Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use

Abstract

This disclosure provides anti-myosin antibodies and methods for their formation and use. It also provides nucleic acids encoding anti-myosin antibodies and host cells comprising the aforementioned nucleic acids. This disclosure further provides polypeptides containing a variant Fc region and methods for their formation and use. It also provides nucleic acids encoding the polypeptides and host cells comprising the aforementioned nucleic acids.

Description

Anti-Myostatin Antibodies, Polypeptides Comprising Variant Fc Regions, and Methods of Use This invention relates to anti-myostatin antibodies and methods of using the same. This invention also relates to polypeptides comprising variant Fc regions and methods of using the same. Myostatin, also known as growth differentiation factor 8 (GDF8), is a secreted protein and a member of the transforming growth factor-β (TGF-β) superfamily of proteins. Members of this superfamily have properties of growth regulation and morphogenesis (see, for example, Non-Patent Document 1, Non-Patent Document 2, and Patent Document 1). Myostatin is predominantly expressed in developing and adult skeletal muscle and acts as a negative regulator of muscle growth. Systemic overexpression of myostatin in adult mice results in muscle atrophy (see, for example, Non-Patent Document 3), whereas, conversely, myostatin knockout mice are characterized by hypertrophy and hyperplasia of skeletal muscle, resulting in muscle mass that is two to three times greater than that of their wild-type littermates (see, for example, Non-Patent Document 4). Like other members of the TGF-β family, myostatin is synthesized as a large precursor protein that contains an N-terminal propeptide domain and a C-terminal domain that is considered the active molecule (see, for example, Non-Patent Document 5 and Patent Document 2). Two molecules of the myostatin precursor are covalently linked by a single disulfide bond present in the C-terminal growth factor domain. The active mature myostatin (a disulfide-bonded homodimer composed of the C-terminal growth factor domain) is released from the myostatin precursor through multiple steps of proteolytic processing. In the first step of the myostatin activation pathway, the peptide bond, Arg266-Asp267, between the N-terminal propeptide domain and the C-terminal growth factor domain is cleaved in both chains of the homodimer precursor by a furin-type proprotein convertase. However, the three resulting peptides (two propeptides and one mature myostatin) (i.e., the disulfide-bonded homodimer composed of the growth factor domain)) still remain associated, forming a non-covalently bound inactive complex that is referred to as "latent myostatin". Mature myostatin can then be released from latent myostatin through degradation of the propeptide. A member of the bone morphogenetic protein 1 (BMP1) family of metalloproteinases cleaves a single peptide bond, Arg98-Asp99, within the propeptide, accompanied by the release of mature, active myostatin, a homodimer (see, for example, Non-Patent Document 6). In addition, latent myostatin can be activated in vitro ( in vitro) by dissociating the complex with acid or heat treatment (see, for example, Non-Patent Document 7). Myostatin exerts its effects through a family of transmembrane serine / threonine kinase heterotetrameric receptors, the activation of which enhances receptor transphosphorylation, resulting in the stimulation of serine / threonine kinase activity. It has been shown that the myostatin pathway involves the binding of active myostatin dimers to the high-affinity activin receptor type IIB (ActRIIB), which then recruits and activates the transphosphorylation of the low-affinity receptor-like activin kinase 4 (ALK4) / activin receptor-like kinase 5 (ALK5). It has also been shown that the proteins Smad 2 and Smad 3 are then activated and form a complex with Smad 4, which then translocates to the nucleus for the activation of target gene transcription. ActRIIB has been demonstrated to be able to mediate the effects of myostatin in vivo ( in vivo), since the expression of a dominant negative form of ActRIIB in mice mimics myostatin gene knockout (see, for example, Non-Patent Document 8). Many diseases and conditions are associated with muscle atrophy (e.g., reduction or impaired function of muscle tissue), such as muscular dystrophy (MD; including Duchenne muscular dystrophy), amyotrophic lateral sclerosis (ALS), sarcopenia, organ atrophy, cachexia, chronic obstructive pulmonary disease (COPD), muscle wasting, and cachexia caused by cancer or other diseases, as well as kidney diseases, heart failure or diseases, and liver diseases. An increase in muscle mass and / or muscle strength would be beneficial to patients; however, current treatments available for these diseases are limited. Therefore, due to its role as a negative regulator of skeletal muscle growth, myostatin is an ideal target for therapeutic or preventive intervention in such diseases or conditions, or for monitoring the progression of such diseases or conditions. In particular, agents that inhibit the activity of myostatin may be therapeutically beneficial. Inhibition of myostatin expression results in muscle hypertrophy and hyperplasia (Non-Patent Document 4). Myostatin negatively regulates muscle regeneration after injury, and the lack of myostatin in myostatin-null mice results in accelerated muscle regeneration (see, for example, Non-Patent Document 9). Anti-myostatin (GDF8) antibodies have been described, for example, in Patent Document 3, Patent Document 4, Patent Document 5, Patent Document 6, and Patent Document 7, and Patent Document 8, Patent Document 9, and Patent Document 10 have shown to bind to myostatin and inhibit myostatin activity in vitro and in vivo, including myostatin activity related to the negative regulation of skeletal muscle mass. In the skeletal muscle of wild-type mice (see, for example, Non-Patent Document 10) and in mdx mice, a model of muscular dystrophy (see, for example, Non-Patent Document 11, Non-Patent Document 12), myostatin-neutralizing antibodies increase body weight, skeletal muscle mass, and muscle size and strength. However, these prior art antibodies are specific for mature myostatin rather than latent myostatin, and the strategies for inhibiting myostatin activity utilize antibodies that can bind to and neutralize mature myostatin. Antibodies are attracting attention as drugs because they are highly stable in the blood and have few side effects (see, for example, Non-Patent Document 13 and Non-Patent Document 14). Almost all therapeutic antibodies on the current market are antibodies of the human IgG1 subclass. One of the known functions of IgG subclass antibodies is antibody-dependent cell-mediated cytotoxicity (hereinafter referred to as ADCC activity) (see, for example, Non-Patent Document 15). For an antibody that exhibits ADCC activity, the Fc region of the antibody must bind to the Fcγ receptor (hereinafter referred to as FcγR), which is an antibody-binding receptor present on the surface of effector cells such as killer cells, natural killer cells, and activated macrophages. In humans, FcγRIa (CD64A), FcγRIIa (CD32A), FcγRIIb (CD32B), FcγRIIIa (CD16A), and FcγRIIIb (CD16B) isoforms have been reported as members of the FcγR protein family, and their respective allotypes have also been reported (see, for example, Non-Patent Document 16). FcγRIa, FcγRIIa, and FcγRIIIa are called activating FcγRs because they have immunologically active functions, while FcγRIIb is called an inhibitory FcγR because it has immunosuppressive functions (see, for example, Non-Patent Document 17). In the binding between the Fc region and FcγR, many amino acid residues in the antibody hinge region and CH2 domain, and the sugar chain attached to Asn binding to the CH2 domain at position 297 (EU numbering) have been shown to be important (see, for example, Non-Patent Document 18, Non-Patent Document 19, and Non-Patent Document 20). To date, many variants with FcγR binding properties, mainly antibodies with mutations introduced at these positions, have been studied; and Fc region variants with higher binding activity to activated FcγR have been obtained (see, for example, Patent Document 11, Patent Document 12, Patent Document 13, and Patent Document 14). When activated FcγR crosslinks with immune complexes, it phosphorylates immunoreceptor tyrosine-based activating motifs (ITAM) contained in the intracellular domain or the common γ chain (interaction partner) of FcR, activates the signal transducer SYK, and initiates an inflammatory immune response by activating the activation signal cascade (see, for example, Non-Patent Document 21). FcγRIIb is the only FcγR expressed on B cells (see, for example, Non-Patent Document 22). The interaction between the antibody Fc region and FcγRIIb has been reported to inhibit the primary immune response of B cells (see, for example, Non-Patent Document 23). In addition, it has been reported that when FcγRIIb and the B cell receptor (BCR) on B cells are crosslinked by immune complexes in the blood, the activation of B cells and the antibody production of B cells are inhibited (see, for example, Non-Patent Document 24). In this immune inhibitory signal transduction mediated by BCR and FcγRIIb, the immunoreceptor tyrosine inhibitory motif (ITIM) contained in the intracellular domain of FcγRIIb is necessary (see, for example, Non-Patent Document 25 and Non-Patent Document 26). When ITIM is phosphorylated by a signal, SH2-containing inositol polyphosphate 5-phosphatase (SHIP) is recruited, the transmission of other activated FcγR signal cascades is inhibited, and the inflammatory immune response is inhibited (see, for example, Non-Patent Document 27). In addition, the aggregation of FcγRIIb alone has been reported to transiently inhibit calcium ion influx, resulting in BCR crosslinking and B cell proliferation in a BCR-independent manner without inducing apoptosis of B cells that do not produce IgM (see, for example, Non-Patent Document 28). FcγRIIb is also expressed on dendritic cells, macrophages, activated neutrophils, mast cells, and basophils. FcγRIIb inhibits the functions of activated FcγR, such as phagocytosis and the release of inflammatory cytokines in these cells, and inhibits the inflammatory immune response (see, for example, Non-Patent Document 17). To date, the importance of the immunosuppressive function of FcγRIIb has been elucidated by studies using FcγRIIb knockout mice. It has been reported that in FcγRIIb knockout mice, humoral immunity is not properly regulated (see, for example, Non-Patent Document 29), the sensitivity to collagen-induced arthritis (CIA) increases (see, for example, Non-Patent Document 30), lupus-like symptoms appear, and Goodpasture's syndrome-like