herein) and a heavy chain constant region. The heavy chain constant region consists of three domains: CH1, CH2, and CH3. Each light chain consists of a light chain variable region (abbreviated as VL herein) and a light chain constant region. The light chain constant region consists of one domain, namely CL. The VH and VL regions may be further subdivided into a supervariable region named the complementarity determining region (CDR), interspersed with a more conserved region named the framework region (FR). Each VH and VL consists of three CDRs and four FRs arranged from the amino-terminus to the carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. Variable regions of the heavy and light chains contain binding domains that interact with antigens. The constant region of the antibody can mediate the binding of immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system. The term “antibody” includes, for example, monoclonal antibodies, human antibodies, humanized antibodies, camelized antibodies, and chimeric antibodies. Antibodies may be of any homotype (e.g., IgG, IgE, IgM, IgD, IgA, and IgY), class (e.g., IgD, IgG2, IgG3, IgG4, IgA1, and IgA2), or subclass. Both the light and heavy chains are divided into regions of structural and functional homology. As used in this specification, the term " antibody fragment"It refers to one or more parts of an antibody that possess the ability to specifically interact with an antigen (e.g., by binding, steric hindrance, or stabilization spatial distribution). Examples of binding fragments include, but are not limited to, the Fab fragment, which is a monovalent fragment consisting of VL, VH, CL, and CH1 domains; the F(ab)2 fragment, which is a divalent fragment containing two Fab fragments connected by disulfide crosslinking at a hinge region; the Fd fragment, which consists of VH and CH1 domains; the Fv fragment, which consists of VL and VH domains of a single arm of the antibody; the dAb fragment (reference [Ward et al., (1989) Nature 341:544-546]) (which consists of a VH domain); and isolated complementarity determining regions (CDRs). Additionally, although the two domains of the Fv fragment, VL and VH, are encoded by distinct genes, they may be formed using recombination methods, such that the VL and VH regions pair up to form a single protein chain that constitutes a monovalent molecule. They can be conjugated by a synthetic linker that enables their production (known as single-chain Fv (scFv); see, for example, [Bird et al., (1988) Science 242:423-426]; and [Huston et al., (1988) Proc. Natl. Acad. Sci. 85:5879-5883]). Such single-chain antibodies are also intended to be included within the term "antibody fragments." These antibody fragments are obtained using conventional techniques known to those skilled in the art, and the fragments are screened for utility in the same manner as intact antibodies. Antibody fragments can also be introduced into single-domain antibodies, maxibodi, minibodies, intrabodies, diabodies, triabodi, tetrabodies, v-NAR, and bis-scFv (see, for example, [Hollinger and Hudson, (2005) Nature Biotechnology 23:1 [Refer to 126-1 136]).The antibody fragment can be grafted into a scaffold based on a polypeptide such as fibronectin type III (Fn3) (see U.S. Patent No. 6,703,199; this patent describes a fibronectin polypeptide monobody). The antibody fragment can be introduced into a single-strand molecule comprising a pair of tandem Fv segments (VH-CH1-VH-CH1) forming a pair of antigen-binding sites together with a complementary light chain polypeptide (References [Zapata et al., (1995) Protein Eng. 8:1057-1062]; and U.S. Patent No. 5,641,870). The structure and location of immunoglobulin variable domains, e.g., CDRs, can be defined using well-known numbering systems, e.g., the Kabat numbering system, the Chothia numbering system, or a combination of Kabat and Chothia (e.g., references [Sequences of Proteins of Immunological Interest, US Department of Health and Human Services (1991), eds. Kabat et al.]; references [Lazikani et al., (1997) J. Mol. Bio. 273:927-948]; references [Kabat et al., (1991) Sequences of Proteins of Immunological Interest, 5th edit., NIH Publication no. 91-3242 US Department of Health and Human Services]; references [Chothia et al., (1987) J. Mol. Biol. 196:901-917]; See [Chothia et al., (1989) Nature 342:877-883]; and [Al-Lazikani et al., (1997) J. Mol. Biol. 273:927-948]; [Annals of the New York Academy of Sciences, 764, 47-49 (1995)]; and [Nucleic Acids Research, 25, 206-211 (1997)]). As used in this specification, " Human antibodies " or " Human antibody fragment"These are antibodies and antibody fragments having variable regions in which both the framework and CDR regions are derived from sequences of human origin. Human antibodies can also be isolated from synthetic libraries or from genetically modified mice (e.g., Xenomouse, OmniMouse, Harbour Mouse, ATX-Gx Mouse, Trianni Mouse), which provided the respective system yields of antibodies having variable regions in which both the framework and CDR regions are derived from sequences of human origin. Furthermore, if the antibody contains a constant region, the constant region is also derived from such sequences. Human origin includes, for example, human germline sequences, or mutated versions of human germline sequences, or antibodies containing consensus framework sequences derived from human framework sequence analysis as described in the literature [Knappik et al., (2000) J Mol Biol 296:57-86)]. In this specification, " Humanized antibodies " or " Humanized antibody fragment It is defined as an antibody molecule having an invariant antibody region derived from a sequence of human origin, and a variable antibody region, a part thereof, or only the CDR derived from another species. For example, a humanized antibody can be CDR-grafted, wherein the CDR of the variable domain is derived from a non-human origin, while one or more frameworks of the variable domain are of human origin, and the invariant domain (if present) is of human origin. In this specification, the term " Chimeric Antibodies " or " Chimeric antibody fragment" is defined as an antibody molecule having a constant antibody region derived from or corresponding to a sequence found in one species, and a variable antibody region derived from another species. Preferably, the constant antibody region is derived from or corresponding to a sequence found in humans, and the variable antibody region (e.g., VH, VL, CDR, or FR regions) is derived from a sequence found in non-human animals, e.g., mice, rats, rabbits, or hamsters. Term " Isolated antibodies " or " Isolated antibody fragment "Is" refers to an antibody or antibody fragment that is substantially free of other antibodies or antibody fragments having different antigen specificities. Furthermore, the isolated antibody or antibody fragment may be substantially free of other cellular material and / or chemicals. Thus, in some embodiments, the provided antibody is an isolated antibody, which is separated from an antibody having different specificities. The isolated antibody may be a monoclonal antibody. The isolated antibody may be a recombinant monoclonal antibody. However, an isolated antibody that specifically binds to an epitope, isoform, or variant of a target may have cross-reactivity to other related antigens of different species (e.g., species homologs). As used in this specification, the term " Recombinant antibody " or " Recombinant antibody fragment"It comprises all antibodies or antibody fragments that are manufactured, expressed, generated, or isolated by means not naturally occurring. Examples include antibodies isolated from host cells transformed to express antibodies, antibodies selected and isolated from a library of recombinant or combined human antibodies, antibodies manufactured, expressed, generated, or isolated by any other means involving slicing all or part of a human immunoglobulin gene sequence into other DNA sequences, or antibodies isolated from animals (e.g., mice) or hybridomas produced therefrom into which the human immunoglobulin gene has been introduced or chromosomed (e.g., mice). Preferably, such recombinant antibodies have a variable region in which the framework and CDR region are derived from the human germline immunoglobulin sequence. However, in certain embodiments, such recombinant human antibodies may undergo in vitro mutagenesis (or in vivo somatic mutagenesis when animals into which the human Ig sequence has been introduced are used), and accordingly, the amino acid sequences of the VH and VL regions of the recombinant antibody are It is a sequence derived from and related to human germline VH and VL sequences, but which may not naturally exist within the human antibody germline repertoire in vivo. Recombinant antibodies may be monoclonal antibodies. As used in this specification, the term " single clone "It has the meaning typically attributed to it in the art, namely, an antibody or antibody fragment (or equivalent functional fragment) produced from a single clone of an antibody-producing cell that recognizes a single epitope on a bound antigen. As used herein, antibodies against antigens such as human ActRIIA or ActRIIB " It specifically binds to it. ", " It specifically binds to it. ", " It is specific to it. " or " It specifically recognizes it.This means that such an antibody can distinguish between such an antigen and one or more reference antigen(s), because binding specificity is a relative rather than an absolute characteristic. For example, a standard ELISA assay or a standard flow cytometry assay may be performed. Scoring may be performed by standard chromogenicity (e.g., a secondary antibody with horseradish peroxide and tetramethylbenzidine with hydrogen peroxide) or by binding of a secondary antibody labeled with PE or other dyes or markers. The reaction in a specific well is measured, for example, by optical density (OD) at 450 nm or by mean or median fluorescence intensity (MFI) in flow cytometry. A typical background (=negative reaction) may be 0.1 OD; a typical positive reaction may be 1 OD. Background and positive reaction MFIs depend significantly on instrument settings. The difference between positive and negative can exceed tenfold. Typically, the determination of binding specificity is based on a single reference It is performed using a set of about 3 to 5 unrelated antigens, such as milk powder, BSA, and transferrin, rather than an antigen. For flow cytometry, various antigen-negative cells may be used. However, antibodies that specifically bind to an antigen may be cross-reactive to each orthologous antigen from different species (e.g., interspecies homologs). In certain embodiments, such cross-reactivity to orthologous antigens is even preferred. As used herein, when an antibody binds to a closely related antigen or the same antigen from another species, the antibody is " Cross-reactivity "Have or " Cross-reactivity "is. In this disclosure, the term is used for antibodies that are specific to ActRIIB but also bind to ActRIIA. "as used in this specification" ActRII receptor antibodyThe term "antibodies specific to ActRIIA, antibodies specific to ActRIIB, and antibodies specific to both ActRIIA and ActRIIB, that is, antibodies having cross-reactivity between ActRIIA and ActRIIB." Term " Bimagrumab " refers to an antibody also known as BYM338, disclosed in WO2010 / 125003. Bimagrumab has the following amino acid sequence. [Table 1] As used in this specification, the term " Affinity " refers to the strength of interaction between a polypeptide and its target at a single site. Within each site, the binding domain of the polypeptide interacts with its target at multiple sites through weak non-covalent bonding forces; the more interactions there are, the stronger the affinity. Term " Epitope "It comprises any proteinaceous region that is specifically recognized by an antibody or its antibody fragment or interacts with a molecule in a different way. Generally, an epitope consists of a chemically active surface group of a molecule, such as an amino acid or a carbohydrate or sugar side chain, and may generally possess specific charge properties as well as specific three-dimensional structural properties. As will be understood by those skilled in the art, substantially anything that an antibody can specifically bind to can be an epitope. Term " domain " or " Protein domain "It refers to a region of a polypeptide chain of a protein that forms a functional unit and / or independently forms a three-dimensional structure. "of the present disclosure" composition"It may be used for therapeutic or prophylactic applications. Accordingly, the present disclosure comprises a pharmaceutical composition containing an antibody or antibody fragment as disclosed herein and a pharmaceutically acceptable carrier or excipient. In a related aspect, the present disclosure provides a method for treating inflammatory diseases, autoimmune diseases, hematological malignancies, and potentially other diseases. Such a method comprises the step of administering an effective amount of a pharmaceutical composition containing an antibody or antibody fragment as described herein to a subject in need thereof. The present invention provides a therapeutic method, said therapeutic method comprising the step of administering a therapeutically effective amount of an antibody or antibody fragment as disclosed herein to a subject requiring such treatment. As used herein, " Therapeutic effective dose " or " Effective amount " refers to the amount of ActRII receptor antibody required to elicit a desired biological response. According to the present disclosure, the therapeutically effective amount is the amount of ActRII receptor antibody required to treat and / or prevent a disease. " administered " or " administration "It includes, but is not limited to, delivery of the drug in an injectable form, e.g., by intravenous, intramuscular, intradermal, or subcutaneous routes, or delivery by a mucosal route, e.g., as a nasal spray or aerosol for inhalation, or as an ingestible solution, capsule, or tablet. Preferably, administration is made by an injectable form. As used in this specification, " therapy ", " treat " or " treating"Therapeutics, etc. refer to clinical interventions intended to alter the natural course of a disease in a subject being treated, and may be performed for prevention or during a clinical pathology process. Desirable effects of treatment include, but are not limited to, prevention of the onset or recurrence of the disease, alleviation of symptoms, reduction of any direct or indirect pathological consequences of the disease, prevention of metastasis, reduction of the rate of disease progression, improvement or palliative of the disease state, and remission or improved prognosis. In some embodiments, antibodies or antibody fragments according to the present disclosure are used to delay the onset of the disease or to slow the progression of the disease. "Treatment," "to treat," or "treating" may not necessarily include prevention. " prevent " or " prevention "Refers to a reduction in the risk of acquiring or causing a disease (i.e., being exposed to a disease-causing agent, or causing at least one of the clinical symptoms of a disease that has not yet occurred in a subject who may be susceptible to the disease prior to the onset of the disease). "Prevention" also refers to a method aimed at preventing the onset of a disease or its symptoms, or delaying the onset of a disease or its symptoms. As used in this regard, " object " or " bell "is rodents, e.g., mice or rats, and primates, e.g., cynomolgus monkeys (Macaca facicularis) Macaca fascicularis )), Bengal monkey(Macaca mulatta( Macaca mulatta )), Marmoset Monkey(Calytrix Zakus( Callithrix jacchus )), or human (Homo sapiens( Homo sapiens It refers to any mammal including )). Preferably, the subject is a primate, most preferably a human. Term " Effector function"This refers to biological activity attributed to the Fc region of an antibody, which varies depending on the antibody isotype. Non-limiting examples of antibody effector functions include C1q binding and complement-dependent cytotoxicity (CDC); Fc receptor binding and antibody-dependent cell-mediated cytotoxicity (ADCC) and / or antibody-dependent cellular phagocytosis (ADCP); downregulation of cell surface receptors (e.g., B cell receptors); and direct cell activation or direct cell inhibition. " Antibody-dependent cell-mediated cytotoxicity " or " ADCC " refers to a form of cytotoxicity in which an antibody bound to an Fc receptor (FcR) present on certain cytotoxic cells (e.g., NK cells, neutrophils, and macrophages) enables these cytotoxic effector cells to specifically bind to antigen-bearing target cells and subsequently kill the target cells with cytotoxicity. NK cells, which are the primary cells mediating ADCC, express only FcyRIII, whereas monocytes express FcyRI, FcyRII, and FcyRIII. " Complement-dependent cytotoxicity " or " CDC " refers to the lysis of target cells in the presence of complement. Activation of the classical complement pathway is initiated by the binding of a first component (C1q) of the complement system to an antibody (of an appropriate subclass) of the present disclosure that is bound to its alloantigen. " Antibody-dependent phagocytosis " or " ADCP " refers to the mechanism of removal of antibody-coated target cells by internalization by phagocytes, such as macrophages or dendritic cells. As used in this specification, the term " Antibody-drug conjugate " or " ADC " refers to an antibody or antibody fragment chemically linked to a second chemical moiety, such as a therapeutic agent or cytotoxic agent. As used in this specification, the term " cytotoxic drugs"is recognized in the art, and includes daunorubicin, mitoxantrone, doxorubicin, cucurbitacin, caretosin, caretoglobocin, chlamidosin, caliceamycin, methansin, nemolubicin, cryptophycin, mensacarcin, ansamitosin, mitomycin C, geldanamycin, mekercarmycin, rebecamycin, safrasin, okylactomycin, oligomycin, actinomycin, sandramycin, hypotemycin, polyketomycin, hydroxyellipticin, thiocolchicine, methotrexate, triptolide, taltobulin, lactacistine, dolastatin, orristatin, monomethyl orristatin E (MMAE), monomethyl orristatin F (MMAF), telomestatin, tubavastatin A, combretastatin, meitansinoid, MMAD, MMAF, DM1, DM4, DTT, 16-GMB-APA-GA, 17-DMAP-GA, JW 55, Pyrrolobenzodiazepine, SN-38, Ro 5-3335, Fuwainapicin, Duocarmycin, Bafilomycin, Taxoid, Tubulicin, Ferulenol, Luciol A, Fumagiline, Hygrolidin, Glucopyricidin, Amanitin, Ansatrienine, Cinerubin, Palacidin, Paloidin, Phytospongosin, Piericidin, Poronetin, Podophyllotoxin, Gramicidin A, Sanguinarin, Synefungin, Herboxidiene, Microcholine B, Microcystin, Muscotoxin A, Tolitoxin, Trifolin A, Myoseverin, Mytoxin B, Noqueolin A, Pseudolaric acid B, scurotin A, cy-dopamine, curbulin, colchicine, apidicolin, englerin, cordycepin, apoptolidine, epotillon A, limaquinone, isatropolone, isofistularin, quinaldopeptin, ixabepylon, aeroplicinin, arginosine, agroquelin, or epotillon, including but not limited to these. An exemplary pyrrolobenzodiazepine is tesyrin. Throughout this specification, unless otherwise required by the context, the word " include ", " take " and " contain " and each of these variations, for example " Includes ", " including ", " have ", " having ", " Contains " and " Containing It will be understood that "it includes the mentioned element or integer or group of elements or integers, but does not exclude any other element or integer or group of elements or integers." As used in this specification, the term " Manipulated " or " deformed "It includes the manipulation of nucleic acids or polypeptides by synthetic means (e.g., by recombinant techniques, in vitro peptide synthesis, enzymatic or chemical bonding of peptides, or some combination of these techniques). Preferably, the antibody or antibody fragment according to the present disclosure is manipulated or modified to improve one or more properties such as antigen binding, stability, half-life, effector function, immunogenicity, safety, etc. As used in this specification, " variant "Refers to a polypeptide that differs from a reference polypeptide by one or more modifications, e.g., amino acid substitution, insertion, or deletion. Variant polypeptides typically retain most of the characteristics of the reference polypeptide, e.g., binding to a target antigen, but introduce novel additional features or characteristics, e.g., variant polypeptides have a higher affinity for the target antigen compared to the reference polypeptide." As used in this specification, the term " amino acid mutation" implies including amino acid substitutions, deletions, insertions, and modifications. Any combination of substitutions, deletions, insertions, and modifications may be made, provided that the final construct has the desired characteristic, e.g., reduced binding to the Fc receptor. Amino acid sequence deletions and insertions include N- and / or C-terminal deletions and insertions of amino acid residues. Specific amino acid mutations are amino acid substitutions. Amino acid substitutions include substitutions by non-naturally occurring amino acids or substitutions by naturally occurring amino acid derivatives of the 20 standard amino acids. Amino acid mutations may be generated using genetic or chemical methods well known in the art. Genetic methods may include site-targeted mutagenesis, PCR, gene synthesis, etc. Methods other than genetic manipulation, such as methods that alter the side chain of an amino acid residue by chemical modification, are also considered to be useful. Various designations may be used herein to refer to the same amino acid mutation. For example, substituting glycine with alanine at position 237 of the antibody Fc region is 237A, G237, G237A, or It can be displayed as Gly237Ala. As used in this specification, the term " IC50 " refers to the concentration of an antibody or antibody fragment that inhibits the response in the assay to half the level between the baseline and the maximum value. Thus, it represents the concentration of an antibody or ligand at which 50% of the maximum inhibitory effect is observed. Similarly, as used herein, the term " IC90 " and " IC95 " refers to the concentration of an antibody or antibody fragment that inhibits 90% or 95% of the maximum effect in the test, respectively. As used in this specification, the term " Ka " refers to the assembly rate of specific antibody-antigen interactions. As used in this specification, the term " Kd" refers to the dissociation rate of a specific antibody-antigen interaction. The Kd value for an antibody can be determined using methods well-established in the art. As used in this specification, the term " KD " refers to the dissociation constant of a specific antibody-antigen interaction, which is obtained from the ratio of Kd to Ka (i.e., Kd / Ka) and expressed as molar concentration. A preferred method for determining the Kd of an antibody is, preferably, by using surface plasmon resonance with a biosensor system such as the Biacore system, or by using biolayer interferometry with an Octet BLI instrument. Term " control " or " suppress " or " decrease " or " to decrease " or " Chinese " or " neutralize " refers to a reduction or cessation of any phenotypic characteristic (e.g., binding or biological activity or function), or a reduction or cessation of the incidence, degree, or possibility of such characteristic. "Inhibition," "reduction," or "neutralization" does not need to be complete as long as it is detectable using an appropriate assay. In some embodiments, "reduce," "inhibit," or "neutralize" means the ability to cause a reduction of 20% or more. In other embodiments, "reduce," "inhibit," or "neutralize" means the ability to cause a reduction of 50% or more. In yet another embodiment, "reduce," "inhibit," or "neutralize" means the ability to cause a total reduction of 75%, 85%, 90%, 95%, or more. As used in this specification, the term " antagonistic An antibody refers to an antibody or antibody fragment that interacts with an antigen to partially or completely inhibit or neutralize the biological activity or function or any other phenotypic characteristic of the target antigen. " Wild type Proteins are versions or variants of proteins as they are found in nature. The amino acid sequence of the wild-type protein, for example, the Fc region of the human IgG1 antibody, is the amino acid sequence of the protein as it exists in nature. Due to allotypic differences, more than one amino acid sequence may exist for the wild-type protein. For example, multiple allotypes of the naturally occurring human IGg1 heavy chain constant region exist (see, for example, the literature [Jeffries et al. (2009) mAbs 1:1]). " Fc area" is used to define the C-terminal region of an immunoglobulin heavy chain. The Fc region of immunoglobulin generally contains two constant domains, namely the CH2 domain and the CH3 domain. Although the boundaries of the Fc region of an IgG heavy chain may vary slightly, the human IgG heavy chain Fc region is typically defined as extending from Cys226 or Pro230 to the C-terminus of the heavy chain. However, the C-terminal lysine (Lys447) of the Fc region may or may not be present. Unless otherwise specified herein, the numbering of amino acid residues within the Fc region follows the EU numbering scheme (also referred to as the EU index) as described in the literature [Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991]. Various Fc variations are commonly used. For reference, for example, the literature [Antibodies (2020) 9: Refer to