symptoms appear (see, for example, Non-Patent Document 31). In addition, insufficient control of FcγRIIb has been reported to be associated with human autoimmunity. For example, the relationship between gene polymorphisms in the transmembrane region and the promoter region of FcγRIIb and the incidence of systemic lupus erythematosus (SLE) (see, for example, Non-Patent Documents 32, 33, 34, 35, and 36), and the reduced expression of FcγRIIb on B cells in SLE patients (see, for example, Non-Patent Documents 37 and 38) have been reported. From the above mouse models and clinical findings, FcγRIIb is considered to play a role in controlling autoimmune and inflammatory diseases through a specific association with B cells, and it is a potential target molecule for controlling autoimmune and inflammatory diseases. IgG1, which is mainly a commercially available therapeutic antibody, is known to not only bind to FcγRIIb but also strongly activate FcγR (see, for example, Non-Patent Document 39). By using an Fc region with enhanced FcγRIIb binding or improved FcγRIIb binding selectivity compared to activated FcγR, it is possible to develop therapeutic antibodies with stronger immunosuppressive properties than IgG1. For example, it has been proposed that using antibodies with variant regions that bind to the BCR and Fc with enhanced FcγRIIb binding force can inhibit B cell activation (see, for example, Non-Patent Document 40). It has been reported that crosslinking FcγRIIb to B cells and IgE that bind to the B cell receptor inhibits the differentiation of B cells into plasma cells, resulting in the inhibition of IgE production; and in mice transplanted with human PBMC, the concentrations of human IgG and IgM are maintained while the concentration of human IgE decreases (see, for example, Non-Patent Document 41). In addition to IgE, it has been reported that when FcγRIIB and CD79b, which is a component molecule of the B cell receptor complex, are crosslinked by an antibody, B cell proliferation in vitro is inhibited, and joint inflammatory symptoms in a collagen-induced arthritis model are alleviated (see, for example, Non-Patent Document 42). In addition to B cells, it has been reported that cross-linking of FcεRI and FcγRIIb on mast cells using a molecule in which the Fc portion of IgG with enhanced FcγRIIb binding affinity is fused to the Fc portion of IgE, which binds to the IgE receptor FcεRI, results in phosphorylation of FcγRIIb, thereby inhibiting FcεRI-dependent calcium influx. This indicates that inhibition of degranulation through FcγRIIb stimulation is possible by enhancing FcγRIIb binding affinity (see, for example, Non-Patent Document 43). Therefore, antibodies with Fc having improved FcγRIIb binding activity are shown to have potential as therapeutic agents for inflammatory diseases such as autoimmune diseases. In addition, it has been reported that activation of macrophages and dendritic cells through Toll-like receptor 4 due to LPS stimulation is inhibited in the presence of antibody-antigen immune complexes, and this effect is also shown to be the action of immune complexes through FcγRIIb (see, for example, Non-Patent Document 44 and Non-Patent Document 45). Therefore, the use of antibodies with enhanced FcγRIIb binding affinity is expected to increase the inhibitory effect on TLR-mediated activation signals; thus, such antibodies have been shown to have potential as therapeutic agents for inflammatory diseases such as autoimmune diseases. In addition, mutants with enhanced FcγRIIb binding affinity have been shown to have potential as therapeutic agents for cancer and for inflammatory diseases such as autoimmune diseases. To date, it has been found that FcγRIIb plays an important role in the agonistic activity of agonist antibodies against the TNF receptor superfamily. In particular, interaction with FcγRIIb has been shown to be required for the agonistic activity of antibodies against CD40, DR4, DR5, CD30, and CD137 included in the TNF receptor family (see, for example, Non-Patent Document 46, Non-Patent Document 47, Non-Patent Document 48, Non-Patent Document 49, Non-Patent Document 50, Non-Patent Document 51, and Non-Patent Document 52). Non-Patent Document 46 shows that the use of an antibody with enhanced FcγRIIb binding affinity increases the antitumor effect of an anti-CD40 antibody. Therefore, antibodies with enhanced FcγRIIb binding affinity are expected to have the effect of increasing the agonistic activity of agonist antibodies, including antibodies against the TNF receptor superfamily. In addition, it has been shown that when an antibody of the recognition Kit is used to crosslink FcγRIIb and Kit on cells expressing Kit, which is a type of receptor tyrosine kinase (RTK), cell proliferation is inhibited. Similar effects have been reported even in cases where such Kit is continuously activated and has mutations that lead to tumor formation (see, for example, Non-Patent Document 53). Therefore, the use of an antibody having enhanced FcγRIIb binding ability is expected to increase the inhibitory effect on cells expressing RTK with continuously activated mutations. Antibodies of Fc with improved FcγRIIb binding activity have been reported (see, for example, Non-Patent Document 40). In this document, the FcγRIIb binding activity was improved by adding alterations such as S267E / L328F, G236D / S267E, and S239D / S267E to the Fc region of the antibody. Among them, the antibody into which the S267E / L328F mutation was introduced binds most strongly to FcγRIIb and maintains the same level of binding to FcγRIa and FcγRIIa of the H type, in which the residue at position 131 of FcγRIIa is His, the same as that of naturally occurring IgG1. However, another report shows that this modification increases the binding to FcγRIIa of the R type hundreds of times to the same level as the binding to FcγRIIb, in which the residue at position 131 of FcγRIIa of the R type is Arg, which means that the binding selectivity for FcγRIIb has not been improved compared to FcγRIIa of the R type (see, for example, Patent Document 15). Only the effect of enhancing FcγRIIa binding, rather than an increase in FcγRIIb binding, is considered to have an impact on cells expressing FcγRIIa but not FcγRIIb, such as platelets (see, for example, Non-Patent Document 17). For example, it is known that patients administered bevacizumab, an antibody against VEGF, have a higher risk of having thromboembolism (see, for example, Non-Patent Document 54). In addition, similar thromboembolism has been observed in clinical development tests of antibodies against CD40 ligand, and the clinical tests were interrupted (see, for example, Non-Patent Document 55). In the case of these antibodies, subsequent studies using animal models, etc. have shown that the administered antibodies aggregate platelets by binding to FcγRIIa on platelets and form thrombi (see, for example, Non-Patent Document 56 and Non-Patent Document 57). In systemic lupus erythematosus, an autoimmune disease, platelets are activated through an FcγRIIa-dependent mechanism, and it has been reported that platelet activation is related to the severity of symptoms (see, for example, Non-Patent Document 58). Administering an antibody with enhanced FcγRIIa binding to such patients who already have a higher risk of thromboembolism disease onset will increase the risk of thromboembolism disease onset, and thus is quite dangerous. In addition, antibodies with enhanced FcγRIIa binding have been reported to enhance macrophage-mediated antibody-dependent cell phagocytosis (ADCP) (see, for example, Non-Patent Document 59). When an antigen bound by an antibody is phagocytosed by a macrophage, the antibody itself is considered to be phagocytosed simultaneously. When an antibody is administered as a drug, peptide fragments from the administered antibody are likely to be presented as antigens as well, thus increasing the risk of generating antibodies against the therapeutic antibody (anti-therapeutic antibody). More specifically, enhancing the binding of FcγRIIa will increase the risk of generating antibodies against the therapeutic antibody, and this will significantly reduce their value as drugs. In addition, FcγRIIb on dendritic cells has been shown to contribute to peripheral tolerance by inhibiting dendritic cell activation generated by immune complexes formed between antigens and antibodies, or by inhibiting antigen-presenting cells from presenting antigens to T cells by activating Fcγ receptors (see, for example, Non-Patent Document 60). Since FcγRIIa is also expressed on dendritic cells, when an Fc with enhanced selective binding to FcγRIIb is used as a drug, due to the enhanced selective binding to FcγRIIb, antigens are not easily presented by dendritic cells, and the risk of generating anti-drug antibodies can be relatively reduced. In this regard, such antibodies can also be useful. More specifically, when the binding of FcγRIIa is enhanced, it leads to an increased risk of thrombus formation through platelet aggregation and an increased risk of generating anti-therapeutic antibodies due to increased immunogenicity, and its value as a drug will be significantly reduced. From such a perspective, compared to naturally occurring IgG1, the above-described Fc variant with enhanced FcγRIIb binding shows significantly enhanced binding to R-type FcγRIIa. Therefore, its value as a drug for patients with R-type FcγRIIa is significantly reduced. H-type and R-type FcγRIIa are observed at roughly the same frequency in Caucasians and African Americans (see, for example, Non-Patent Document 61 and Non-Patent Document 62). Therefore, when this Fc variant is used for the treatment of autoimmune diseases, the number of patients who can be safely treated and enjoy its effect as a drug will be limited. In addition, it has been reported that in dendritic cells lacking FcγRIIb, or in dendritic cells in which the interaction between FcγRIIb and the Fc portion of the antibody is inhibited by an anti-FcγRIIb antibody, the dendritic cells are mature (see, for example, Non-Patent Document 63 and Non-Patent Document 64). This report shows that in a stable state without inflammation and activation, FcγRIIb actively inhibits the maturation of dendritic cells. In addition to FcγRIIb, FcγRIIa is also expressed on the surface of dendritic cells; therefore, even if the binding to inhibitory FcγRIIb is enhanced and even if the binding to activating FcγRs (such as FcγRIIa) is enhanced, the maturation of dendritic cells can be promoted. More specifically, not only improving the FcγRIIb binding activity, but also improving the ratio of FcγRIIb binding activity to FcγRIIa binding activity is considered important in providing antibody immunosuppressive effects. Therefore, when considering the production of drugs that utilize the immunosuppressive effect mediated by FcγRIIb binding, the Fc variant not only needs to have enhanced FcγRIIb binding activity but also needs to have heterotypic binding to H- and R-type FcγRIIa, which is maintained at the same level or weakened to a lower level compared to naturally occurring IgG1. At the same time, there have been reports of examples of introducing amino acid changes in the Fc region to increase FcγRIIb binding selectivity (see, for example, Non-Patent Document 65). However, in the reports of this document, it is claimed that all variants with improved FcγRIIb selectivity show reduced FcγRIIb binding compared to naturally occurring IgGl. Therefore, these variants are considered to be practically difficult to induce FcγRIIb-mediated immunosuppressive effects more strongly than IgGl. In addition, since FcγRIIb plays an important role in the aforementioned activating antibodies, enhancing their binding activity is expected to enhance the activating activity. However, when the binding of FcγRIIa is also enhanced, unplanned effects (such as ADCC activity and ADCP activity) will appear, and this may cause side effects. From the above perspective, it is preferable to selectively enhance the binding activity of FcγRIIb. From these results, it can be seen that when manufacturing therapeutic antibodies for treating autoimmune diseases and cancers using FcγRIIb, compared with naturally occurring IgG, maintaining or reducing the binding activity to FcγRIIa isoforms and enhancing the binding to FcγRIIb is important. However, in the extracellular region, FcγRIIb has 93% sequence identity with FcγRIIa, one of the activated FcγRs, and they are very similar in structure. FcγRIIa has isoforms, H-type and R-type, with the amino acid at position 131 being His (H-type) or Arg (R-type), but their interactions with antibodies are different (see, for example, Non-Patent Document 66). Therefore, manufacturing Fc region variants with enhanced selective FcγRIIb binding compared to each isoform of FcγRIIa may be a difficult task, which involves distinguishing the highly homologous sequences between FcγRIIa and FcγRIIb. Despite these difficulties, through comprehensive amino acid modification analysis in the Fc region, many Fc region variants with selective binding activity to FcγRIIb compared to FcγRIIa have been identified to date (see, for example, Patent Document 16, Patent Document 17, Patent Document 18, Patent Document 19, and Patent Document 20). Currently, there have been reports on Fc region variants with binding selectivity for FcγRIIb related to human FcγR, but there are no reports on Fc region variants with binding selectivity for FcγRIIb related to monkey FcγR. Due to the lack of such Fc variants, the effect of selectively binding of Fc variants to FcγRIIb has not been thoroughly studied in monkeys. In addition to the above, it has been reported that by modifying the charge of amino acid residues that may be exposed on the surface of the antibody, it is possible to increase or decrease the isoelectric point (pI) of the antibody, making it possible to adjust the half-life of the antibody in the blood (see, for example, Patent Document 21 and Patent Document 22). It shows that it is possible to extend the plasma half-life of the antibody by reducing the pI of the antibody, and vice versa. In addition, it has been reported that the charge of specific amino acid residues can be modified, particularly in its CH3 domain, to increase the pI of an antibody, thereby promoting antigen incorporation into cells (see, for example, Patent Document 23). It has also been reported that modifying the charge of amino acid residues in the antibody constant region (mainly the CH1 domain) to lower the pI can extend the half-life of the antibody in plasma (see, for example, Patent Document 24). 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Invest. 97:1348-1354 (1996) [Non-Patent Document 62] Manger et al., Arthritis Rheum. 41:1181-1189 (1998) [Non-Patent Document 63] Boruchov et al., J. Clin. Invest. 115:2914-2923 (2005) [Non-Patent Document 64] Dhodapkar et al., Proc. Natl. Acad. Sci. USA 102:2910-2915 (2005) [Non-Patent Document 65] Armour et al., Mol. Immunol. 40:585-593 (2003) [Non-Patent Document 66] Warmerdam et al., J. Exp. Med. 172:19-25 (1990) An object of the present invention is to provide an antibody against myostatin, a polypeptide containing a variant Fc region, and methods for using the same. The present invention provides an antibody against myostatin and methods for using the same. The present invention also provides a protein containing a variant Fc region and methods for using the same. In some embodiments, the isolated myostatin antibody of the present invention binds to latent myostatin. In still other embodiments, the antibody binds to an epitope in a fragment consisting of amino acids 21-100 of the propeptide of myostatin (SEQ ID NO: 78). In some embodiments, the isolated myostatin antibody of the present invention inhibits the activation of myostatin. In still other embodiments, the antibody blocks the release of mature myostatin from latent myostatin. In still other embodiments, the antibody blocks the proteolytic release of mature myostatin. In still other embodiments, the antibody blocks the spontaneous release of mature myostatin. In still other embodiments, the antibody does not bind to mature myostatin. In still other embodiments, the antibody binds to the same epitope as the antibody described in Table 13. In still other embodiments, the antibody binds to the same epitope as the antibody comprising the VH and VL pair described in Table 13. In still other embodiments, the antibody binds to the same epitope as the antibody described in Table 2a. In still other embodiments, the antibody binds to the same epitope as the antibody comprising the VH and VL pair described in Table 2a. In still other embodiments, the antibody binds to the same epitope as the antibody described in Table 11a. In still other embodiments, the antibody binds to the same epitope as the antibody comprising the VH and VL pair described in Table 11a. In still other embodiments, the antibody binds to the same epitope as the antibody described in Table 2a, 11a or 13. In still other embodiments, the antibody binds to the same epitope as the antibody comprising the VH and VL pair described in Table 2a, 11a or 13. In some embodiments, the isolated myostatin antibody of the present invention binds to latent myostatin with higher affinity at neutral pH than at acidic pH. In some embodiments, the myostatin antibody binds to latent myostatin with higher affinity at pH 7.4 than at pH 5.8. In some embodiments, the isolated myostatin antibody of the present invention binds to a polypeptide fragment consisting of amino acids 21-100 of myostatin propeptide (SEQ ID NO: 78) with higher affinity at pH 7.4 than at pH 5.8. In some embodiments, the antibody binds to a myostatin epitope with higher affinity at neutral pH than at acidic pH, which is the same as the myostatin epitope bound by the antibody described in Table 13. In some additional embodiments, the myostatin antibody binds to an epitope with higher affinity at pH 7.4 than at pH 5.8, which is the same as the epitope bound by the antibody described in Table 13. In still other embodiments, the antibody binds to an epitope with higher affinity at pH 7.4 than at pH 5.8, which is the same as the epitope bound by the antibody comprising the VH and VL pair described in Table 13. In some embodiments, the antibody binds to a myostatin epitope with higher affinity at neutral pH than at acidic pH, which is the same as the myostatin epitope bound by the antibody described in Table 2a. In some embodiments, the antibody binds to a myostatin epitope with higher affinity at pH 7.4 than at pH 5.8, which is the same as the myostatin epitope bound by the antibody described in Table 2a. In still other embodiments, the antibody binds to an epitope with higher affinity at pH 7.4 than at pH 5.8, which is the same as the epitope bound by the antibody comprising the VH and VL pair described in Table 2a. In some additional embodiments, the myostatin antibody binds to an epitope with higher affinity at neutral pH than at acidic pH, which is the same as the epitope bound by the antibody described in Table 11a. In still other embodiments, the antibody binds to a myostatin epitope with higher affinity at pH 7.4 than at pH 5.8, which is the same as the myostatin epitope bound by the antibody described in Table 11a. In still other embodiments, the antibody binds to an epitope with higher affinity at pH 7.4 than at pH 5.8, which is the same as the epitope bound by the antibody comprising the VH and VL pair described in Table 11a. In some additional embodiments, the myostatin antibody binds to an epitope with higher affinity at neutral pH than at acidic pH, which is the same as the epitope bound by the antibody described in Table 2a, 11a or 13. In still other embodiments, the antibody binds to a myostatin epitope with higher affinity at pH 7.4 than at pH 5.8, which is the same as the myostatin epitope bound by the antibody described in Table 2a, 11a or 13.In still other embodiments, the antibody binds to the epitope with higher affinity at pH 7.4 than at pH 5.8, and the epitope is the same as the epitope bound by the antibody comprising the VH and VL pairs described in Table 2a, 11a or 13. In some embodiments, the isolated anti - myostatin antibody of the invention competes with the antibodies provided herein for binding to latent myostatin. In some embodiments, the isolated anti - myostatin antibody of the invention competes with the antibodies described in Table 13 for binding to latent myostatin. In some embodiments, the isolated anti - myostatin antibody of the invention competes with the antibodies comprising the VH and VL pairs described in Table 13 for binding to latent myostatin. In some embodiments, the antibody competes with the antibodies described in Table 2a for binding to latent myostatin. In some embodiments, the isolated anti - myostatin antibody of the invention competes with the antibodies comprising the VH and VL pairs described in Table 2a for binding to latent myostatin. In some embodiments, the antibody competes with the antibodies described in Table 11a for binding to latent myostatin. In some embodiments, the isolated anti - myostatin antibody of the invention competes with the antibodies comprising the VH and VL pairs described in Table 11a for binding to latent myostatin. In some additional embodiments, the anti - myostatin antibody competes with the antibodies described in Table 2a, 11a or 13 for binding to latent myostatin. In some additional embodiments, the anti - myostatin antibody competes with the antibodies comprising the VH and VL pairs described in Table 2a, 11a or 13 for binding to latent myostatin. In still other embodiments, the anti - myostatin