[64] . Silencing functions include (numbered according to EU index) LALA (L234A / L235A), PA-LALA (L234A / L235A / P329A), and PG-LALA (L234A / L235A / P329G) mutations, as well as AEASS mutations (L234A / L235E / G237A / A330S / P331S). The preferred Fc variant is PA-LALA. The mutation may also be one that leads to reduced binding to FcRn, thereby reducing the in vivo half-life of the antibody. Such mutations include I253A, H310A, H435A, and H435Q. Alternatively, the mutation may also be one that leads to increased binding to FcRn, thereby increasing the in vivo half-life of the antibody.Such mutations include T250Q / M428L, M252Y / S254T / T256E(YTE), H433K / N434F, and M252Y / S254T / T256E / H433K / N434F. Embodiments of the present invention polypeptide The present disclosure relates to an antibody or antibody fragment specific to ActRIIB. In a specified embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to a polypeptide comprising the amino acid sequence of SEQ ID NO. 2. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to a polypeptide comprising the amino acid sequence of SEQ ID NO. 2. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB that is cross-reactive with ActRIIA. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to a polypeptide comprising the amino acid sequence of SEQ ID NO. 2 and cross-reactive with the polypeptide comprising the amino acid sequence of SEQ ID NO. 2. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to a polypeptide comprising the amino acid sequence of SEQ ID NO. 2 and cross-reactive with the polypeptide comprising the amino acid sequence of SEQ ID NO. 2. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB and human ActRIIA. In a predetermined embodiment, the present disclosure relates to a specific antibody or antibody fragment that is cross-reactive between human ActRIIB and human ActRIIA. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to a polypeptide comprising the amino acid sequence of SEQ ID NO. 2 and a polypeptide comprising the amino acid sequence of SEQ ID NO. 1. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to a polypeptide comprising the amino acid sequence of SEQ ID NO. 2 and a polypeptide comprising the amino acid sequence of SEQ ID NO. 1. More specifically, the antibody or antibody fragment disclosed herein is an improved derivative of bimagrumab. In a given embodiment, the present disclosure relates to an antibody or antibody fragment that is an improved derivative of an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8. Despite its clinical success, bimagrumab possesses several characteristics that can be improved. For example, improved affinity for ActRIIA can increase potency and efficacy. Reduced non-specific binding can increase PK properties as well as bioavailability following sc administration. Improvements in biophysical properties may be important for sc formulations. All these aspects aim to reduce the amount of antibody required to achieve full efficacy over an extended period, thereby enabling antibody administration for high patient compliance and lower product costs. Accordingly, in a specific embodiment, the present disclosure relates to an antibody or antibody fragment that is an improved derivative of an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8. In a specific embodiment, the present disclosure relates to an antibody or antibody fragment that is an improved derivative of an antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 9 and a variable light chain of SEQ ID NO. 10. In a given embodiment, the improvement is selected from one or more of the following characteristics: a) Higher affinity for human Actriia, b) Less non-specific binding, c) Improved HIC score, d) Improved heparin score, e) Lower IC95 in the myostatin inhibition assay, or f) Lower IC95 in the activin inhibition test. In a given embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, wherein the antibody or antibody fragment has a higher affinity for human ActRIIB than an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8. In a given embodiment, the present disclosure relates to an antibody or antibody fragment specific to human Actriib, wherein the antibody or antibody fragment has one or more of the following additional characteristics compared to an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8: a) Less non-specific binding, b) Improved HIC score, c) Improved heparin score, d) Lower IC95 in the myostatin inhibition assay, e) Lower IC95 in the activin inhibition test, or f) Reduced viscosity. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having a higher affinity for human ActRIIA compared to an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having a higher affinity for human ActRIIA compared to an antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 9 and a variable light chain of SEQ ID NO. 10. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having less non-specific binding compared to an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having less non-specific binding compared to an antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 9 and a variable light chain of SEQ ID NO. 10. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having an improved HIC score compared to an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having an improved HIC score compared to an antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 9 and a variable light chain of SEQ ID NO. 10. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having an improved heparin score compared to an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having an improved heparin score compared to an antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 9 and a variable light chain of SEQ ID NO. 10. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having a lower IC50 in a myostatin inhibition assay compared to an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having a lower IC50 in a myostatin inhibition assay compared to an antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 9 and a variable light chain of SEQ ID NO. 10. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having a lower IC90 in a myostatin inhibition assay compared to an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having a lower IC50 in a myostatin inhibition assay compared to an antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 9 and a variable light chain of SEQ ID NO. 10. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having a lower IC95 in a myostatin inhibition assay compared to an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having a lower IC50 in a myostatin inhibition assay compared to an antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 9 and a variable light chain of SEQ ID NO. 10. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having a lower IC50 in an activin inhibition test compared to an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having a lower IC50 in an activin inhibition test compared to an antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 9 and a variable light chain of SEQ ID NO. 10. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having a lower IC90 in an activin inhibition test compared to an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having a lower IC50 in an activin inhibition test compared to an antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 9 and a variable light chain of SEQ ID NO. 10. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having a lower IC95 in an activin inhibition test compared to an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment having a lower IC50 in an activin inhibition test compared to an antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 9 and a variable light chain of SEQ ID NO. 10. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or antibody fragment specific to human Actriib, wherein the antibody or antibody fragment is a) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, b) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 17, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18, c) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 20, and the LCDR3 region of SEQ ID NO. 14, d) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, and the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 14, e) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18, f) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 26, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 27, g) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 29, the LCDR2 region of SEQ ID NO. 30, and the LCDR3 region of SEQ ID NO. 14, h) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 33, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 34, i) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, j) comprises a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 41, and the LCDR3 region of SEQ ID NO. 14. In a given embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or antibody fragment specific to human Actriib, wherein the antibody or antibody fragment is a) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, b) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 17, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18, c) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 20, and the LCDR3 region of SEQ ID NO. 14, d) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, and the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 14, e) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18, f) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 26, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 27, g) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 29, the LCDR2 region of SEQ ID NO. 30, and the LCDR3 region of SEQ ID NO. 14, h) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 33, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 34, i) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, j) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 20, and the LCDR3 region of SEQ ID NO. 14, k) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, and the LCDR1 region of SEQ NO. 22, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, or l) comprises a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 41, and the LCDR3 region of SEQ ID NO. 14. In a given embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, wherein the antibody or antibody fragment comprises an HCDR1 region of SEQ ID NO. 3, an HCDR2 region of SEQ ID NO. 11, an HCDR3 region of SEQ ID NO. 5, an LCDR1 region of SEQ ID NO. 6, an LCDR2 region of SEQ ID NO. 13, and an LCDR3 region of SEQ ID NO. 14. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, wherein the antibody or antibody fragment comprises an HCDR1 region of SEQ ID NO. 3, an HCDR2 region of SEQ ID NO. 11, an HCDR3 region of SEQ ID NO. 5, an LCDR1 region of SEQ ID NO. 17, an LCDR2 region of SEQ ID NO. 13, and an LCDR3 region of SEQ ID NO. 18. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, wherein the antibody or antibody fragment comprises an HCDR1 region of SEQ ID NO. 3, an HCDR2 region of SEQ ID NO. 11, an HCDR3 region of SEQ ID NO. 5, an LCDR1 region of SEQ ID NO. 6, an LCDR2 region of SEQ ID NO. 20, and an LCDR3 region of SEQ ID NO. 14. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, wherein the antibody or antibody fragment comprises an HCDR1 region of SEQ ID NO. 3, an HCDR2 region of SEQ ID NO. 11, an HCDR3 region of SEQ ID NO. 5, an LCDR1 region of SEQ ID NO. 22, an LCDR2 region of SEQ ID NO. 13, and an LCDR3 region of SEQ ID NO. 14. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, wherein the antibody or antibody fragment comprises an HCDR1 region of SEQ ID NO. 3, an HCDR2 region of SEQ ID NO. 4, an HCDR3 region of SEQ ID NO. 5, an LCDR1 region of SEQ ID NO. 6, an LCDR2 region of SEQ ID NO. 13, and an LCDR3 region of SEQ ID NO. 18. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, wherein the antibody or antibody fragment comprises an HCDR1 region of SEQ ID NO. 3, an HCDR2 region of SEQ ID NO. 11, an HCDR3 region of SEQ ID NO. 5, an LCDR1 region of SEQ ID NO. 26, an LCDR2 region of SEQ ID NO. 13, and an LCDR3 region of SEQ ID NO. 27. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, wherein the antibody or antibody fragment comprises an HCDR1 region of SEQ ID NO. 3, an HCDR2 region of SEQ ID NO. 11, an HCDR3 region of SEQ ID NO. 5, an LCDR1 region of SEQ ID NO. 29, an LCDR2 region of SEQ ID NO. 30, and an LCDR3 region of SEQ ID NO. 14. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, wherein the antibody or antibody fragment comprises an HCDR1 region of SEQ ID NO. 3, an HCDR2 region of SEQ ID NO. 4, an HCDR3 region of SEQ ID NO. 5, an LCDR1 region of SEQ ID NO. 33, an LCDR2 region of SEQ ID NO. 13, and an LCDR3 region of SEQ ID NO. 34. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, wherein the antibody or antibody fragment comprises an HCDR1 region of SEQ ID NO. 3, an HCDR2 region of SEQ ID NO. 11, an HCDR3 region of SEQ ID NO. 5, an LCDR1 region of SEQ ID NO. 6, an LCDR2 region of SEQ ID NO. 13, and an LCDR3 region of SEQ ID NO. 14. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, wherein the antibody or antibody fragment comprises an HCDR1 region of SEQ ID NO. 3, an HCDR2 region of SEQ ID NO. 11, an HCDR3 region of SEQ ID NO. 5, an LCDR1 region of SEQ ID NO. 6, an LCDR2 region of SEQ ID NO. 20, and an LCDR3 region of SEQ ID NO. 14. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, wherein the antibody or antibody fragment comprises an HCDR1 region of SEQ ID NO. 3, an HCDR2 region of SEQ ID NO. 11, an HCDR3 region of SEQ ID NO. 5, an LCDR1 region of SEQ ID NO. 22, an LCDR2 region of SEQ ID NO. 13, and an LCDR3 region of SEQ ID NO. 14. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, wherein the antibody or antibody fragment comprises an HCDR1 region of SEQ ID NO. 3, an HCDR2 region of SEQ ID NO. 11, an HCDR3 region of SEQ ID NO. 5, an LCDR1 region of SEQ ID NO. 22, an LCDR2 region of SEQ ID NO. 41, and an LCDR3 region of SEQ ID NO. 14. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or antibody fragment specific to human Actriib, wherein the antibody or antibody fragment is a) variable heavy chain of sequence number 12 and variable light chain of sequence number 15, b) variable heavy chain of sequence number 16 and variable light chain of sequence number 19, c) variable heavy chain of sequence number 16 and variable light chain of sequence number 21, d) variable heavy chain of sequence number 16 and variable light chain of sequence number 23, e) variable heavy chain of sequence number 24 and variable light chain of sequence number 25, f) variable heavy chain of sequence number 16 and variable light chain of sequence number 28, g) variable heavy chain of sequence number 16 and variable light chain of sequence number 31, h) variable heavy chain of sequence number 32 and variable light chain of sequence number 35, i) variable heavy chain of sequence number 36 and variable light chain of sequence number 15, j) variable heavy chain of sequence number 37 and variable light chain of sequence number 21, k) variable heavy chain of sequence number 37 and variable light chain of sequence number 23, l) Variable heavy chain of sequence number 38 and variable light chain of sequence number 23, m) Variable heavy chain of sequence number 37 and variable light chain of sequence number 39, n) the variable heavy chain of SEQ ID NO. 37 and the variable light chain of SEQ ID NO. 40, or o) Includes the variable heavy chain of SEQ ID NO. 37 and the variable light chain of SEQ ID NO. 42. In a given embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 12 and a variable light chain of SEQ ID NO. 15. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 16 and a variable light chain of SEQ ID NO. 19. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 16 and a variable light chain of SEQ ID NO. 21. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 16 and a variable light chain of SEQ ID NO. 23. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 24 and a variable light chain of SEQ ID NO. 25. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 16 and a variable light chain of SEQ ID NO. 28. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 16 and a variable light chain of SEQ ID NO. 31. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 32 and a variable light chain of SEQ ID NO. 35. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 36 and a variable light chain of SEQ ID NO. 15. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 37 and a variable light chain of SEQ ID NO. 21. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 37 and a variable light chain of SEQ ID NO. 23. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 38 and a variable light chain of SEQ ID NO. 23. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 37 and a variable light chain of SEQ ID NO. 39. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or antibody fragment specific to human Actriib, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 37 and a variable light chain of SEQ ID NO. 40. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain of SEQ ID NO. 37 and a variable light chain of SEQ ID NO. 42. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising six CDRs of any one of the antibodies disclosed in Table 2, Table 7, Table 8, Table 9 or Table 12. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising six CDRs of any one of the antibodies disclosed in Table 2 or Table 12. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising six CDRs of any one of the antibodies disclosed in Table 12. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising six CDRs as defined by any one of the carbats of the antibodies disclosed in Table 12. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain and a variable light chain of any one of the antibodies disclosed in Table 2, Table 7, Table 8, Table 9 or Table 12. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain and a variable light chain of any one of the antibodies disclosed in Table 2 or Table 12. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB, said antibody or antibody fragment comprising a variable heavy chain and a variable light chain of any one of the antibodies disclosed in Table 12. In a predetermined embodiment, said antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 22; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO. 13; and f) Includes a light chain variable region CDR3 containing the amino acid sequence of sequence number 14. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA or ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 22; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO. 13; and f) Includes a light chain variable region CDR3 containing the amino acid sequence of sequence number 14. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA and ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 22; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO. 13; and f) Includes a light chain variable region CDR3 containing the amino acid sequence of sequence number 14. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 22; e) light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 13; and f) Includes a light chain variable region CDR3 having the amino acid sequence of sequence number 14. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA or ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 22; e) light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 13; and f) Includes a light chain variable region CDR3 having the amino acid sequence of sequence number 14. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA and ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 22; e) light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 13; and f) Includes a light chain variable region CDR3 having the amino acid sequence of sequence number 14. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 16 and a light chain variable region having the amino acid sequence of SEQ ID NO. 23. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA or ActRIIB, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 16 and a light chain variable region having the amino acid sequence of SEQ ID NO. 23. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA and ActRIIB, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 16 and a light chain variable region having the amino acid sequence of SEQ ID NO. 23. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 29; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ No. 30; and f) Includes a light chain variable region CDR3 containing the amino acid sequence of sequence number 14. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA or ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 29; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ No. 30; and f) Includes a light chain variable region CDR3 containing the amino acid sequence of sequence number 14. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA and ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 29; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ No. 30; and f) Includes a light chain variable region CDR3 containing the amino acid sequence of sequence number 14. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 29; e) light chain variable region CDR2 having the amino acid sequence of SEQ No. 30; and f) Includes a light chain variable region CDR3 having the amino acid sequence of sequence number 14. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA or ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 29; e) light chain variable region CDR2 having the amino acid sequence of SEQ No. 30; and f) Includes a light chain variable region CDR3 having the amino acid sequence of sequence number 14. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA and ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 29; e) light chain variable region CDR2 having the amino acid sequence of SEQ No. 30; and f) Includes a light chain variable region CDR3 having the amino acid sequence of sequence number 14. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 16 and a light chain variable region having the amino acid sequence of SEQ ID NO. 31. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA or ActRIIB, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 16 and a light chain variable region having the amino acid sequence of SEQ ID NO. 31. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA and ActRIIB, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 16 and a light chain variable region having the amino acid sequence of SEQ ID NO. 31. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 4; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 33; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO. 13; and f) Includes a light chain variable region CDR3 containing the amino acid sequence of sequence number 34. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA or ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 4; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 33; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO. 13; and f) Includes a light chain variable region CDR3 containing the amino acid sequence of sequence number 34. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRII and ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 4; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 33; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO. 13; and f) Includes a light chain variable region CDR3 containing the amino acid sequence of sequence number 34. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 4; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 33; e) light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 13; and f) Includes a light chain variable region CDR3 having the amino acid sequence of sequence number 34. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA or ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 4; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 33; e) light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 13; and f) Includes a light chain variable region CDR3 having the amino acid sequence of sequence number 34. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA and ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 4; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 33; e) light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 13; and f) Includes a light chain variable region CDR3 having the amino acid sequence of sequence number 34. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 32 and a light chain variable region having the amino acid sequence of SEQ ID NO. 35. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA or ActRIIB, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 32 and a light chain variable region having the amino acid sequence of SEQ ID NO. 35. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIA and ActRIIB, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 32 and a light chain variable region having the amino acid sequence of SEQ ID NO. 35. In a given embodiment, the present disclosure relates to an antibody or antibody fragment specific to human Actriib, wherein the antibody or antibody fragment is a monoclonal antibody or antibody fragment. In a given embodiment, the present disclosure relates to an antibody or antibody fragment specific to human Actriib, wherein the antibody or antibody fragment is a recombinant antibody or antibody fragment. In a given embodiment, the present disclosure relates to an antibody specific to human Actriib, said antibody being an IgG isotype. In a given embodiment, the present disclosure relates to an antibody specific to human Actriib, said antibody being of the IgG1 class. In a given embodiment, the present disclosure relates to an antibody specific to human Actriib, said antibody being of the human IgG1 class. In a given embodiment, the present disclosure relates to an antibody or antibody fragment specific to human Actriib, wherein the antibody or antibody fragment is an isolated antibody or antibody fragment. An antibody or antibody fragment according to the present disclosure may or may not be fused to one or more other amino acid residues, polypeptides, or moietys. Such fusion proteins may be prepared in any suitable manner, including genetic or chemical approaches. The linked moiety may contain a secretion or reader sequence, a sequence that aids in detection, expression, isolation, or purification, or, for example, a sequence that confers increased protein stability during recombinant generation. Non-limiting examples of potential moietys include beta-galactosidase, glutathione-S-transferase, luciferase, T7 polymerase fragment, secretion signal peptide, antibody or antibody fragment, toxin, cytokine, chemokine, reporter enzyme, a moiety capable of binding to a metal ion such as a poly-histidine tag, a tag suitable for detection and / or purification, a homo- or hetero-association domain, a moiety that increases the solubility of a protein, or a moiety comprising an enzymatic cleavage site. Antibodies or antibody fragments specific to ActRIIB may also be conjugated or fused to additional pharmaceutically active moiety. Each of these techniques and pharmaceutically active moiety is known to those skilled in the art. Effector function The Fc domain of immunoglobulins generally confers favorable pharmacokinetic properties of antibodies, such as an extended half-life in serum, and the ability to induce effector functions through binding to Fc receptors expressed on cells. Meanwhile, binding to Fc receptors can also lead to undesirable activation of certain cell surface receptors, which can result in unwanted cytokine release and serious side effects upon systemic administration. Accordingly, in certain therapeutic situations, it is desirable to reduce or eliminate the normal binding of the antibody to one or more or all Fc receptors of the wild-type Fc region, such as the wild-type IgG Fc region, and / or to the normal binding of complement components such as C1q, thereby reducing or eliminating the antibody's ability to induce effector function. For example, it may be desirable to reduce or eliminate binding to one or more or all Fcy receptors of the antibody's Fc region, such as FcyRI, FcyRIla, FcyRIIb, and FcyRIIIa. Effector functions may include, but are not limited to, one or more of the following: complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), cytokine secretion, immune complex-mediated antigen uptake by antigen-presenting cells, binding to NK cells, binding to macrophages, binding to monocytes, binding to polymorphonuclear cells, direct signaling inducing apoptosis, cross-linking of target-bound antibodies, dendritic cell maturation, or T cell priming. Reduced or lost binding to the Fc receptor and / or C1q of the Fc region is typically achieved by mutating the wild-type Fc region, e.g., the IgG1 Fc region, more specifically the human IgG1 Fc region, to produce a variant of the wild-type Fc region or a engineered Fc region, e.g., a variant human IgG1 Fc region. Substitutions that result in reduced binding may be useful. To reduce or lose the binding properties to the Fc receptor of the Fc region, non-conservative amino acid substitution—that is, replacing one amino acid with another amino acid having different structural and / or chemical properties—is preferred. Accordingly, in one embodiment, the antibody or antibody fragment specific to human ActRIIB according to the present disclosure comprises a variant Fc region having reduced or lost binding to the Fc receptor and / or C1q compared to the wild-type Fc region. In such an embodiment, the antibody or antibody fragment according to the present disclosure comprises a variant Fc region that reduces or loses the ability of the antibody to induce an effector function. In further embodiments, the antibody or antibody fragment according to the present disclosure does not substantially induce an effector function. In a given embodiment, the effector function is one or more selected from the group consisting of CDC, ADCC, and ADCP. In one embodiment, the effector function is ADCC. In one embodiment, the effector function is CDC. In one embodiment, the effector function is ADCP. In one embodiment, the antibody or antibody fragment according to the present disclosure does not substantially induce ADCC and / or CDC and / or ADCP. In one embodiment, the antibody or antibody fragment according to the present disclosure does not induce ADCC or ADCP in vitro. In one embodiment, a variant Fc region of an antibody or antibody fragment according to the present disclosure comprises one or more amino acid substitutions that reduce or eliminate the binding of the variant Fc region to one or more Fc receptors and / or C1q compared to a wild-type Fc region. In one embodiment, a variant Fc region of an antibody or antibody fragment according to the present disclosure comprises one or more amino acid substitutions that reduce or eliminate the ability of the antibody to induce effector function compared to a wild-type Fc region. In one embodiment, one or more amino acid substitutions may reduce the binding affinity of the variant Fc region to one or more Fc receptors and / or C1q by at least 2 times, at least 5 times, at least 10 times, at least 20 times, or even at least 50 times compared to a wild-type Fc region. In an alternative embodiment, one or more amino acid substitutions may reduce the ability of the antibody or antibody fragment according to the present disclosure to induce an effector function by at least 2 times, at least 5 times, at least 10 times, at least 20 times, or even at least 50 times compared to the wild-type Fc region. In one embodiment, the variant Fc region of the antibody or antibody fragment according to the present disclosure does not substantially bind to one or more Fc receptors and / or C1q. In one embodiment, the variant Fc region of the antibody according to the present disclosure substantially loses the ability of the antibody to induce an effector function. In one embodiment, the antibody or antibody fragment according to the present disclosure does not substantially induce an effector function. In one embodiment, the effector function is ADCC and / or ADCP and / or CDC. In one embodiment, the antibody or antibody fragment according to the present disclosure does not substantially induce an effector function, which means that the level of the induced effector function is not significantly higher than the background as measured in the absence of the antibody. In one embodiment, the Fc receptor is a human Fc receptor. In one embodiment, the Fc receptor is a Fcy receptor. In one embodiment, the Fc receptor is a human FcyRIIIa, FcyRI, FcyRIla, and / or FcyRIlb. In one embodiment, the antibody or antibody fragment according to the present disclosure comprises a variant human IgG1 Fc region comprising one or more amino acid substitutions compared to a wild-type human IgG1 Fc region. In one embodiment, such one or more amino acid substitutions reduce or eliminate the binding of the variant Fc region to the Fc receptor and / or C1q, or reduce the ability of the antibody to induce effector function compared to the wild-type Fc region. Various Fc variants are commonly used. For review, refer to the literature [Antibodies (2020) 9: 64], for example. Silencing features include (numbered according to EU index) LALA (L234A / L235A), PA-LALA (L234A / L235A / P329A) and PG-LALA (L234A / L235A / P329G) mutations, as well as AEASS mutations (L234A / L235E / G237A / A330S / P331S). In a given embodiment, the present disclosure relates to an antibody specific to human Actriib, said antibody comprising a silencing modification within the Fc region. In a given embodiment, the present disclosure relates to an antibody specific to human Actriib, wherein the antibody comprises a silencing modification within the Fc region, and the silencing modification is a LALA, PA-LALA, PG-LALA, or AEASS mutation. In a given embodiment, the present disclosure relates to an antibody specific to human Actriib, wherein the antibody comprises a silencing modification within the Fc region, and the silencing modification is a PA-LALA (L234A / L235A / P329A) modification. In a given embodiment, the present disclosure relates to an antibody specific to human Actriib, wherein the antibody comprises a silencing modification within the Fc region, and the silencing modification is a PG-LALA (L234A / L235A / P329G) modification. In a given embodiment, the present disclosure relates to an antibody specific to human Actriib, wherein the antibody comprises a silencing modification within the Fc region, and the silencing modification is an AEASS (L234A / L235E / G237A / A330S / P331S) modification. In a predetermined embodiment, the present disclosure relates to an antibody specific to human ActRIIB, said antibody having a mutation leading to reduced binding to FcRn, thereby reducing the in vivo half-life of the antibody. In a predetermined embodiment, the present disclosure relates to an antibody specific to human ActRIIB, said antibody comprising an Fc region having an I253A mutation (numbering according to EU index). In a predetermined embodiment, the present disclosure relates to an antibody specific to human ActRIIB, said antibody comprising an Fc region having an H310A mutation (numbering according to EU index). In a predetermined embodiment, the present disclosure relates to an antibody specific to human ActRIIB, said antibody comprising an Fc region having an H435A mutation (numbering according to EU index). In a predetermined embodiment, the present disclosure relates to an antibody specific to human ActRIIB, said antibody comprising an Fc region having an H435Q mutation (numbering according to EU index). In a specific embodiment, the present disclosure relates to an antibody specific to human ActRIIB, said antibody having a mutation leading to increased binding to FcRn, thereby increasing the in vivo half-life of the antibody. In a specific embodiment, the present disclosure relates to an antibody specific to human ActRIIB, said antibody containing a T250Q / M428L mutation (numbering according to EU index) in the Fc region. In a specific embodiment, the present disclosure relates to an antibody specific to human ActRIIB, said antibody containing an M252Y / S254T / T256E(YTE) mutation (numbering according to EU index) in the Fc region. In a specific embodiment, the present disclosure relates to an antibody specific to human ActRIIB, said antibody containing an H433K / N434F mutation (numbering according to EU index) in the Fc region. In a given embodiment, the present disclosure relates to an antibody specific to human Actriib, said antibody comprising the M252Y / S254T / T256E / H433K / N434F mutation (numbering according to EU index) within the Fc region. In a given embodiment, the present disclosure relates to an antibody specific to human Actriib, wherein the antibody or antibody fragment is a) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, b) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 17, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18, c) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 20, and the LCDR3 region of SEQ ID NO. 14, d) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, and the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 14, e) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18, f) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 26, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 27, g) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 29, the LCDR2 region of SEQ ID NO. 30, and the LCDR3 region of SEQ ID NO. 14, h) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 33, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 34, i) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, j) comprising a variable light chain including the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 41, and the LCDR3 region of SEQ ID NO. 14, and The antibody contains the M252Y / S254T / T256E(YTE) mutation (numbering according to the EU index) within the Fc region. In a given embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody specific to human Actriib, wherein the antibody or antibody fragment is a) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, b) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 17, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18, c) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 20, and the LCDR3 region of SEQ ID NO. 14, d) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, and the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 14, e) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18, f) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 26, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 27, g) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 29, the LCDR2 region of SEQ ID NO. 30, and the LCDR3 region of SEQ ID NO. 14, h) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 33, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 34, i) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, j) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 20, and the LCDR3 region of SEQ ID NO. 14, k) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, and the LCDR1 region of SEQ NO. 22, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, or l) comprising a variable light chain including the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 41, and the LCDR3 region of SEQ ID NO. 14, and The antibody contains the M252Y / S254T / T256E(YTE) mutation (numbering according to the EU index) within the Fc region. In a given embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody specific to human Actriib, wherein the antibody or antibody fragment is a) variable heavy chain of sequence number 12 and variable light chain of sequence number 15, b) variable heavy chain of sequence number 16 and variable light chain of sequence number 19, c) variable heavy chain of sequence number 16 and variable light chain of sequence number 21, d) variable heavy chain of sequence number 16 and variable light chain of sequence number 23, e) variable heavy chain of sequence number 24 and variable light chain of sequence number 25, f) variable heavy chain of sequence number 16 and variable light chain of sequence number 28, g) variable heavy chain of sequence number 16 and variable light chain of sequence number 31, h) variable heavy chain of sequence number 32 and variable light chain of sequence number 35, i) variable heavy chain of sequence number 36 and variable light chain of sequence number 15, j) variable heavy chain of sequence number 37 and variable light chain of sequence number 21, k) variable heavy chain of sequence number 37 and variable light chain of sequence number 23, l) Variable heavy chain of sequence number 38 and variable light chain of sequence number 23, m) Variable heavy chain of sequence number 37 and variable light chain of sequence number 39, n) the variable heavy chain of SEQ ID NO. 37 and the variable light chain of SEQ ID NO. 40, or o) Variable heavy chain of sequence number 37 and variable light chain of sequence number 42, The antibody contains the M252Y / S254T / T256E(YTE) mutation (numbering according to the EU index) within the Fc region. In a given embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. nucleic acids In one embodiment, the present disclosure relates to a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding an antibody or antibody fragment specific to the human Actriib of the present disclosure. In one embodiment, the present disclosure relates to a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding an antibody or antibody fragment specific to human Actriib of the present disclosure, wherein the antibody or antibody fragment a) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, b) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 17, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18, c) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 20, and the LCDR3 region of SEQ ID NO. 14, d) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, and the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 14, e) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18, f) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 26, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 27, g) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 29, the LCDR2 region of SEQ ID NO. 30, and the LCDR3 region of SEQ ID NO. 14, h) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 33, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 34, i) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, j) comprises a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 41, and the LCDR3 region of SEQ ID NO. 14. In a given embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In another embodiment, the present disclosure relates to a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding an antibody or antibody fragment specific to human Actriib of the present disclosure, wherein the antibody or antibody fragment a) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, b) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 17, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18, c) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 20, and the LCDR3 region of SEQ ID NO. 14, d) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, and the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 14, e) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18, f) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 26, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 27, g) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 29, the LCDR2 region of SEQ ID NO. 30, and the LCDR3 region of SEQ ID NO. 14, h) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 33, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 34, i) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, the LCDR1 region of SEQ NO. 6, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, j) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 20, and the LCDR3 region of SEQ ID NO. 14, k) a variable light chain comprising the HCDR1 region of SEQ NO. 3, the HCDR2 region of SEQ NO. 11, the HCDR3 region of SEQ NO. 5, and the LCDR1 region of SEQ NO. 22, the LCDR2 region of SEQ NO. 13, and the LCDR3 region of SEQ NO. 14, or l) comprises a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 41, and the LCDR3 region of SEQ ID NO. 14. In a given embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In one embodiment, the present disclosure relates to a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding an antibody or antibody fragment specific to human Actriib of the present disclosure, wherein the antibody or antibody fragment a) variable heavy chain of sequence number 12 and variable light chain of sequence number 15, b) variable heavy chain of sequence number 16 and variable light chain of sequence number 19, c) variable heavy chain of sequence number 16 and variable light chain of sequence number 21, d) variable heavy chain of sequence number 16 and variable light chain of sequence number 23, e) variable heavy chain of sequence number 24 and variable light chain of sequence number 25, f) variable heavy chain of sequence number 16 and variable light chain of sequence number 28, g) variable heavy chain of sequence number 16 and variable light chain of sequence number 31, h) variable heavy chain of sequence number 32 and variable light chain of sequence number 35, i) variable heavy chain of sequence number 36 and variable light chain of sequence number 15, j) variable heavy chain of sequence number 37 and variable light chain of sequence number 21, k) variable heavy chain of sequence number 37 and variable light chain of sequence number 23, l) Variable heavy chain of sequence number 38 and variable light chain of sequence number 23, m) Variable heavy chain of sequence number 37 and variable light chain of sequence number 39, n) the variable heavy chain of SEQ ID NO. 37 and the variable light chain of SEQ ID NO. 40, or o) Includes the variable heavy chain of SEQ ID NO. 37 and the variable light chain of SEQ ID NO. 42. In a given embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In one embodiment, the present disclosure relates to a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding an antibody or antibody fragment specific to human ActRIIB of the present disclosure, wherein the antibody or antibody fragment comprises six CDRs of any one of the antibodies disclosed in Table 2, Table 7, Table 8, Table 9 or Table 12. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In one embodiment, the present disclosure relates to a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding an antibody or antibody fragment specific to human ActRIIB of the present disclosure, wherein the antibody or antibody fragment comprises six CDRs of any one of the antibodies disclosed in Table 2 or Table 12. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In one embodiment, the present disclosure relates to a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding an antibody or antibody fragment specific to human ActRIIB of the present disclosure, wherein the antibody or antibody fragment comprises six CDRs of any one of the antibodies disclosed in Table 12. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In one embodiment, the present disclosure relates to a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding an antibody or antibody fragment specific to human ActRIIB of the present disclosure, wherein the antibody or antibody fragment comprises six CDRs as defined by any one of the antibodies disclosed in Table 12. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In one embodiment, the present disclosure relates to a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding an antibody or antibody fragment specific to human ActRIIB of the present disclosure, wherein the antibody or antibody fragment comprises a variable heavy chain and a variable light chain of one of the antibodies disclosed in Table 2, Table 7, Table 8, Table 9 or Table 12. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In one embodiment, the present disclosure relates to a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding an antibody or antibody fragment specific to human ActRIIB of the present disclosure, wherein the antibody or antibody fragment comprises a variable heavy chain and a variable light chain of one of the antibodies disclosed in Table 2 or Table 12. In one embodiment, the present disclosure relates to a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding an antibody or antibody fragment specific to human ActRIIB of the present disclosure, wherein the antibody or antibody fragment comprises a variable heavy chain and a variable light chain of one of the antibodies disclosed in Table 12. In one embodiment, the nucleic acid composition and / or the nucleic acid sequence and / or the plurality of nucleic acid sequences are isolated. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 22; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO. 13; and f) comprising a light chain variable region CDR3 containing the amino acid sequence of SEQ ID NO. 14, and The Fc region of the antibody or antigen-binding fragment contains a mutation that increases the half-life. In a specific embodiment, the mutation that increases the half-life is a YTE (M252Y / S254T / T256E) mutation. In a specific embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 22; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO. 13; and f) comprising a light chain variable region CDR3 containing the amino acid sequence of SEQ ID NO. 14, and The antibody or antigen-binding fragment comprises a silencing modification within the Fc region, wherein the silencing modification is a PA-LALA, PG-LALA, or AEASS mutation. In a given embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 22; e) light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 13; and f) comprising a light chain variable region CDR3 having the amino acid sequence of SEQ ID NO. 14, and The Fc region of the antibody or antigen-binding fragment contains a mutation that increases the half-life. In a specific embodiment, the mutation that increases the half-life is a YTE (M252Y / S254T / T256E) mutation. In a specific embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 22; e) light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 13; and f) comprising a light chain variable region CDR3 having the amino acid sequence of SEQ ID NO. 14, and The antibody or antigen-binding fragment comprises a silencing modification within the Fc region, wherein the silencing modification is a PA-LALA, PG-LALA, or AEASS mutation. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or its antigen-binding fragment that binds to ActRIIB, wherein the antibody or its antigen-binding fragment comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 16 and a light chain variable region having the amino acid sequence of SEQ ID NO. 23, and the Fc region of the antibody or antigen-binding fragment comprises a mutation that increases the half-life. In a predetermined embodiment, the mutation that increases the half-life is a YTE (M252Y / S254T / T256E) mutation. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 16 and a light chain variable region having the amino acid sequence of SEQ ID NO. 23, and the antibody or the antigen-binding fragment comprises a silencing modification within the Fc region, wherein the silencing modification is a PA-LALA, PG-LALA, or AEASS mutation. In a predetermined embodiment, the antibody or the antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 29; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ No. 30; and f) comprising a light chain variable region CDR3 containing the amino acid sequence of SEQ ID NO. 14, and The Fc region of the antibody or antigen-binding fragment contains a mutation that increases the half-life. In a specific embodiment, the mutation that increases the half-life is a YTE (M252Y / S254T / T256E) mutation. In a specific embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 29; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ No. 30; and f) comprising a light chain variable region CDR3 containing the amino acid sequence of SEQ ID NO. 14, and The antibody or antigen-binding fragment comprises a silencing modification within the Fc region, wherein the silencing modification is a PA-LALA, PG-LALA, or AEASS mutation. In a given embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 29; e) light chain variable region CDR2 having the amino acid sequence of SEQ No. 30; and f) comprising a light chain variable region CDR3 having the amino acid sequence of SEQ ID NO. 14, and The Fc region of the antibody or antigen-binding fragment contains a mutation that increases the half-life. In a specific embodiment, the mutation that increases the half-life is a YTE (M252Y / S254T / T256E) mutation. In a specific embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 11; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 29; e) light chain variable region CDR2 having the amino acid sequence of SEQ No. 30; and f) comprising a light chain variable region CDR3 having the amino acid sequence of SEQ ID NO. 14, and The antibody or antigen-binding fragment comprises a silencing modification within the Fc region, wherein the silencing modification is a PA-LALA, PG-LALA, or AEASS mutation. In a given embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 16 and a light chain variable region having the amino acid sequence of SEQ ID NO. 31, and the Fc region of the antibody or the antigen-binding fragment comprises a mutation that increases the half-life. In a predetermined embodiment, the mutation that increases the half-life is a YTE (M252Y / S254T / T256E) mutation. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 16 and a light chain variable region having the amino acid sequence of SEQ ID NO. 31, and the antibody or the antigen-binding fragment comprises a silencing modification within the Fc region, wherein the silencing modification is a PA-LALA, PG-LALA, or AEASS mutation. In a predetermined embodiment, the antibody or the antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 4; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 33; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO. 13; and f) comprising a light chain variable region CDR3 containing the amino acid sequence of SEQ ID NO. 34, and The Fc region of the antibody or antigen-binding fragment contains a mutation that increases the half-life. In a specific embodiment, the mutation that increases the half-life is a YTE (M252Y / S254T / T256E) mutation. In a specific embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 containing the amino acid sequence of SEQ ID NO. 3; b) Heavy chain variable region CDR2 containing the amino acid sequence of sequence number 4; c) Heavy chain variable region CDR3 containing the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 containing the amino acid sequence of sequence number 33; e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO. 13; and f) comprising a light chain variable region CDR3 containing the amino acid sequence of SEQ ID NO. 34, and The antibody or antigen-binding fragment comprises a silencing modification within the Fc region, wherein the silencing modification is a PA-LALA, PG-LALA, or AEASS mutation. In a given embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 4; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 33; e) light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 13; and f) comprising a light chain variable region CDR3 having the amino acid sequence of SEQ ID NO. 34, and The Fc region of the antibody or antigen-binding fragment contains a mutation that increases the half-life. In a specific embodiment, the mutation that increases the half-life is a YTE (M252Y / S254T / T256E) mutation. In a specific embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a given embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof a) Heavy chain variable region CDR1 having the amino acid sequence of sequence number 3; b) Heavy chain variable region CDR2 having the amino acid sequence of sequence number 4; c) Heavy chain variable region CDR3 having the amino acid sequence of sequence number 5; d) Light chain variable region CDR1 having the amino acid sequence of sequence number 33; e) light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 13; and f) comprising a light chain variable region CDR3 having the amino acid sequence of SEQ ID NO. 34, and The antibody or antigen-binding fragment comprises a silencing modification within the Fc region, wherein the silencing modification is a PA-LALA, PG-LALA, or AEASS mutation. In a given embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 32 and a light chain variable region having the amino acid sequence of SEQ ID NO. 35, and the Fc region of the antibody or the antigen-binding fragment comprises a mutation that increases the half-life. In a predetermined embodiment, the mutation that increases the half-life is a YTE (M252Y / S254T / T256E) mutation. In a predetermined embodiment, the antibody or antibody fragment binds to human ActRIIA and human ActRIIB. In a predetermined embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that binds to ActRIIB, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO. 32 and a light chain variable region having the amino acid sequence of SEQ ID NO. 35, and the antibody or the antigen-binding fragment comprises a silencing modification within the Fc region, wherein the silencing modification is a PA-LALA, PG-LALA, or AEASS mutation. In a predetermined embodiment, the antibody or the antibody fragment binds to human ActRIIA and human ActRIIB. vector In one embodiment, the present disclosure provides a vector comprising a nucleic acid composition comprising a nucleic acid sequence encoding an antibody or antibody fragment specific to human ActRIIB according to the present disclosure or a plurality of nucleic acid sequences, or a vector composition comprising a plurality of vectors. In one embodiment, the present disclosure provides a vector comprising a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding any one of the human ActRIIB-specific antibodies or antibody fragments disclosed in Tables 2, 7, 8, 9, or 12, or a vector composition comprising a plurality of vectors. In one embodiment, the present disclosure provides a vector comprising a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding any one of the human ActRIIB-specific antibodies or antibody fragments disclosed in Table 2 or Table 12, or a vector composition comprising a plurality of vectors. In one embodiment, the present disclosure provides a vector comprising a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding any one of the human ActRIIB-specific antibodies or antibody fragments disclosed in Table 12, or a vector composition comprising a plurality of vectors. host cell In one embodiment, the present disclosure provides a host cell comprising a vector comprising a nucleic acid composition comprising a nucleic acid sequence encoding an antibody or antibody fragment specific to human ActRIIB according to the present disclosure or a plurality of nucleic acid sequences, or a vector composition comprising a plurality of vectors. In one embodiment, the present disclosure relates to a host cell comprising a vector or a vector composition comprising a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding any one of the human ActRIIB-specific antibodies or antibody fragments disclosed in Tables 2, 7, 8, 9 or 12. In one embodiment, the present disclosure relates to a host cell comprising a vector comprising a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding any one of the human ActRIIB-specific antibodies or antibody fragments disclosed in Table 2 or Table 12, or a vector composition comprising a plurality of vectors. In one embodiment, the present disclosure relates to a host cell comprising a vector comprising a nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding any one of the human ActRIIB-specific antibodies or antibody fragments disclosed in Table 12, or a vector composition comprising a plurality of vectors. In one embodiment, a host cell according to the present disclosure may express an antibody or antibody fragment specific to human ActRIIB encoded by a vector composition or a nucleic acid composition. In an additional embodiment, the host cell is an isolated host cell. In an additional embodiment, the host cell is a mammalian cell. In one embodiment, the mammalian cell is a human cell. In another embodiment, the mammalian cell is a CHO cell. In one embodiment, the cell is an HEK cell. In another embodiment, the cell is a PERC.6 cell. In one embodiment, the cell is an HKB11 cell. Those skilled in the art will recognize that a nucleic acid sequence or a plurality of nucleic acid sequences encoding the heavy chain and / or light chain of the antibody or antibody fragment of the present disclosure may be cloned into different vectors or into the same vector.The vector may be introduced into a suitable host cell, such as a prokaryotic (e.g., bacterium) or eukaryotic (e.g., yeast or mammalian) cell, by methods well known in the art (see, for example, “Current Protocol in Molecular Biology”, Ausubel et al. (eds.), Greene Publishing Assoc and John Wiley Interscience, New York, 1989 and 1992). Numerous cloning vectors are known to those skilled in the art, and the selection of a suitable cloning vector is at the discretion of those skilled in the art. The gene may be placed under the control of a promoter, a ribosome binding site (for bacterial expression), and optionally an operator (collectively referred to herein as “control” elements), so that a nucleic acid sequence encoding the desired protein is transcribed into RNA in a host cell transformed by a vector containing such an expression construct. The coding sequence may or may not contain a signal peptide or a leader sequence. Upon expression in a host cell, the antibody or antibody fragment of the present disclosure is obtained. These steps may be achieved in various ways as known to those skilled in the art. Generally, such steps typically include the step of transforming or transfecting a host cell suitable for a nucleic acid composition or vector composition encoding an antibody or antibody fragment, or an infectious particle. Additionally, such steps typically include the step of culturing the host cell under conditions suitable for proliferation (proliferation, growth) of said host cell and the step of culturing under conditions suitable for the production (expression, synthesis) of the encoded antibody or antibody fragment. Culturing the host cell under conditions suitable for proliferation or expression is typically achieved in the presence of a medium containing components suitable for inducing cell growth or expression.In certain embodiments, the method for generating an antibody or antibody fragment of the present disclosure further comprises the step of isolating and purifying the antibody or antibody fragment generated from a host cell or medium. If the expression system secretes a protein into the growth medium, the protein may be purified directly from the medium. If no protein is secreted, it is isolated from the cell lysate or recovered from the cell membrane fraction. The selection of appropriate growth conditions and recovery methods is within the scope of the art. Subsequently, the antibody or antibody fragment of the present disclosure may be purified by a number of techniques as known to those skilled in the art. In one embodiment, the present disclosure relates to a method for generating an antibody or antibody fragment specific to human ActRIIB of any antibody disclosed in Tables 2, 7, 8, 9 or 12. In one embodiment, a method for generating an antibody or antibody fragment according to the present disclosure is provided, the method comprising the steps of: culturing a host cell comprising a vector comprising a nucleic acid composition comprising a nucleic acid sequence encoding an antibody or antibody fragment according to the present disclosure or a plurality of nucleic acid sequences, or a vector composition comprising a plurality of vectors, under conditions suitable for the expression of the antibody or antibody fragment; and isolating the antibody or antibody fragment from the host cell or host cell culture medium. As described herein, the isolated antibody or antibody fragment may be purified by techniques known in the art, such as high-performance liquid chromatography (HPLC), ion exchange chromatography, gel electrophoresis, affinity chromatography, size exclusion chromatography, etc. The conditions used to purify a specific antibody or antibody fragment will depend, in part, on factors such as net charge, hydrophobicity, hydrophilicity, etc., and will be obvious to those skilled in the art. For affinity chromatographic purification, an antibody, ligand, receptor, or antigen to which the antibody or antibody fragment binds may be used. For example, for affinity chromatographic purification of an antibody or antibody fragment according to the present disclosure, a matrix having protein A or protein G may be used. The purity of the antibody or antibody fragment may be determined by any of various well-known analytical methods, including gel electrophoresis, high-pressure liquid chromatography, etc. Treatment methods The antibodies and antibody fragments of the present disclosure, or pharmaceutical compositions containing the same, may be used for the treatment of various diseases. Accordingly, in a specific embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB for use in medicine. In another embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB for use in the treatment of a disease or disorder. The antibodies and antibody fragments of the present disclosure, or pharmaceutical compositions containing them, may be used for metabolic diseases. They increase energy expenditure to reduce fat body mass while preserving lean body mass. Antibodies and antibody fragments are also ideal combination partners with weight loss agents, such as incretins, for example, in the treatment of obesity and type 2 diabetes (Reference [Obesity (Silver Spring) (2021) 29:500-511]). The positive effects of antibodies and antibody fragments are not limited to skeletal muscle. Therefore, they can also be used therapeutically for the myocardium, cardiovascular system, and other comorbidities associated with obesity. Accordingly, in a given embodiment, the present disclosure relates to an antibody or antibody fragment specific to human ActRIIB for use in the treatment of a disease or disorder, said disease or disorder being a metabolic disease, obesity, type 2 diabetes or cardiovascular disease. In a specified embodiment, the present disclosure relates to the use of the antibody or antibody fragment of the present disclosure for the treatment of a disease associated with the unwanted presence of ActRIIB. In a specified embodiment, the present disclosure relates to the use of the antibody or antibody fragment of the present disclosure for the treatment of a disease associated with the unwanted presence of ActRIIB-positive cells. In one embodiment, the