antibody binds to latent myostatin with higher affinity at neutral pH than at acidic pH. In still other embodiments, the anti - myostatin antibody binds to latent myostatin with higher affinity at pH 7.4 than at pH 5.8. In still other embodiments, the anti - myostatin antibody binds to the polypeptide fragment consisting of amino acids 21 - 100 of the pro - myostatin peptide (SEQ ID NO: 78) with higher affinity at pH 7.4 than at pH 5.8. Methods for assessing the ability of an antibody to compete with a reference antibody for binding to latent myostatin are described herein and are well known in the art. In some embodiments, the isolated anti - myostatin antibody of the invention is a monoclonal antibody. In some embodiments, the isolated anti - myostatin antibody of the invention is a human, humanized or chimeric antibody. In some embodiments, the isolated anti - myostatin antibody of the invention is an antibody fragment that binds to myostatin. In some embodiments, the isolated anti - myostatin antibody of the invention is an antibody fragment that binds to latent myostatin. In some embodiments, the isolated anti - myostatin antibody of the invention is an antibody fragment that binds to the polypeptide fragment consisting of amino acids 21 - 100 of the pro - myostatin peptide (SEQ ID NO: 78). In some embodiments, the isolated anti - myostatin antibody of the invention is a full - length IgG antibody. In some embodiments, the myostatin antibodies of the present invention include: (a) (i) HVR-H3, comprising the amino acid sequence GVPAX 1SX 2GGDX 3, wherein X 1 is Y or H, X 2 is T or H, X 3 is L or K (SEQ ID NO: 128); (ii) HVR-L3, comprising the amino acid sequence AGGYGGGX 1YA, wherein X 1 is L or R (SEQ ID NO: 131); and (iii) HVR-H2, comprising the amino acid sequence IISX 1AGX 2X 3YX 4X 5X 6WAKX 7, wherein X 1 is Y or H, X 2 is S or K, X 3 is T, M or K, X 4 is Y or K, X 5 is A, M or E, X 6 is S or E, X 7 is G or K (SEQ ID NO: 127); (b) (i) HVR-H1, comprising the amino acid sequence X 1X 2DIS, wherein X 1 is S or H, X 2 is Y, T, D or E (SEQ ID NO: 126); (ii) HVR-H2, comprising the amino acid sequence IISX 1AGX 2X 3YX 4X 5X 6WAKX 7, wherein X 1 is Y or H, X 2 is S or K, X 3 is T, M or K, X 4 is Y or K, X 5 is A, M or E, X 6 is S or E, X 7 is G or K (Sequence ID: 127); and (iii) HVR-H3, including the amino acid sequence GVPAX 1SX 2GGDX 3, where X 1 is Y or H, X 2 is T or H, X 3 is L or K (Sequence ID: 128); (c) (i) HVR-H1, including the amino acid sequence X 1X 2DIS, where X 1 is S or H, X 2 is Y, T, D or E (Sequence ID: 126); (ii) HVR-H2, including the amino acid sequence IISX 1AGX 2X 3YX 4X 5X 6WAKX 7, where X 1 is Y or H, X 2 is S or K, X 3 is T, M or K, X 4 is Y or K, X 5 is A, M or E, X 6 is S or E, X 7 is G or K (Sequence ID: 127); (iii) HVR-H3, including the amino acid sequence GVPAX 1SX 2GGDX 3, where X 1 is Y or H, X 2 is T or H, X 3 is L or K (Sequence ID: 128); (iv) HVR-L1, including the amino acid sequence X 1X 2SQX 3VX 4X 5X 6NWLS, where X 1 is Q or T, X 2 is S or T, X 3 is S or E, X 4 is Y or F, X 5 is D or H, X 6 is N, D, A or E (Sequence ID: 129); (v) HVR-L2, including the amino acid sequence WAX 1TLAX 2, where X 1 is S or E, X 2 is S, Y, F or W (Sequence ID: 130); and (vi) HVR-L3, including the amino acid sequence AGGYGGGX 1YA, where X 1 is L or R (Sequence ID: 131); (d) (i) HVR-L1, including the amino acid sequence X 1X 2SQX 3VX 4X 5X 6NWLS, where X 1 is Q or T, X 2 is S or T, X 3 is S or E, X 4 is Y or F, X 5 is D or H, X 6 is N, D, A or E (Sequence ID: 129); (ii) HVR-L2, including the amino acid sequence WAX 1TLAX 2, where X 1 is S or E, X 2 is S, Y, F or W (Sequence ID: 130); and (iii) HVR-L3, including the amino acid sequence AGGYGGGX 1YA, where X 1 is L or R (Sequence ID No.: 131). In some embodiments, the antibody of (b) further comprises a heavy chain variable domain framework FR1, comprising the amino acid sequence of any one of Sequence ID Nos.: 132-134; FR2, comprising the amino acid sequence of any one of Sequence ID Nos.: 135-136; FR3, comprising the amino acid sequence of Sequence ID No.: 137; and FR4, comprising the amino acid sequence of Sequence ID No.: 138. In some embodiments, the antibody of (d) further comprises a light chain variable domain framework FR1, comprising the amino acid sequence of Sequence ID No.: 139; FR2, comprising the amino acid sequence of any one of Sequence ID Nos.: 140-141; FR3, comprising the amino acid sequence of any one of Sequence ID Nos.: 142-143; and FR4, comprising the amino acid sequence of Sequence ID No.: 144. In some embodiments, the isolated myostatin antibody of the present invention comprises: (a) HVR-H3, comprising the amino acid sequence GVPAX 1SX 2GGDX 3, wherein X 1 is Y or H, X 2 is T or H, X 3 is L or K (Sequence ID No.: 128); (b) HVR-L3, comprising the amino acid sequence AGGYGGGX 1YA, wherein X 1 is L or R (Sequence ID No.: 131); and (c) HVR-H2, comprising the amino acid sequence IISX 1AGX 2X 3YX 4X 5X 6WAKX 7, wherein X 1 is Y or H, X 2 is S or K, X 3 is T, M or K, X 4 is Y or K, X 5 is A, M or E, X 6 is S or E, X 7 is G or K (Sequence ID No.: 127). In some embodiments, the isolated myostatin antibody of the present invention comprises: (a) HVR-H1, comprising the amino acid sequence X 1X 2DIS, wherein X 1 is S or H, X 2 is Y, T, D or E (SEQ ID NO: 126); (b) HVR-H2, comprising the amino acid sequence IISX 1AGX 2X 3YX 4X 5X 6WAKX 7, wherein X 1 is Y or H, X 2 is S or K, X 3 is T, M or K, X 4 is Y or K, X 5 is A, M or E, X 6 is S or E, X 7 is G or K (SEQ ID NO: 127); and (c) HVR-H3, comprising the amino acid sequence GVPAX 1SX 2GGDX 3, wherein X 1 is Y or H, X 2 is T or H, X 3 is L or K (SEQ ID NO: 128). In yet other embodiments, the antibody comprises a heavy chain variable domain framework FR1, comprising an amino acid sequence of any one of SEQ ID NOs: 132-134; FR2, comprising an amino acid sequence of any one of SEQ ID NOs: 135-136; FR3, comprising the amino acid sequence of SEQ ID NO: 137; and FR4, comprising the amino acid sequence of SEQ ID NO: 138. In yet other embodiments, the antibody additionally comprises: (a) HVR-L1, comprising the amino acid sequence X 1X 2SQX 3VX 4X 5X 6NWLS, wherein X 1 is Q or T, X 2 is S or T, X 3 is S or E, X 4 is Y or F, X 5 is D or H, X 6 is N, D, A or E (SEQ ID NO: 129); (b) HVR-L2, comprising the amino acid sequence WAX 1TLAX 2, wherein X 1 is S or E, X 2 is S, Y, F or W (SEQ ID NO: 130); and (c) HVR-L3, comprising the amino acid sequence AGGYGGGX 1YA, wherein X 1 is L or R (SEQ ID NO: 131). In some embodiments, the isolated myostatin antibody of the invention comprises: (a) HVR-L1, comprising the amino acid sequence X 1X 2SQX 3VX 4X 5X 6NWLS, wherein X 1 is Q or T, X 2 is S or T, X 3 is S or E, X 4 is Y or F, X 5 is D or H, X 6 is N, D, A or E (SEQ ID NO: 129); (b) HVR-L2, comprising the amino acid sequence WAX 1TLAX 2, wherein X 1 is S or E, X 2 is S, Y, F or W (SEQ ID NO: 130); and (c) HVR-L3, comprising the amino acid sequence AGGYGGGX 1YA, wherein X 1 is L or R (SEQ ID NO: 131). In still other embodiments, the antibody further comprises: a light chain variable domain framework FR1, comprising the amino acid sequence of SEQ ID NO: 139; FR2, comprising any one of the amino acid sequences of SEQ ID NOs: 140-141; FR3, comprising any one of the amino acid sequences of SEQ ID NOs: 142-143; and FR4, comprising the amino acid sequence of SEQ ID NO: 144. In some embodiments, the isolated myostatin antibody of the present invention includes: a heavy chain variable domain framework FR1, including the amino acid sequence of any one of SEQ ID NOs: 132-134; FR2, including the amino acid sequence of any one of SEQ ID NOs: 135-136; FR3, including the amino acid sequence of SEQ ID NO: 137; and FR4, including the amino acid sequence of SEQ ID NO: 138. In some embodiments, the isolated myostatin antibody of the present invention includes a light chain variable domain framework FR1, including the amino acid sequence of SEQ ID NO: 139; FR2, including the amino acid sequence of any one of SEQ ID NOs: 140-141; FR3, including the amino acid sequence of any one of SEQ ID NOs: 142-143; and FR4, including the amino acid sequence of SEQ ID NO: 144. In some embodiments, the isolated myostatin antibody of the present invention includes: (a) a VH sequence having at least 95% sequence identity with the amino acid sequence of any one of SEQ ID NOs: 13, 16-30, 32-34, and 86-95; (b) a VL sequence having at least 95% sequence identity with the amino acid sequence of any one of SEQ ID NOs: 15, 31, 35-38, and 96-99; or (c) the VH sequence as described in (a) and the VL sequence as described in (b). In still other embodiments, the antibody includes a VH sequence of any one of SEQ ID NOs: 13, 16-30, 32-34, and 86-95. In still other embodiments, the antibody includes a VL sequence of any one of SEQ ID NOs: 15, 31, 35-38, and 96-99. In some embodiments, the antibody includes a VH sequence of any one of SEQ ID NOs: 13, 16-30, 32-34, and 86-95. In still other embodiments, the antibody includes a VH sequence of any one of SEQ ID NOs: 13, 16-30, 32-34, and 86-95; and a VL sequence of any one of SEQ ID NOs: 15, 31, 35-38, and 96-99. The present invention also provides an isolated nucleic acid encoding the myostatin antibody of the present invention. The present invention also provides a host cell comprising the nucleic acid of the present invention. The present invention also provides a method for manufacturing an antibody, including culturing the host cell of the present invention such that the antibody is manufactured. In some aspects, the present invention provides a method for manufacturing a myostatin antibody, including: (a) culturing the host cell of the present invention such that the antibody is manufactured; or (b) immunizing an animal with a polypeptide, wherein the polypeptide includes a region corresponding to the amino acids at positions 21-100 of the pro-myostatin peptide (SEQ ID NO: 78). The present invention further provides a method for manufacturing a myostatin antibody. In some embodiments, the method includes immunizing an animal with a polypeptide, wherein the polypeptide includes a region corresponding to the amino acids at positions 21-100 of the pro-myostatin peptide (SEQ ID NO: 78). The present invention also provides a pharmaceutical formulation comprising the myostatin antibody of the present invention and a pharmaceutically acceptable carrier. The myostatin antibody of the present invention can be used as a medicament. In some embodiments, the antibody is used to manufacture a medicament for the following uses: (a) treating muscle atrophy diseases; (b) increasing the mass of muscle tissue; (c) increasing the strength of muscle tissue; or (d) reducing the accumulation of body fat. In some embodiments, the myostatin antibody of the present invention can be used to treat muscle atrophy diseases. The myostatin antibody of the present