present disclosure provides a method for treating a disease. In one embodiment, the present disclosure provides a method for treating a disease, the method comprising the step of administering an antibody or antibody fragment of the present disclosure to a patient. In one embodiment, the present disclosure provides a method for treating a disease, the method comprising the step of administering an antibody or antibody fragment of the present disclosure to a subject in need thereof. In one embodiment, the present disclosure provides a method for preventing disease. In one embodiment, the present disclosure provides a method for preventing a disease, the method comprising the step of administering an antibody or antibody fragment of the present disclosure to a subject. In one embodiment, the present disclosure provides an antibody or antibody fragment according to the present disclosure for the treatment of a disease. In one embodiment, the present disclosure provides an antibody or antibody fragment according to the present disclosure for use in the treatment of a disease. In one embodiment, the present disclosure provides an antibody or antibody fragment according to the present disclosure for use in the treatment of a disease in a subject requiring treatment of a disease. In one embodiment, the present disclosure provides a use of an antibody or antibody fragment according to the present disclosure for the manufacture of a drug. In one embodiment, the present disclosure provides an antibody or antibody fragment according to the present disclosure for use as a drug. In one embodiment, the present disclosure provides an antibody or antibody fragment according to the present disclosure for use in medicine. In one embodiment, the present disclosure provides an antibody or antibody fragment according to the present disclosure for use as a drug for the treatment of a subject in need of treatment. In one embodiment, the present disclosure provides an antibody or antibody fragment specific to human Actriib according to the present disclosure for use in a method for treating a subject having a disease, said method comprising the step of administering a therapeutically effective amount of the antibody or antibody fragment according to the present disclosure to the subject. In one embodiment, the present disclosure provides a method for treating an ActRIIA or ActRIIB-mediated disease or disorder in a subject requiring treatment, the method comprising the step of administering an antibody or antibody fragment according to the present disclosure to the subject. In a predetermined embodiment, the ActRIIA or ActRIIB-mediated disease or disorder is a metabolic disease. In a predetermined embodiment, the ActRIIA or ActRIIB-mediated disease or disorder is obesity or type 2 diabetes. In a predetermined embodiment, the ActRIIA or ActRIIB-mediated disease or disorder is a cardiovascular disease. In one embodiment, the method further comprises the step of administering at least one additional therapeutically effective amount of a therapeutic agent to a subject. The subject requiring treatment is typically a mammal, more specifically a human. For use in the therapeutic method, the antibody or antibody fragment according to the present disclosure will be formulated, dosed, and administered in a manner consistent with best medical practice guidelines. Pharmaceutical composition In one embodiment, the present disclosure provides a pharmaceutical composition comprising an antibody or antibody fragment according to the present disclosure and a pharmaceutically acceptable carrier or excipient. Antibodies are administered in an effective regime, which refers to the dosage, route of administration, and frequency of administration that achieve the intended purpose, such as the reduction of endogenous HSPCs, tissue-resident or circulating immune cells, or cancer cells expressing ActRIIB. In some cases, efficacy may be observed in individual patients compared to a past control group or the past experience of the same patient. In other cases, efficacy may be demonstrated through preclinical or clinical trials in a treated patient group compared to an untreated control group. The pharmaceutical composition may further comprise at least one other pharmaceutically active compound. The pharmaceutical composition according to the present disclosure may be used for the diagnosis, prevention, and / or treatment of diseases associated with the unwanted presence of ActRIIB. The pharmaceutical composition according to the present disclosure may be used for the diagnosis, prevention, and / or treatment of diseases associated with the unwanted presence of ActRIIB-positive cells. Specifically, the present disclosure provides a pharmaceutical composition comprising an antibody or antibody fragment according to the present disclosure suitable for prophylactic, therapeutic, and / or diagnostic use in mammals, more specifically in humans. Generally, the antibody or antibody fragment according to the present disclosure may be formulated into a pharmaceutical composition comprising at least one antibody or antibody fragment according to the present disclosure, at least one pharmaceutically acceptable carrier or excipient, and optionally one or more additional pharmaceutically active compounds. Such a composition may be suitable for oral, parenteral, topical administration, or administration by inhalation. Accordingly, a pharmaceutical composition comprising at least one antibody or antibody fragment according to the present disclosure may be administered parenterally, for example, intravenously, or intramuscularly, or subcutaneously. Alternatively, the antibody of the present invention may be administered via a non-parenteral route, for example, orally or topically. In a preferred embodiment, a pharmaceutical composition comprising the antibody or antibody fragment according to the present disclosure is administered intravenously or subcutaneously. Improving efficacy and the PK profile enables the maintenance of effective antibody concentrations over the long term. This reduces the therapeutic dose required per application and, additionally, allows for a reduced frequency of drug administration. Both aspects significantly improve patient compliance and reduce product costs while ensuring sustained therapeutic effects, keeping costs for patients and the healthcare system within a reasonable range. Specifically, the antibody or antibody fragment according to the present disclosure may be used in combination with one or more pharmaceutically active compounds that are or may be used for the prevention and / or treatment of a disease involving a target antigen of interest, and as a result, a synergistic effect may or may not be obtained. Examples of such compounds, as well as routes, methods, and pharmaceutical formulations or compositions for administering them, will be apparent to clinicians. In one embodiment, the present disclosure provides a pharmaceutical composition comprising an antibody or antibody fragment according to the present disclosure for use in the prevention and / or treatment of diseases associated with the unwanted presence of ActRIIB. In one embodiment, the present disclosure provides a pharmaceutical composition comprising an antibody or antibody fragment according to the present disclosure for use in the prevention and / or treatment of diseases associated with the unwanted presence of ActRIIB-positive cells. In one embodiment, the present disclosure provides a pharmaceutical composition comprising an antibody or antibody fragment according to the present disclosure for use as a pharmaceutical agent. In one embodiment, the present disclosure provides a pharmaceutical composition comprising an antibody or antibody fragment according to the present disclosure for use in the prevention and / or treatment of metabolic diseases, obesity, type 2 diabetes, or cardiovascular diseases. In one embodiment, the present disclosure provides a method for treating a subject requiring treatment for a metabolic disease, obesity, type 2 diabetes, or cardiovascular disease by using a pharmaceutical composition comprising an antibody or antibody fragment according to the present disclosure. A method for generating an antibody or antibody fragment according to the present disclosure in a form suitable for in vivo administration is further provided, wherein the method comprises (a) obtaining an antibody or antibody fragment by a method according to the present disclosure, and (b) formulating said antibody or antibody fragment using at least one pharmaceutically acceptable carrier or excipient, thereby formulating a preparation of the antibody or antibody fragment for in vivo administration. A pharmaceutical composition according to the present disclosure comprises a therapeutically effective amount of one or more antibodies or antibody fragments according to the present disclosure dissolved in a pharmaceutically acceptable carrier or excipient. Diagnostic use In one embodiment, the present disclosure provides a use of an antibody or antibody fragment specific to human ActRIIB according to the present disclosure for the diagnosis of a disease. In one embodiment, the present disclosure provides a use of an antibody or antibody fragment according to the present disclosure for the detection of human ActRIIB. In one embodiment, the present disclosure provides a method for detecting human ActRIIB in a subject or sample, the method comprising the step of contacting said subject or sample with an antibody or antibody fragment specific to human ActRIIB according to the present disclosure. In one embodiment, the present disclosure provides a method for diagnosing a disease in a subject, the method comprising the step of contacting said subject or sample with an antibody or antibody fragment according to the present disclosure. The antibody may also be used to determine the level of ActRIIB expression in patient-derived cells. The level of ActRIIB expression may serve as a therapeutic biomarker, for example, for patient stratification. Examples Example 1: Object of the present invention The overall objective of the present invention is to provide an improved version of the antibody bimagrumab. The antibody to be produced possesses one or more of the following characteristics: improved efficacy against ActRIIA and ActRIIB, improved PK and PD profiles, and / or higher stability, thereby making the antibody suitable for sc administration. Optionally, they possess an Fc variant that makes the antibody safe for long-term treatment. Attempts were made to achieve this objective through various approaches. In order to optimize affinity and reduce non-specific binding, ultimately leading to increased efficacy and improved PD and PK, computer simulations ( in silicoOptimization of CDR was utilized via an AI-guided method. Due to higher efficacy, lower doses for treatment are possible. Biophysical properties were improved by optimizing framework regions through germline switching. Finally, Fc manipulation was tested with the aim of improving FcRn binding and silencing FcRγ binding, which would likewise improve PK and PD and reduce immune activation. Figure 1 shows a schematic overview of the parallel approaches taken. Example 2: General experimental procedure Example 2.1: Determination of the melting temperature of immunoglobulin The melting temperature of immunoglobulin was measured according to standard procedures using differential scanning fluorescence (DSF). Example 2.2: Determination of the hydrophobic profile of immunoglobulin by hydrophobic interaction chromatography Molecules were characterized by hydrophobic interaction chromatography using an Agilent 1260 infinity II system. Elution was performed through an Agilent bio HIC column (4.6 * 100 mm, 3.5 µm) using a linear gradient starting from 60% mobile phase A (50 mM sodium phosphate buffer, pH 7 + 2 M ammonium sulfate) at a flow rate of 1 mL / min to 100% mobile phase B (50 mM sodium phosphate buffer, pH 7). The eluted proteins were detected at an absorbance of 280 nm. Example 2.3: Determination of Charge-Based Interactions of Immunoglobulins by Heparin Chromatography The charge-based interaction profiles of the candidate substances were determined by heparin chromatography. Analysis was performed using an Agilent 1260 infinity II system with a TSK-GEL heparin-5 PW column (5.0 cm x 5.0 cm, 10 µm). Molecules were eluted via a linear gradient starting from 100% mobile phase A (50 mM Tris, pH 7.4) to 100% mobile phase B (50 mM Tris, 1 M NaCl, pH 7.4) at a flow rate of 0.35 mL / min. The absorption wavelength for detection was set to 280 nm. Example 2.4: Determination of Immunoglobulin Affinity for ActRIIA and ActRIIB The affinity interaction profile of the immunoglobulin was determined using an immuno-based assay called MSD-SET (Meso Scale Discovery (MSD) Solution Equilibrium Titration). In this assay, antigens (ActR2A or ActR2B) were coated onto MSD 96-well detection plates. SET plates were prepared by mixing a constant concentration of immunoglobulin with the titrated antigen and incubating overnight at 4°C to reach equilibrium. After blocking the MSD plates, 50 μl of sample solution (SET plates) containing the immunoglobulin-antigen mixture was transferred to the antigen-coated detection MSD plates. These samples were then incubated for 20 minutes to allow any free antibody to bind without significantly shifting the equilibrium. To detect the bound antibodies on the plates, the detection antibody, a Sulfo-TAG-labeled anti-human antibody (goat) (PN: R32AJ-5), was added. Next, a read buffer was added, and the ECL readings were detected by measuring electrochemiluminescence (ECL) using an MSD instrument (Sector S 600 MM). Data analysis was performed on GraphPad Prism using the equations for IgG or Fab from the literature [Journal of Biomolecular Screening 2015, Vol. 20(10) 1256-1267]. Example 2.5: Myostatin Inhibition (SMAD RGA Test) To evaluate the efficacy and potency of the inhibition of ActRIIA and ActRIIB, candidate substances were characterized in a myostatin-stimulated SMAD RGA (reporter gene assay). TGFB / SMAD signaling pathway SBE reporter HEK293 cells (BPS BioScience) were washed with PBS, separated using 0.05% trypsin, and seeded into 96-well white flat-bottom plates at 35,000 cells / well with 100 µL of medium (MEM medium, 10% FBS, 1% NEAA, 1 mM sodium pyruvate, 1% Pen / Strep). The next day, the medium was replaced with 90 µL of assay medium (MEM medium, 0.5% FBS, 1% NEAA, 1 mM sodium pyruvate, 1% Pen / Strep) containing diluted antibodies of interest (10 to 0.00015 μg / mL) or controls. Cells were incubated at 37°C and 5% CO2 for 4 hours. Subsequently, 10 µL of 500 ng / mL myostatin (Cat#120-00, Peprotech) was added to the cells, and the cells were incubated overnight. The next day, 100 µL of ONE-Step Luciferase Detection reagent (BPS Bioscience) was added to the cell solution (both solutions were equilibrated to room temperature), and after incubation on a plate shaker for 15 minutes, luminescence was measured using an Envision plate reader. Example 2.6: Activin Inhibition (SMAD RGA Test) To evaluate the efficacy and potency of the inhibition of ActRIIA and ActRIIB, candidate substances were characterized in an activin-stimulated SMAD RGA assay. TGFB / SMAD signaling pathway SBE reporter HEK293 cells (BPS BioScience) were washed with PBS, separated using 0.05% trypsin, and seeded into 96-well white flat-bottom plates at 35,000 cells / well with 100 µL of medium (MEM medium, 10% FBS, 1% NEAA, 1 mM sodium pyruvate, 1% Pen / Strep). The next day, the medium was replaced with 90 µL of assay medium (MEM medium, 0.5% FBS, 1% NEAA, 1 mM sodium pyruvate, 1% Pen / Strep) containing diluted antibodies of interest (10 to 0.00015 μg / mL) or controls. Cells were incubated at 37°C and 5% CO2 for 4 hours. Subsequently, 10 µL of 10 ng / mL Activin A (Cat#120-14E, Peprotech) was added to the cells, and the cells were incubated overnight. The next day, 100 µL of ONE-Step Luciferase Detection reagent (BPS Bioscience) was added to the cell solution (both solutions were equilibrated to room temperature), and after incubation on a plate shaker for 15 minutes, luminescence was measured using an Envision plate reader. Example 2.7: Measurement of non-specific binding To compare the non-specific binding behavior of various candidate substances, FACS EC50 values ​​were determined in HEK293 cells expressing ActRIIA and ActRIIB. Cells were treated with activin at a saturated concentration to block specific binding. To determine specific binding, the same experimental setup was performed without activin treatment. HEK293 cells (BPS BioScience) were washed with PBS, desorbed using TrypLE, and seeded at a rate of 100,000 cells per well in 100 µL of FACS buffer (PBS + 2% FBS + 1 mM EDTA) in 96-well round-bottom plates. Cells were washed once with FACS buffer and resuspended in 20 µL of 1.25 µg / mL activin solution (Cat#120-14E, Peprotech). After incubating cells on ice in a plate shaker for 30 minutes, 20 µL of antibody of interest (10 to 0.00064 µg / mL) or control was added. Cells were incubated on ice in a plate shaker for an additional 30 minutes. Subsequently, cells were washed twice with ice-cold FACS buffer, detection antibody diluted 1:200 (IgG(H+L) Cross-Adsorbed Goat anti-Human, Alexa Fluor® 488; #A11013, Thermo Fisher Scientific) was added, and cells were incubated on ice in the dark for 30 minutes. Cells were washed twice with FACS buffer, resuspended in 60 µL of FACS buffer, and the signal was analyzed on a Novocyte Quanteon flow cytometer. Example 2.8: Antibody generation The DNA encoding the antibody of the present disclosure was codon-optimized and cloned into an expression vector. After verifying the construct by sequencing, a plasmid was prepared. CHO K1 cells were transiently transfected with the plasmid, and antibodies were produced at a selected scale. The cell culture supernatant was collected and purified in two steps. The antibodies had a purity of over 95%, and the endotoxin levels were less than 0.5 EU / mg. The antibodies were resuspended at 1 to 5 mg / ml. Platform assays included A280, SDS-PAGE / Caliper-SDS (R&NR), SEC-HPLC, LC-MS, and endotoxin measurement. Example 3: CDR Optimization Approach Each CDR site within bimagrumab was independently diversified and analyzed on a yeast-based platform for mutations with improved affinity and reduced non-specific binding (PSR). After enrichment of candidates with beneficial properties, more than 70 bimagrumab derivatives with various mutations within the CDR were tested. The following characteristics were the main focus: ㆍ Increase in affinity for ActRIIA while maintaining affinity for ActRIIB, ㆍ Lower non-specific binding, and ㆍ Germline modification with lower immunogenicity risk. Finally, the following 15 conjugates were selected as the most promising antibodies: [Table 2] The antibody nomenclature used in the present invention refers to a specific combination of VH / VL pairs. Such antibodies may be used with different Fc variants (e.g., PA-LALA format or YTE mutation) or different invariant regions (e.g., human IgG1 invariant region or murine IgG2a invariant region) having any other mutation. The use of such formats or mutations is indicated in each example. Example 4: Characterization of the selected binder produced in Example 3 Example 4.1: Initial Bulk Characterization The panel of antibodies generated in Example 3 was compared to bimagrumab in terms of affinity for ActRIIA and their PSR scores. The PSR score is a measure of non-specific binding. The results are presented in Figure 2. Each data point represents a single antibody. Various antibodies can be generated, including antibodies with increased affinity for ActRIIA as well as antibodies with lower PSR scores (both compared to bimagrumab). This demonstrates that it is possible to generate improved variants of bimagrumab. Example 4.2: Reduced non-specific binding The selected antibodies were tested for non-specific binding on HEK cells. As described in more detail in Example 2.7, FACS binding EC50 values ​​were determined on HEK293 cells expressing ActRIIA and ActRIIB. Cells were treated with activin at a saturated concentration to block specific binding. The same experimental setup was performed without activin treatment to determine specific binding. The results are presented in Figure 3. As can be seen, non-specific binding was improved with the antibody Hepacnefpla and further improved with the antibody Hazaschlegel. Example 4.3: Heparin and HIC Score The selected antibodies were also tested for hydrophobic and charge-based interaction scores (calculated from the sum of HIC retention and heparin retention) as described in Example 1. The results are presented in Figure 4. It can be seen that certain derivatives of bimagrumab are improved in relation to their heparin scores and their PSR scores, and that these improvements are correlated with the PSR scores. Example 4.4: Affinity for ActRIIA and ActRIIB For the selected antibodies, the affinity for ActRIIA was measured. The results are shown in the table below (average data from at least two independent experiments). [Table 3] As can be seen, the tested antibody had at least 5 times higher affinity for ActRIIA compared to bimagrumab. This experiment was repeated for additional improved derivatives of bimagrumab. The results are shown in the table below (average data from at least two independent experiments). [Table 4A] A strong increase in affinity for ActRIIA was also observed compared to bimagrumab. Table 4B shows the affinity of the selected binders for ActRIIA and ActRIIB (average data from at least two independent experiments). [Table 4B] Example 4.5: Further Characterization Additional derivatives of bimagrumab were characterized for their affinity to ActRIIA, their affinity to ActRIIB, their activity in the Activin (SMAD RGA) assay, and their activity in the Myostatin (SMAD RGA) assay. The binders were tested as full-length immunoglobulins and as Fabs in all assays. The results are summarized in the table below. Results for the selected antibodies are also shown in Figures 9 (Activin assay) and 10 (Myostatin assay). Average data from at least two independent experiments are presented. [Table 5] Additionally, the selected binders were tested for their cross-reactivity with mouse ActRIIA, mouse ActRIIB, and cynomolgus monkey ActRIIB. The results are summarized in the table below (average data from at least two independent experiments). [Table 6A] The results for additional selected binders in the Activin SMAD RGA and Myostatin SMAD RGA tests are shown in Table 6B. [Table 6B] Example 4.6: Summary of the optimization process to date Significant progress has been made in the optimization process so far. Several antibodies, for example, antibody Ripla, showed a significant increase in efficacy compared to bimagrumab, while the pattern of non-specific binding remained constant. Another group of antibodies, for example, antibody Hazaschlegel, exhibited efficacy similar to bimagrumab but showed significant improvement in terms of non-specific binding. A third group of antibodies, for example, antibody Hepacnoffpla, exhibited intermediate characteristics, meaning that both efficacy and non-specific binding were improved compared to bimagrumab. In parallel with optimization on a yeast-based platform, computer simulation optimization was performed using Schroedinger modeling software. Affinity measurements for ActRIIB revealed that most binders did not exhibit higher affinity for ActRIIB, but rather much lower affinity. However, one of the binders, the antibody Baksutokes, demonstrated an affinity for ActRIIB that was at least as good as that of bimagrumab, and the other characteristics of the tested antibody Baksutokes made it a viable starting point for further optimization. The antibody Bakshutoikes has the following amino acid sequence: [Table 7] Example 5: Germ lineage conversion approach In the parallel approach, VH / VL pairs previously reported to generally possess improved biophysical properties were selected (reference [MAbs (2013) 5: 445-70]). Over 110 derivatives of bimagrumab with various mutations within the framework and CDR were tested. The objective was to identify variants with improved biophysical properties and reduced non-specific binding while maintaining bimagrumab-like affinity. Veradrec, an antibody and one of the binders, exhibited excellent biophysical properties and reduced non-specific binding while maintaining bimagrumab-like affinity. Due to these characteristics, this antibody became an ideal basis for combination with CDR-optimized candidates. The antibody Veradrec has the following amino acid sequence: [Table 8] In addition to the antibody Veradrec, which is optimized only at the framework site, the antibody Bevvalesgmyas was added to the framework and also included a CDR-optimized site to improve affinity for ActRIIA and B. The antibody Bevvalesgmyas has the following amino acid sequence: [Table 9] Example 6: Characterization of the selected binder produced in Example 5 Example 6.1: Melting temperature The measurement results of the melting temperatures for the selected binders are shown in Table 10. Many binders were superior to or similar to bimagrumab (average data from at least two independent experiments). [Table 10] The results of affinity measurements for ActRIIA and ActRIIB are shown in Figure 5. It can be seen that specific germline sequences led to increased affinity for both ActRIIA and ActRIIB. This was particularly pronounced in binders with the VH1-69 germline sequence. Additionally, these binders had shorter retention times in hydrophobic interchange chromatography (HIC). Example 6.2: Myostatin inhibition The results of myostatin inhibition measurements are shown in Table 11. Several binders had a superior IC50 than bimagrumab (average data from at least two independent studies). [Table 11] Example 7: Combination of improved characteristics Example 7.1: Creation of an additionally improved binder In the next optimization campaign, we tested whether the advantageous characteristics of the antibodies generated so far could be combined, and combined the optimized CDRs with framework candidates as shown in the table below. [Table 12] Example 7.2: Affinity for ActRIIA and ActRIIB In preliminary experiments, the affinity of the selected antibodies for ActRIIA was measured. The results are shown in the table below. [Table 13A] In a more detailed study, the affinity of the selected antibodies for ActRIIA was measured. The results are shown in the table below (average data from at least two independent experiments). [Table 13B] This experiment was repeated to evaluate whether the constant region of the antibody affects antibody affinity. The results are shown in Table 14 (average data from at least two independent experiments). [Table 14A] It was observed that the affinity of the antibody of the present disclosure is completely independent of the antibody format used. In a similar experiment, the affinity of the selected antibodies for ActRIIA and ActRIIB was measured. The results are shown in Table 14B (average data from at least two independent experiments). [Table 14B] Example 7.3: Reduced non-specific binding Selected antibodies were tested for non-specific binding on HEK cells (see Example 2.7). The results are presented in Figure 6. As can be seen, non-specific binding is improved for virtually all antibodies tested in this experiment. The least non-specific binding was observed in the antibodies Schvardamaga and Krappa. Example 7.4: Improved HIC score The selected antibodies were also tested for their HIC scores (see Example 2.2). Hydrophobicity increases with retention time. The results are presented in Figure 7. It can be seen that almost all tested antibodies had improved HIC scores compared to bimagrumab, including the antibodies Ofashluffer, Schvardamaga, and Zoidawurstle. Example 7.5: Reduced Charge-Based Interaction The selected antibodies were also tested for their charge-based interactions by heparin chromatography. The results are presented in Figure 8. Early elution times correlate with lower charge-based interactions. It can be seen that many of the tested antibodies had improved heparin scores compared to bimagrumab, including the antibodies Veradrek, Mauldasha, Metzelsuf, Nonnafürzla, Euerspetzla, Rauchfløisch, and Schwardamaga. Example 7.6: Improved myostatin inhibition (SMAD RGA assay) The results of myostatin inhibition measurements are shown in Table 15. Several binders had a superior IC50 compared to bimagrumab (average data from three independent trials). [Table 15] The results for additional selected binders in the myostatin SMAD RGA test are shown in Table 16B below. Example 7.7: Improved activin inhibition (SMAD RGA test) Preliminary experimental results of activin inhibition measurements are shown in the table below. Several binders had a superior IC50 compared to bimagrumab. [Table 16A] More detailed study results on activin inhibition measurements are shown in the table below. Several binders had superior IC90, IC95, and IC99 values ​​compared to bimagrumab (average data from 6 independent trials). [Table 16B] The results for additional selected binders in the Activin SMAD RGA and Myostatin SMAD RGA tests are shown in Table 16C. [Table 16C] Example 7.8: Reduced viscosity The binder was also rheologically characterized using an Anton Paar AMCR102 cone-plate rheometer (CP20-0.5). Shear rate ramping was performed at 20°C to define the shear rate exhibiting Newtonian behavior for subsequent viscosity measurements. Shear rate ramping was performed from 100 1 / s to 10000 1 / s, and a shear rate of 4000 1 / s, exhibiting Newtonian flow, was selected for sample analysis. Subsequently, viscosity was measured twice at 20°C and once at 5°C at a defined shear rate. The RSD between the two repeated measurements was less than 2% for all candidate molecules. The measured variants were formulated at a sample concentration of 180 mg / mL in 20 mM L-histidine, 160 mM sucrose, and 0.02% (v / v) PS80. The antibody bimagrumab (containing the LALA Fc modification) as well as the antibody ofashluffer (having a wild-type Fc region and an Fc region containing the PA-LALA modification) were tested. The results are presented in Table 17 and Figure 11. [Table 17] The measured viscosity of opaslupufer is lower than that of bimagrumab at both 5°C and 20°C, regardless of the Fc portion of the binder. The lower viscosity value of opaslupufer is attributed to the improved physicochemical properties of the molecule, such as reduced surface hydrophobicity. Example 8: In vivo efficacy study Male BALB SCID mice (Jackson labs, stock 001803) aged 7 to 8 weeks were randomized into treatment groups based on body weight prior to the start of the experiment. Mice were administered intravenously once a week for 4 weeks with a homologous control, bimagrumab (containing the LALA Fc variant), or the antibodies of opaschluffer, schvardamaga, or zoidawürstle (all containing the PA-LALA Fc variant). Body weight was monitored at least twice a week throughout the treatment course. After 4 weeks, mice were euthanized by CO2 inhalation, and necropsy and skeletal muscle tissues were collected. Exemplary results for the antibody ofaschluffer are shown in Figures 12 and 13 (essentially identical results were obtained with the antibodies Schvardamaga and Zoidaburstle). The results show that the administration of bimagrumab and ofaschluffer promoted body weight gain (Figure 12) and skeletal muscle hypertrophy in all examined muscles (Figure 13) in a dose-dependent manner, and that the increase in BW and muscle hypertrophy were most evident at 5 and 10 mg / kg (Figures 12B and 12C; Figure 13). These results also demonstrate that ofaschluffer exhibits a significantly higher effect on body weight gain and muscle hypertrophy than bimagrumab at 5 and 10 mg / kg. In fact, the body weight effect of 5 mg / kg of opashluffer is greater than that of 5 mg / kg of bimagrumab and similar to that of 10 mg / kg of bimagrumab (Fig. 12D), which suggests that opashluffer has a twice greater effect than bimagrumab (depending on dose / exposure). Example 9: Pharmacokinetics in Cynomorgus Monkeys and Minipigs Bimagrumab (PA-LALA format) and the antibody ofashluffer were evaluated for their pharmacokinetic (PK) profiles in cynomolgus monkeys. Following a single IV administration of 30 mg / kg, the PK profile of ofashluffer showed higher exposure over a longer duration than that of bimagrumab (Fig. 16A). Indeed, ofashluffer showed approximately three times higher exposure (AUC) than bimagrumab at the same dose.0-inf It shows ) and a linear CL that is three times lower (Table 18). Bimagrumab and ofashluffer were also evaluated in minipigs for their PK characteristics after IV and SC administration. After a single SC administration of 12 mg / kg, the serum concentration of ofashluffer was also significantly higher and more sustained than that of bimagrumab (Fig. 16B), and the total exposure (AUC) of ofashluffer 0-inf The value was more than twice as high. The subcutaneous bioavailability (F) in minipigs was calculated to be approximately 93% for ofashluffer and approximately 45% for bimagrumab. Interestingly, the F of bimagrumab observed in minipigs predicts the F reported in humans (average popPK 41%; literature [Clin Pharmacokinet (2023) 62(1):141-55)]) very well. This provides high confidence in the predictability of the bioavailability of ofashluffer subcutaneous bioavailability in humans. Overall, these results demonstrate that ofashluffer has a much more favorable PK and subcutaneous uptake profile than bimagrumab. [Table 18]