invention can be used to increase the mass of muscle tissue. The myostatin antibody of the present invention can be used to increase the strength of muscle tissue. The myostatin antibody of the present invention can be used to reduce the accumulation of body fat. In some embodiments, the myostatin antibody provided herein has the use of (a) treating muscle atrophy diseases; (b) increasing the mass of muscle tissue; (c) increasing the strength of muscle tissue; or (d) reducing the accumulation of body fat. The myostatin antibody of the present invention can be used to manufacture a medicament. In some embodiments, the antibody is used to manufacture a medicament for: (a) treating muscle atrophy diseases; (b) increasing the mass of muscle tissue; (c) increasing the strength of muscle tissue; or (d) reducing the accumulation of body fat. In some embodiments, this medicament is used to treat muscle atrophy diseases. In some embodiments, this medicament is used to increase the mass of muscle tissue. In some embodiments, this medicament is used to increase the strength of muscle tissue. In some embodiments, this medicament is used to reduce the accumulation of body fat. The present invention also provides a method for treating an individual with a muscle atrophy disease. In some embodiments, the method comprises administering to the individual an effective amount of the myostatin antibody of the present invention. The present invention also provides a method for increasing the mass of muscle tissue in an individual. In some embodiments, the method comprises administering to the individual an effective amount of the myostatin antibody of the present invention to increase the mass of muscle tissue. The present invention also provides a method for increasing the strength of muscle tissue in an individual. In some embodiments, the method comprises administering to the individual an effective amount of the myostatin antibody of the present invention to increase the strength of muscle tissue. The present invention also provides a method for reducing the accumulation of body fat in an individual. In some embodiments, the method comprises administering to the individual an effective amount of the myostatin antibody of the present invention to reduce the accumulation of body fat. The present invention provides polypeptides comprising a variant Fc region and methods for their manufacture and use. In one embodiment, the present invention provides an FcγRIIB-binding polypeptide comprising a variant Fc region and methods of using the same. In some embodiments, the variant Fc region of the present invention having enhanced FcγRIIB-binding activity comprises at least one amino acid alteration in the parent Fc region. In still other embodiments, the ratio of [KD value of the parent Fc region for monkey FcγRIIb] / [KD value of the variant Fc region for monkey FcγRIIb] is 2 or greater. In still other embodiments, the ratio of [KD value of the parent Fc region for monkey FcγRIIIa] / [KD value of the variant Fc region for monkey FcγRIIIa] is 0.5 or less. In still other embodiments, the ratio of [KD value of the parent Fc region for human FcγRIIb] / [KD value of the variant Fc region for human FcγRIIb] is 2 or greater. In still other embodiments, the ratio of [KD value of the parent Fc region for human FcγRIIIa] / [KD value of the variant Fc region for human FcγRIIIa] is 0.5 or less. In still other embodiments, the ratio of [KD value of the parent Fc region for human FcγRIIa (H type)] / [KD value of the variant Fc region for human FcγRIIa (H type)] is 5.0 or less. In still other embodiments, the ratio of [KD value of the parent Fc region for human FcγRIIa (R type)] / [KD value of the variant Fc region for human FcγRIIa (R type)] is 5.0 or less. In another embodiment, the KD value of the variant Fc region for monkey FcγRIIb is 1.0×10 -6 M or less. In another embodiment, the KD value of the variant Fc region for monkey FcγRIIIa is 5.0×10 -7 M or greater. In another example, the KD value of the variant Fc region for human FcγRIIb is 2.0×10 -6 M or less. In another embodiment, the KD value of the variant Fc region for human FcγRIIIa is 1.0×10 -6 M or greater. In another embodiment, the KD value of the variant Fc region for human FcγRIIa (H type) is 1.0×10 -7 M or greater. In another embodiment, the KD value of the variant Fc region for human FcγRIIa (R type) is 2.0×10 -7 M or greater. In some embodiments, the variant Fc region of the present invention having enhanced FcγRIIb binding activity comprises at least one amino acid modification at at least one position selected from the group consisting of: 231, 232, 233, 234, 235, 236, 237, 238, 239, 264, 266, 267, 268, 271, 295, 298, 325, 326, 327, 328, 330, 331, 332, 334, and 396 (according to EU numbering). In yet other embodiments, the variant Fc region having enhanced FcγRIIb binding activity comprises at least two amino acid modifications, including: (a) an amino acid modification at position 236; and (b) at least one amino acid modification at at least one position selected from: (i) positions 231, 232, 233, 234, 235, 237, 238, 239, 264, 266, 267, 268, 271, 295, 298, 325, 326, 327, 328, 330, 331, 332, 334, and 396; (ii) positions 231, 232, 235, 239, 268, 295, 298, 326, 330, and 396; or (iii) positions 268, 295, 326, and 330 (according to EU numbering). In yet other embodiments, the variant Fc region having enhanced FcγRIIb binding activity comprises at least two amino acid modifications, including: (a) an amino acid modification at position 236; and (b) at least one amino acid modification at at least one position selected from the group consisting of: 231, 232, 233, 234, 235, 237, 238, 239, 264, 266, 267, 268, 271, 295, 298, 325, 326, 327, 328, 330, 331, 332, 334, and 396 (according to EU numbering). In yet other embodiments, the variant Fc region having enhanced FcγRIIb binding activity comprises at least two amino acid modifications, including: (a) an amino acid modification at position 236; and (b) at least one amino acid modification at at least one position selected from the group consisting of: 231, 232, 235, 239, 268, 295, 298, 326, 330, and 396 (according to EU numbering). In yet other embodiments, the variant Fc region having enhanced FcγRIIb binding activity comprises at least two amino acid modifications, including: (a) an amino acid modification at position 236; and (b) at least one amino acid modification at at least one position selected from the group consisting of: 268, 295, 326, and 330 (according to EU numbering). In some embodiments, the variant Fc region of the present invention having enhanced FcγRIIb binding activity includes at least one amino acid selected from the group consisting of: (a) Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, Trp, Tyr at position 231; (b) Ala, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, Trp, Tyr at position 232; (c) Asp at position 233; (d) Trp, Tyr at position 234; (e) Trp at position 235; (f) Ala, Asp, Glu, His, Ile, Leu, Met, Asn, Gln, Ser, Thr, Val at position 236; (g) Asp, Tyr at position 237; (h) Glu, Ile, Met, Gln, Tyr at position 238; (i) Ile, Leu, Asn, Pro, Val at position 239; (j) Ile at position 264; (k) Phe at position 266; (l) Ala, His, Leu at position 267; (m) Asp, Glu at position 268; (n) Asp, Glu, Gly at position 271; (o) Leu at position 295; (p) Leu at position 298; (q) Glu, Phe, Ile, Leu at position 325; (r) Thr at position 326; (s) Ile, Asn at position 327; (t) Thr at position 328; (u) Lys, Arg at position 330; (v) Glu at position 331; (w) Asp at position 332; (x) Asp, Ile, Met, Val, Tyr at position 334; and (y) Ala, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, Trp, Tyr at position 396 (according to EU numbering). In still other embodiments, the variant Fc region having enhanced FcγRIIb binding activity includes at least one amino acid selected from the group consisting of: (a) Gly, Thr at position 231; (b) Asp at position 232; (c) Trp at position 235; (d) Asn, Thr at position 236; (e) Val at position 239; (f) Asp, Glu at position 268; (g) Leu at position 295; (h) Leu at position 298; (i) Thr at position 326; (j) Lys, Arg at position 330; and (k) Lys, Met at position 396 (according to EU numbering). In another embodiment, the present invention provides a polypeptide comprising a variant Fc region with an increased isoelectric point (pI) and methods of using the same. In some embodiments, the polypeptide comprising a variant Fc region with an increased pI comprises at least two amino acid modifications to the parental Fc region. In still other embodiments, each amino acid modification increases the isoelectric point of the variant Fc region compared to the isoelectric point (pI) of the parental Fc region. In still other embodiments, the amino acids may be exposed on the surface of the variant Fc region. In still other embodiments, the polypeptide comprises a variant Fc region and an antigen-binding domain. In still other embodiments, the antigen-binding activity of the antigen-binding domain changes according to ionic concentration conditions. In still other embodiments, the variant Fc region of the present invention having an increased pI comprises at least two amino acid modifications at at least two positions selected from the group consisting of: 285, 311, 312, 315, 318, 333, 335, 337, 341, 342, 343, 384, 385, 388, 390, 399, 400, 401, 402, 413, 420, 422, and 431 (according to EU numbering). In still other embodiments, the variant Fc region having an increased pI comprises Arg or Lys at each selected position. In some embodiments, the variant Fc region of the present invention comprises the amino acid modifications as described in Table 14-30. In some embodiments, the polypeptide comprises the variant Fc region of the present invention. In still other embodiments, the parental Fc region is derived from human IgG1. In still other embodiments, the polypeptide is an antibody. In still other embodiments, the polypeptide is an Fc fusion protein. The present invention provides a polypeptide comprising any one of the amino acid sequences of SEQ ID NOs: 229-381. The present invention also provides a isolated nucleic acid encoding a polypeptide comprising the variant Fc region of the present invention. The present invention also provides a host cell comprising the nucleic acid of the present invention. The present invention also provides a method of manufacturing a polypeptide comprising a variant Fc region, comprising culturing the host cell of the present invention such that the polypeptide is produced. The present invention further provides a pharmaceutical formulation comprising a polypeptide comprising the variant Fc region of the present invention and a pharmaceutically acceptable carrier. The techniques or procedures described or cited herein are generally traditional methods well-known and commonly used by those skilled in the