Claims

Claim 1 An antibody or antibody fragment that specifically binds to human ActRIIA and ActRIIB, wherein the antibody or antibody fragment has a higher affinity for human ActRIIA than the antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO.

8. Claim 2 In claim 1, the antibody or antibody fragment has one or more of the following additional characteristics compared to an antibody or antibody fragment comprising a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 7, and the LCDR3 region of SEQ ID NO. 8: a) less non-specific binding, b) an improved HIC score, c) an improved heparin score, d) a lower IC95 in a myostatin inhibition assay, e) a lower IC95 in an activin inhibition assay, or f) reduced viscosity. Claim 3 In claim 1 or 2, the antibody or antibody fragment comprises: a) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 14; b) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 17, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 18; c) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 20, and the LCDR3 region of SEQ ID NO. 14; d) the HCDR1 region of SEQ ID NO. 3, the sequence a variable light chain comprising the HCDR2 region of number 11, the HCDR3 region of sequence number 5, the LCDR1 region of sequence number 22, the LCDR2 region of sequence number 13, and the LCDR3 region of sequence number 14; e) a variable light chain comprising the HCDR1 region of sequence number 3, the HCDR2 region of sequence number 4, the HCDR3 region of sequence number 5, the LCDR1 region of sequence number 6, the LCDR2 region of sequence number 13, and the LCDR3 region of sequence number 18; f) a variable light chain comprising the HCDR1 region of sequence number 3, the HCDR2 region of sequence number 11, the HCDR3 region of sequence number 5, the LCDR1 region of sequence number 26, the LCDR2 region of sequence number 13, and the LCDR3 region of sequence number 27; g) the HCDR1 region of sequence number 3, the HCDR2 region of sequence number 11, the HCDR3 region of sequence number 5, and the LCDR3 region of sequence number 29 Variable light chain comprising an LCDR1 region, an LCDR2 region of SEQ NO. 30 and an LCDR3 region of SEQ NO. 14, h) an HCDR1 region of SEQ NO. 3,An antibody or antibody fragment comprising: i) a variable light chain comprising the HCDR2 region of SEQ ID NO. 4, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 33, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 34; j) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 6, the LCDR2 region of SEQ ID NO. 13, and the LCDR3 region of SEQ ID NO. 14; and j) a variable light chain comprising the HCDR1 region of SEQ ID NO. 3, the HCDR2 region of SEQ ID NO. 11, the HCDR3 region of SEQ ID NO. 5, the LCDR1 region of SEQ ID NO. 22, the LCDR2 region of SEQ ID NO. 41, and the LCDR3 region of SEQ ID NO.

14. Claim 4 In any one of claims 1 to 3, the antibody or antibody fragment comprises: a) the variable heavy chain of SEQ ID NO. 12 and the variable light chain of SEQ ID NO. 15; b) the variable heavy chain of SEQ ID NO. 16 and the variable light chain of SEQ ID NO. 19; c) the variable heavy chain of SEQ ID NO. 16 and the variable light chain of SEQ ID NO. 21; d) the variable heavy chain of SEQ ID NO. 16 and the variable light chain of SEQ ID NO. 23; e) the variable heavy chain of SEQ ID NO. 24 and the variable light chain of SEQ ID NO. 25; f) the variable heavy chain of SEQ ID NO. 16 and the variable light chain of SEQ ID NO. 28; g) the variable heavy chain of SEQ ID NO. 16 and the variable light chain of SEQ ID NO. 31; h) the variable heavy chain of SEQ ID NO. 32 and the variable light chain of SEQ ID NO. 35; i) the variable heavy chain of SEQ ID NO. 36 and the variable light chain of SEQ ID NO. 15; j) the variable heavy chain of SEQ ID NO. 37 and the variable light chain of SEQ ID NO. 21; k) SEQ ID NO. An antibody or antibody fragment comprising: l) the variable heavy chain of 37 and the variable light chain of SEQ ID NO. 23; m) the variable heavy chain of SEQ ID NO. 38 and the variable light chain of SEQ ID NO. 23; n) the variable heavy chain of SEQ ID NO. 37 and the variable light chain of SEQ ID NO. 39; or o) the variable heavy chain of SEQ ID NO. 37 and the variable light chain of SEQ ID NO.

42. Claim 5 An antibody according to any one of claims 1 to 4, wherein the antibody comprises a modification in the Fc region that increases the half-life of the antibody, and preferably, said modification is a YTE mutation (M252Y / S254T / T256E). Claim 6 An antibody according to any one of claims 1 to 5, wherein the antibody comprises a silencing modification in the Fc region, preferably the silencing modification is a PA-LALA, PG-LALA, or AEASS mutation. Claim 7 In any one of claims 1 to 6, the antibody or antibody fragment is an antibody or antibody fragment that is conjugated or fused to a pharmaceutically active moiety. Claim 8 An antibody or antibody fragment according to any one of claims 1 to 7 for use in medicine, wherein the use in medicine is preferably for the treatment of metabolic diseases, obesity, type 2 diabetes or cardiovascular diseases. Claim 9 A nucleic acid composition comprising a nucleic acid sequence encoding an antibody or antibody fragment according to any one of claims 1 to 7, or a plurality of nucleic acid sequences. Claim 10 A vector comprising the nucleic acid composition of claim 9. Claim 11 A host cell comprising the vector of claim 10 or the nucleic acid composition of claim 9. Claim 12 A pharmaceutical composition comprising an antibody or antibody fragment according to any one of claims 1 to 7 and a pharmaceutically acceptable carrier or excipient. Claim 13 An antibody or antigen-binding fragment thereof that binds to ActRIIB, comprising: a) a heavy chain variable region CDR1 having the amino acid sequence of SEQ ID NO. 3; b) a heavy chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 11; c) a heavy chain variable region CDR3 having the amino acid sequence of SEQ ID NO. 5; d) a light chain variable region CDR1 having the amino acid sequence of SEQ ID NO. 22; e) a light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 13; and f) a light chain variable region CDR3 having the amino acid sequence of SEQ ID NO.

14. Claim 14 In claim 13, an antibody or an antigen-binding fragment thereof comprising: a) a heavy chain variable region CDR1 having the amino acid sequence of SEQ ID NO. 3; b) a heavy chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 11; c) a heavy chain variable region CDR3 having the amino acid sequence of SEQ ID NO. 5; d) a light chain variable region CDR1 having the amino acid sequence of SEQ ID NO. 22; e) a light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 13; and f) a light chain variable region CDR3 having the amino acid sequence of SEQ ID NO.

14. Claim 15 A monoclonal antibody or its antigen-binding fragment comprising a heavy chain variable region having the amino acid sequence of SEQ ID NO. 16 and a light chain variable region having the amino acid sequence of SEQ ID NO.

23. Claim 16 An antibody or antigen-binding fragment thereof that binds to ActRIIB, comprising: a) a heavy chain variable region CDR1 having the amino acid sequence of SEQ ID NO. 3; b) a heavy chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 11; c) a heavy chain variable region CDR3 having the amino acid sequence of SEQ ID NO. 5; d) a light chain variable region CDR1 having the amino acid sequence of SEQ ID NO. 29; e) a light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 30; and f) a light chain variable region CDR3 having the amino acid sequence of SEQ ID NO.

14. Claim 17 In claim 16, an antibody or an antigen-binding fragment thereof comprising: a) a heavy chain variable region CDR1 having the amino acid sequence of SEQ ID NO. 3; b) a heavy chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 11; c) a heavy chain variable region CDR3 having the amino acid sequence of SEQ ID NO. 5; d) a light chain variable region CDR1 having the amino acid sequence of SEQ ID NO. 29; e) a light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 30; and f) a light chain variable region CDR3 having the amino acid sequence of SEQ ID NO.

14. Claim 18 A monoclonal antibody or its antigen-binding fragment comprising a heavy chain variable region having the amino acid sequence of SEQ ID NO. 16 and a light chain variable region having the amino acid sequence of SEQ ID NO.

31. Claim 19 An antibody or antigen-binding fragment thereof that binds to ActRIIB, comprising: a) a heavy chain variable region CDR1 having the amino acid sequence of SEQ ID NO. 3; b) a heavy chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 4; c) a heavy chain variable region CDR3 having the amino acid sequence of SEQ ID NO. 5; d) a light chain variable region CDR1 having the amino acid sequence of SEQ ID NO. 33; e) a light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 13; and f) a light chain variable region CDR3 having the amino acid sequence of SEQ ID NO.

34. Claim 20 In claim 19, an antibody or an antigen-binding fragment thereof comprising: a) a heavy chain variable region CDR1 having the amino acid sequence of SEQ ID NO. 3; b) a heavy chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 4; c) a heavy chain variable region CDR3 having the amino acid sequence of SEQ ID NO. 5; d) a light chain variable region CDR1 having the amino acid sequence of SEQ ID NO. 33; e) a light chain variable region CDR2 having the amino acid sequence of SEQ ID NO. 13; and f) a light chain variable region CDR3 having the amino acid sequence of SEQ ID NO.

34. Claim 21 A monoclonal antibody or its antigen-binding fragment comprising a heavy chain variable region having the amino acid sequence of SEQ ID NO. 32 and a light chain variable region having the amino acid sequence of SEQ ID NO.

35. Claim 22 A monoclonal antibody or antigen-binding fragment according to any one of claims 13 to 21, wherein the Fc region of the antibody or antigen-binding fragment comprises a mutation that increases the half-life. Claim 23 In paragraph 22, the mutation that increases the half-life is a monoclonal antibody or antigen-binding fragment that is a YTE (M252Y / S254T / T256E) mutation. Claim 24 A monoclonal antibody or antigen-binding fragment according to any one of claims 13 to 21, wherein the antibody or antigen-binding fragment comprises a silencing modification within the Fc region, wherein the silencing modification is a PA-LALA, PG-LALA, or AEASS mutant. Claim 25 A pharmaceutical composition comprising a monoclonal antibody or antigen-binding fragment of any one of claims 13 to 24 and a pharmaceutically acceptable carrier or excipient. Claim 26 A method for treating an ActRIIA or ActRIIB-mediated disease or condition in a subject requiring treatment, comprising the step of administering to the subject an antibody or antibody fragment according to any one of claims 13 to 24 or a pharmaceutical composition of claim 25. Claim 27 In paragraph 26, the ActRIIA or ActRIIB-mediated disease or disorder is a metabolic disease. Claim 28 In paragraph 26, the ActRIIA or ActRIIB-mediated disease or condition is obesity or type 2 diabetes. Claim 29 In paragraph 26, the ActRIIA or ActRIIB-mediated disease or disorder is a cardiovascular disease.

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