art. For example, by way of illustration, such as Sambrook et al., Molecular Cloning: A Laboratory Manual 3d edition (2001) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.; Current Protocols in Molecular Biology (edited by F.M. Ausubel et al. (2003)); the series Methods in Enzymology (Academic Press, Inc.): PCR 2: A Practical Approach (edited by M.J. MacPherson, B.D. Hames and G.R. Taylor (1995)), Harlow and Lane (1988) Antibodies, A Laboratory Manual, and Animal Cell Culture (edited by R.I. Freshney, (1987)); Oligonucleotide Synthesis (edited by M.J. Gait, 1984); Methods in Molecular Biology, Humana Press; Cell Biology: A Laboratory Notebook (edited by J.E. Cellis, 1998) Academic Press; Animal Cell Culture (edited by R.I. Freshney, 1987); Introduction to Cell and Tissue Culture (J.P. Mather and P.E. Roberts, 1998) Plenum Press; Cell and Tissue Culture: Laboratory Procedures (edited by A. Doyle, J.B. Griffiths and D.G. Newell, 1993 - 8) J. Wiley and Sons; Handbook of Experimental Immunology (edited by D.M. Weir and C.C. Blackwell); Gene Transfer Vectors for Mammalian Cells (J.M.Methods widely used as described in Miller and M.P. Calos, eds., 1987); PCR: The Polymerase Chain Reaction, (Mullis et al., eds., 1994); Current Protocols in Immunology (J.E. Coligan et al., eds., 1991); Short Protocols in Molecular Biology (Wiley & Sons, 1999); Immunobiology (C.A. Janeway and P. Travers, 1997); Antibodies (P. Finch, 1997); Antibodies: A Practical Approach (D. Catty, ed., IRL Press, 1988-1989); Monoclonal Antibodies: A Practical Approach (P. Shepherd and C. Dean, eds., Oxford University Press, 2000); Using Antibodies: A Laboratory Manual (E. Harlow and D. Lane (Cold Spring Harbor Laboratory Press, 1999); The Antibodies (M. Zanetti and J.D. Capra, eds., Harwood Academic Publishers, 1995); and Cancer: Principles and Practice of Oncology (V.T. DeVita et al., eds., J.B. Lippincott Company, 1993). I. Definitions. Unless otherwise defined, the technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this invention belongs. Singleton et al., Dictionary of Microbiology and Molecular Biology 2nd ed., J. Wiley & Sons (New York, N.Y. 1994) and March, Advanced Organic Chemistry Reactions, Mechanisms and Structure 4th ed., John Wiley & Sons (New York, N.Y. 1992) provide general guidance to one of ordinary skill in the art for many of the terms used in this application. The documents cited herein, including patent applications and publications, are hereby incorporated by reference in their entirety. To explain this specification, the following definitions will be used, and where appropriate, terms used in the singular may also include the plural and vice versa. It should be understood that the terms used herein are only for the purpose of describing specific embodiments and are not intended to be limiting. In the event of any conflict between any of the following definitions and any document incorporated by reference herein, the following definitions will prevail. "Acceptor human framework" for the purposes herein is a framework comprising an amino acid sequence of a light chain variable domain (VL) framework or a heavy chain variable domain (VH) framework that is derived from a human immunoglobulin framework or a human consensus framework as defined below. An acceptor human framework "derived from" a human immunoglobulin framework or a human consensus framework may include the same amino acid sequence thereof, or it may contain amino acid sequence alterations. In some embodiments, the number of amino acid alterations is 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, or 2 or fewer. In some embodiments, the VL acceptor human framework is identical in sequence to a VL human immunoglobulin framework sequence or a human consensus framework sequence. "Affinity" refers to the total strength of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless otherwise stated, "binding affinity" as used herein refers to the intrinsic binding affinity, which reflects the 1:1 interaction between the members of a binding pair (e.g., an antibody and an antigen). The affinity of molecule X for its partner Y can generally be expressed by the dissociation constant (Kd). Affinity can be measured by methods known in the art, including those described herein. Specific descriptions and exemplary embodiments for measuring binding affinity will be described below. An "affinity matured" antibody refers to an antibody that has one or more alterations in one or more hypervariable regions (HVRs) compared to a parent antibody that does not have such alterations, where such alterations result in an improvement in the affinity of the antibody for an antigen. The terms "anti - myostatin antibody" and "antibody that binds to myostatin" refer to an antibody that is capable of binding to myostatin with sufficient affinity such that the antibody can be used as a diagnostic and / or therapeutic agent in targeting myostatin. In one embodiment, for example, as measured by radioimmunoassay (RIA), the degree to which the anti - myostatin antibody binds to an irrelevant non - myostatin protein is less than about 10% of the binding of the antibody to myostatin. In certain embodiments, the antibody that binds to myostatin has a dissociation constant (Kd) of ≤1 μM, ≤100 nM, ≤10 nM, ≤1 nM, ≤0.1 nM, ≤0.01 nM, or ≤0.001 nM (e.g., 10 -8 M or less, e.g., from 10 -8 M to 10 -13 M, e.g., from 10 -9 M to 10 -13 M). In certain embodiments, the anti - myostatin antibody binds to an epitope of myostatin that is conserved among myostatins from different species. The term "antibody" is used herein in the broadest sense and encompasses a variety of antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, so long as they exhibit the desired antigen - binding activity. "Antibody fragment" refers to a molecule other than an intact antibody that includes a portion of the intact antibody and binds the antigen to which the intact antibody binds. Examples of antibody fragments include but are not limited to Fv, Fab, Fab’, Fab’ - SH, F(ab’) 2; diabody; linear antibody; single - chain antibody molecule (e.g., scFv); and multispecific antibodies formed from antibody fragments. "Antibodies that bind the same epitope" as a reference antibody refers to an antibody that blocks the binding of the reference antibody to its antigen in a competition assay, and / or conversely, the reference antibody blocks the binding of the antibody to its antigen in a competition assay. Exemplary competition assays are provided herein. The term "chimeric" antibody refers to an antibody in which portions of the heavy and / or light chains are from a particular source or species and the remaining portions of the heavy and / or light chains are from a different source or species. The "class" of an antibody refers to the type of constant domain or constant region possessed by its heavy chain. There are five main classes of antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these classes can be further divided into subgroups (isotypes), e.g., IgG 1, IgG 2, IgG 3, IgG 4, IgA 1 and IgA 2. The constant domains of the heavy chains corresponding to the different classes of immunoglobulins are designated α, δ, ε, γ, and μ, respectively. As used herein, the term "cytotoxic agent" refers to a substance that inhibits or arrests the function of cells and / or causes cell death or destruction. Cytotoxic agents include, but are not limited to, radioactive isotopes (e.g., At 211 、I 131 、I 125 、Y 90 、Re 186 、Re 188 、Sm 153 、Bi 212 、P 32 、Pb 212and radioisotopes of Lu); chemotherapeutic agents or drugs (e.g., methotrexate, adriamicin, vinca alkaloids (vincristine, vinblastine, etoposide), doxorubicin, melphalan, mitomycin C, chlorambucil, daunorubicin or other intercalating agents); growth inhibitors; enzymes and fragments thereof, such as lysozyme; antibiotics; toxins, such as small molecule toxins or enzymatically active toxins of bacterial, fungal, plant or animal origin, including fragments and / or variants thereof; and various anti-tumor or anti-cancer agents disclosed below. "Effector function" refers to those biological activities attributable to the Fc region of an antibody, which vary with antibody isotype. Examples of antibody effector functions include: Clq binding and complement dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; negative regulation of cell surface receptors (e.g., B cell receptors); and B cell activation. An "effective amount" of a reagent, such as a pharmaceutical formulation, is an amount that is effective to achieve a desired therapeutic or prophylactic result at a dosage and for a time period required. The term "epitope" includes any determinant capable of being bound by an antibody. An epitope is the region of an antigen that is bound by an antibody that targets the antigen and includes specific amino acids that directly contact the antibody. Epitope determinants can include chemical reactive surface clusters of molecules (e.g., amino acids, sugar side chains, phosphate groups or sulfonyl groups) and can have specific three-dimensional structural characteristics, and / or specific charge characteristics. Generally, an antibody specific for a particular target antigen will preferentially recognize an epitope on the target antigen in a complex mixture of proteins and / or macromolecules. "Fc receptor" or "FcR" describes a receptor that binds to the Fc region of an antibody. In some embodiments, the FcR is a native human FcR. In some embodiments, the FcR is a receptor that binds to an IgG antibody (gamma receptor) and includes receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternatively spliced forms of these receptors. The FcγRII receptor includes FcγRIIA ("activating receptor") and FcγRIIB ("inhibitory receptor"), which have similar amino acid sequences and differ mainly in their cytoplasmic domains. The activating receptor FcγRIIA contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. The inhibitory receptor FcγRIIB contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain (see, e.g., Daëron , Annu. Rev. Immunol. 15:203-234 (1997)). FcRs have been reviewed in, e.g., Ravetch and Kinet, Annu. Rev. Immunol. 9:457-92 (1991); Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J. Lab. Clin. Med. 126:330-41 (1995). Other FcRs, including those yet to be identified, are encompassed by the term "FcR" herein. The term "Fc receptor" or "FcR" also includes the neonatal receptor, FcRn, which is responsible for the transfer of maternal IgG to the fetus (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994)) and the constant regulation of immunoglobulins. Methods for measuring binding to FcRn are known (see, e.g., Ghetie and Ward, Immunol. Today 18(12):592-598 (1997); Ghetie et al., Nature Biotechnology 15(7):637-640 (1997); Hinton et al., J. Biol. Chem. 279(8):6213-6216 (2004); WO 2004 / 92219 (Hinton et al.). Binding in vivo to human FcRn and the plasma half-life of polypeptides with high affinity for human FcRn can be analyzed, e.g., in transgenic mice or human cell lines transfected to express human FcRn, or in primates administered polypeptides with variant Fc regions. WO 2000 / 42072 (Presta) describes antibody variants with improved or reduced binding to FcR. See also, e.g., Shields et al., J. Biol. Chem. 9(2):6591-6604 (2001). As used herein, the term "Fc region" is used to define the C-terminal region of an immunoglobulin heavy chain that includes at least a portion of the constant region. This term includes native sequence Fc regions and variant Fc regions. In one embodiment, the human IgG heavy chain Fc region extends from Cys226 or from Pro230 to the carboxyl terminus of the heavy chain. However, the C-terminal lysine (Lys447) or glycine-lysine (Gly446-Lys447) of the Fc region may or may not be present. Unless otherwise specified herein, the numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also known as the EU index, as described by Kabat et al., Sequences of Proteins of Immunological Interest 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991. The term "antibody comprising an Fc region" refers to an antibody that includes an Fc region. The C-terminal lysine (residue 477, according to the EU numbering system) or C-terminal glycine-lysine (residues 446-447) of the Fc region may be removed, e.g., during antibody purification or by recombinant engineering of the nucleic acid encoding the antibody. Thus, compositions comprising the antibodies of the invention that have an Fc region may include antibodies with G446-K447, antibodies with G446 and without K447, antibodies with all G446-K447 removed, or mixtures of the three types of antibodies. "Framework" or "FR" refers to the variable domain residues other than the hypervariable region (HVR) residues. The FR of the variable domain generally consists of four FR domains: FR1, FR2, FR3, and FR4. Thus, the HVR and FR sequences generally occur in VH (or VL) in the following order: FR1-H1(L1)-FR2-H2(L2)-FR3-H3(L3)-FR4. The terms "full-length antibody", "intact antibody", and "whole antibody" are used interchangeably herein and refer to an antibody having a structure substantially similar to the structure of a natural antibody or having a heavy chain that includes an Fc region as defined herein. A "functional Fc region" has the "effector functions" of a native sequence Fc region. Exemplary "effector functions" include Clq binding; CDC; Fc receptor binding; ADCC; phagocytosis; negative regulation of cell surface receptors (e.g., B cell receptors), etc. Such effector functions generally require the Fc region to be associated with a binding domain (e.g., an antibody variable domain) and can be assessed using a variety of disclosed assays, e.g., as defined herein. The terms "host cell", "host cell line", and "host cell culture" are used interchangeably and refer to a cell into which exogenous nucleic acid has been introduced, including progeny of such a cell. Host cells include "transformants" and "transformed cells", which include the original transformed cell and progeny derived therefrom, without regard to the number of passages. The nucleic acid content of the progeny may not be identical to that of the parental cell and may include mutations. Mutant progeny having the same functionality or biological activity as that screened or selected in the original transformed cell are included herein. A "human antibody" is one having an amino acid sequence corresponding to an antibody produced by a human or human cell or derived from a non-human source, the amino acid sequence of which has been modified using a human antibody library or other human antibody-encoding sequences. This definition of a human antibody specifically excludes humanized antibodies that include non-human antigen-binding residues. "Human consensus framework" is a framework that represents the amino acid residues that occur most frequently in a selection of human immunoglobulin VL or VH framework sequences. Generally, the selection of human immunoglobulin VL or VH sequences is from subtypes of variable domain sequences. Typically, the subtypes of the sequences are those of Kabat et al., Sequences of Proteins of Immunological Interest, Fifth Edition, NIH Publication 91-3242, Bethesda MD (1991), vols. 1-3. In one embodiment, for VL, the subtype is as described by Kabat et al., Subtype kappa I in supra. In one embodiment, for VH, the subtype is as Kabat et al., subtype III in supra. A "humanized" antibody refers to a chimeric antibody that includes amino acid residues from non-human HVRs and amino acid residues from human FRs. In certain embodiments, a humanized antibody will include at least one and typically two variable domains substantially in their entirety, wherein all or substantially all of the HVRs (e.g., CDRs) correspond to those of a non-human antibody and all or substantially all of the FRs correspond to those of a human antibody. A humanized antibody optionally includes at least a portion of an antibody constant region derived from a human antibody. A "humanized form" of an antibody (e.g., a non-human antibody) refers to an antibody that has been humanized. As used herein, the term "hypervariable region" or "HVR" refers to each region of an antibody variable domain that is hypervariable in sequence ("complementary determining region" or "CDR"), and / or forms a structurally defined loop ("hypervariable loop"), and / or contains antigen contact residues ("antigen contact"). Generally, an antibody includes six HVRs: three in VH (H1, H2, H3) and three in VL (L1, L2, L3). Exemplary HVRs herein include: (a) hypervariable loops occurring at amino acid residues 26-32 (L1), 50-52 (L2), 91-96 (L3), 26-32 (Hl), 53-55 (H2), and 96-101 (H3) (Chothia, J. Mol. Biol. 196:901-917 (1987)); (b) CDRs occurring at amino acid residues 24-34 (L1), 50-56 (L2), 89-97 (L3), 31-35b (H1), 50-65 (H2), and 95-102 (H3) (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, NIH, Bethesda, MD (1991)); (c) hypervariable loops occurring at amino acid residues 27c-36 (L1), 46-55 (L2), 89-96 (L3), 30-35b (H1), 47-58 (H2), and 93-101 (H3) (MacCallum et al., antigen contact of J. Mol. Biol. 262:732-745 (1996)); and (d) a combination of (a), (b) and / or (c), comprising HVR amino acid residues 46-56 (L2), 47-56 (L2), 48-56 (L2), 49-56 (L2), 26-35 (H1), 26-35b (H1), 49-65 (H2), 93-102 (H3), and 94-102 (H3). Unless otherwise specified, HVR residues and other residues in the variable domain (e.g., FR residues) herein are numbered according to Kabat et al., supra. An "immunoconjugate" is an antibody conjugated to one or more heterogeneous molecules, including but not limited to cytotoxic agents. An "individual" or "subject" is a mammal. Mammals include but are not limited to domesticated animals (e.g., cows, sheep, cats, dogs, and horses), primates (e.g., humans and non-human primates such as monkeys), rabbits, and rodents (e.g., mice and rats). In certain embodiments, the individual or subject is human. A "purified" antibody is an antibody that has been separated from the components of its natural environment. In some embodiments, the antibody is purified to greater than 95% or 99% purity, as determined by, for example, electrophoretic (e.g., SDS-PAGE, isoelectric focusing (IEF), capillary electrophoresis) or chromatographic (e.g., ion exchange or reverse phase HPLC) methods. A review of methods for assessing antibody purity can be found, for example, in Flatman et al., J. Chromatogr. B 848:79-87 (2007). A "purified" nucleic acid refers to a nucleic acid molecule that has been separated from the components of its natural environment. Purified nucleic acids include nucleic acid molecules contained in cells that normally contain the nucleic acid molecule, but the nucleic acid molecule is present extrachromosomally or at a chromosomal location different from its natural chromosomal location. A "purified nucleic acid encoding an anti-myostatin antibody" refers to one or more nucleic acid molecules encoding the heavy and light chains (or fragments thereof) of the antibody, such nucleic acid molecules contained in a single vector or separate vectors, and such nucleic acid molecules present at one or more locations in a host cell. As used herein, the term "monoclonal antibody" refers to an antibody obtained from a substantially homogeneous population of antibodies, i.e., antibodies that include the same population and / or individual antibodies that bind to the same antigenic determinant, except for, e.g., antibodies that contain naturally occurring mutations or variant antibodies that may occur during the production of the monoclonal antibody preparation (such variant antibodies are typically present in minor amounts). Different from the preparation of polyclonal antibodies, which usually contain different antibodies against different epitopes (antigenic determinants), each monoclonal antibody in a monoclonal antibody preparation is directed against a single epitope on an antigen. Thus, the modifier "monoclonal" refers to the antibody characteristic of being obtained from a substantially homogeneous population of antibodies and is not to be construed as requiring that the antibody be produced by any particular method. For example, monoclonal antibodies to be used in accordance with the present invention can be prepared by a variety of techniques, including but not limited to hybridoma technology, recombinant DNA methods, phage display methods, and methods using transgenic animals that contain all or part of the human immunoglobulin loci. Such methods and other exemplary methods for making monoclonal antibodies will be described herein. A "naked antibody" refers to an antibody that is not conjugated to a heterologous moiety (e.g., a cytotoxic moiety) or a radiolabel. Naked antibodies can be present in pharmaceutical formulations. A "natural antibody" refers to naturally occurring immunoglobulin molecules having different structures. For example, a natural IgG antibody is a heterotetrameric glycoprotein of approximately 150,000 daltons, composed of two identical light chains and two identical heavy chains linked by disulfide bonds. From the N- to the C-terminus, each heavy chain has a variable region (VH), also known as the variable heavy chain domain or heavy chain variable domain, followed by three constant domains (CH1, CH2, and CH3). Similarly, from the N- to the C-terminus, each light chain has a variable region (VL), also known as the variable light chain domain or light chain variable domain, followed by a constant light chain (CL) domain. Depending on the amino acid sequence of its constant domain, the light chain of an antibody can be classified into one of two types, called κ and λ. A "naturally occurring sequence Fc region" includes an amino acid sequence that is the same as the amino acid sequence of an Fc region found in nature. A naturally occurring sequence human Fc region includes a naturally occurring sequence human IgG1 Fc region (non-A and A allotypes); a naturally occurring sequence human IgG2 Fc region; a naturally occurring sequence human IgG3 Fc region; and a naturally occurring sequence human IgG4 Fc region, as well as naturally occurring variants thereof. The term "package insert" is used to refer to the instructions that are typically included in the commercial packaging of a therapeutic product and that contain information about indications, usage, dosage, administration, combination therapies, contraindications, and / or warnings regarding the use of such therapeutic product. "Percent (%) amino acid sequence identity" relative to a reference polypeptide sequence is defined as the percentage of amino acid residues in the candidate sequence that are identical with the amino acid residues in the reference polypeptide sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways within the art, e.g., using publicly available computer software such as BLAST, BLAST-2, ALIGN, Megalign (DNASTAR) software or GENETYX® (Genetyx Co., Ltd.). One of ordinary skill in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. The ALIGN-2 sequence comparison computer program was written by Genentech, Inc., and the source code has been filed with the United States Copyright Office, Washington D.C., 20559, under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available from Genentech, Inc., South San Francisco, California, or can be compiled from the source code. The ALIGN-2 program should be compiled for use on UNIX operating systems, including Digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and are not varied. In the case of using ALIGN-2 for amino acid sequence comparison, the % amino acid sequence identity of a given amino acid sequence A over and / or relative to a given amino acid sequence B (or it can be expressed as a given amino acid sequence A that has or includes a particular % amino acid sequence identity over and / or relative to a given amino acid sequence B) is calculated as follows: 100 times the fraction X / Y, where X is the number of amino acid residues scored as identical matches by the sequence comparison program ALIGN-2 in the alignment of A and B by the program, and where Y is the total number of amino acid residues in B. It should be understood that when the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A over B will not be equal to the % amino acid sequence identity of B over A. Unless expressly stated otherwise, all % amino acid sequence identity values used herein are obtained using the ALIGN-2 computer program as described in the preceding paragraph. The term "pharmaceutical formulation" refers to a preparation that is in such a form as to permit the biological activity of the active ingredient contained therein to be effective, and that does not contain additional ingredients that are unacceptably toxic to the subject to which the formulation is to be administered. "Pharmaceutically acceptable carrier" refers to a component in a pharmaceutical formulation other than the active ingredient, which is non-toxic to the subject. Pharmaceutically acceptable carriers include, but are not limited to, buffers, excipients, stabilizers or preservatives. As used herein, the term "myostatin" can refer to any native myostatin from any vertebrate source, including mammals such as primates (e.g., humans) and rodents (e.g., mice and rats). Unless otherwise specified, the term "myostatin" refers to the human myostatin protein having the amino acid sequence shown in SEQ ID NO: 1 and comprising the C-terminal propeptide domain of human myostatin shown in SEQ ID NO: 75 or 78. This term encompasses "full-length", unprocessed myostatin and any form of myostatin produced by intracellular processing. This term also encompasses naturally occurring variants of myostatin, e.g., splice variants or allelic variants. The amino acid sequence of exemplary human myostatin is shown in SEQ ID NO: 1 (pro-myostatin). The amino acid sequence of the C-terminal growth factor domain of exemplary human myostatin is shown in SEQ ID NO: 2. The amino acid sequence of the N-terminal propeptide domain of exemplary human myostatin is shown in SEQ ID NO: 75 or 78. Active mature myostatin is a disulfide-linked homodimer composed of two C-terminal growth factor domains. Inactive latent myostatin is a non-covalent complex of two propeptides and mature myostatin. As disclosed herein, the antibodies of the present invention bind to inactive latent myostatin but not to the mature active myostatin homodimer. In some embodiments, the antibodies of the present invention bind to an epitope within the fragment consisting of amino acids 21-100 of the myostatin propeptide (SEQ ID NO: 78) but not to the mature active myostatin homodimer. The amino acid sequences of exemplary rhesus monkey and murine (murine) myostatin (pro-myostatin) are shown in SEQ ID NO: 3 and 5, respectively. The amino acid sequences of the C-terminal growth factor domains of exemplary rhesus monkey and murine myostatin are shown in SEQ ID NO: 4 and 6, respectively. The amino acid sequences of the N-terminal propeptide domains of exemplary rhesus monkey and murine myostatin are shown in SEQ ID NO: 76 or 79, and 77 or 80, respectively. GDF-11 (BMP-11) is a molecule closely related to myostatin, and they are both members of the TGF-β superfamily. Similar to myostatin, GDF11 is first synthesized as a precursor propeptide and then cleaved into an N-terminal prodomain and a C-terminal mature GDF11. The amino acid sequence of human GDF11 (precursor) is shown in SEQ ID NO: 81. The amino acid sequence of C-terminal mature human GDF11 is shown in SEQ ID NO: 82. The amino acid sequence of the N-terminal prodomain of human GDF11 is shown in SEQ ID NO: 83 or 84. The amino acid sequences of SEQ ID NO: 1, 3, 5, 78, 79, 80, 81, and 84 contain signal sequences corresponding to their amino acids 1-24, and the signal sequences are removed during processing in cells. As used herein, "treatment" (and grammatical variations thereof) refers to a clinical intervention that attempts to alter the natural course of an individual being treated and can be performed for prophylaxis or during the course of a clinical pathology. Desired therapeutic effects include, but are not limited to, preventing the occurrence or recurrence of a disease, alleviating symptoms, reducing any direct or indirect pathological consequences of the disease, preventing metastasis, reducing the rate of disease progression, improving or alleviating the disease state, and alleviating or improving the prognosis. In some embodiments, the antibodies of the invention are used to delay the development of a disease or slow the progression of a disease. The term "variable region" or "variable domain" refers to the domain of an antibody heavy or light chain that is involved in binding the antibody to an antigen. The variable domains of the heavy and light chains of a native antibody (VH and VL, respectively) generally have similar structures, each domain including four conserved framework regions (FRs) and three hypervariable regions (HVRs) (see, e.g., Kindt et al., Kuby Immunology, 6 th ed., W.H. Freeman and Co., page 91 (2007)). A single VH or VL domain may be sufficient to confer antigen-binding specificity. In addition, antibodies that bind to a particular antigen can be isolated using VH or VL domains from an antibody that binds that antigen to screen a complementary VL or VH domain library, respectively. See, e.g., Portolano et al., J. Immunol. 150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991). Due to at least one amino acid modification (modification), preferably one or more amino acid substitutions, a "variant Fc region" includes an amino acid sequence that is different from the native sequence Fc region. Preferably, the variant Fc region has at least one amino acid substitution, e.g., about 1 to 10 amino acid substitutions, preferably about 1 to 5 amino acid substitutions, in the native sequence Fc region or the Fc region of the parental polypeptide, compared to the native sequence Fc region or the Fc region of the parental polypeptide. The variant Fc regions herein will preferably have at least about 80% homology with the native sequence Fc region and / or the Fc region of the parental polypeptide, and most preferably have at least about 90% homology, more preferably have at least about 95% homology. The term "vector" as used herein refers to a nucleic acid molecule that is capable of replicating another nucleic acid to which it is linked. This term includes vectors as autonomous replicating nucleic acid structures, as well as vectors that are incorporated into the genome of a host cell into which they have been introduced. Certain vectors are capable of directing the expression of nucleic acids that are operably linked to them. Such vectors are referred to herein as "expression vectors". II. Compositions and Methods In one aspect, the invention is, in part, based on an anti - myostatin antibody and its use. In certain embodiments, an antibody that binds to myostatin is provided. The antibodies of the present invention are useful for, for example, the diagnosis and treatment of muscle atrophy diseases. In one aspect, the invention is, in part, based on a polypeptide comprising a variant Fc region and its use. In one embodiment, a polypeptide comprising a variant Fc region having enhanced FcγRIIb - binding activity is provided. In another embodiment, a polypeptide comprising a variant Fc region having an increased pI is provided. In some specific embodiments, the polypeptides of the present invention are antibodies. The polypeptides of the present invention comprising a variant Fc region are useful for, for example, the diagnosis and treatment of diseases. A. Exemplary anti - myostatin antibodies and polypeptides comprising variant Fc regions In one aspect, the present invention provides an isolated antibody that binds to myostatin. In some specific embodiments, the anti-myostatin antibody of the present invention binds to latent myostatin. In still other embodiments, the anti-myostatin antibody of the present invention binds to the myostatin propeptide (human: SEQ ID NO: 75 or 78; rhesus monkey: SEQ ID NO: 76 or 79; mouse: SEQ ID NO: 77 or 80). In still other embodiments, the antibody binds to an epitope within the fragment consisting of amino acids 21-100 of the myostatin propeptide (SEQ ID NO: 78). The propeptide is included as one of the components in latent myostatin, as described above. In some specific embodiments, the anti-myostatin antibody of the present invention inhibits the activation of myostatin. In some specific embodiments, the anti-myostatin antibody impedes the release of mature myostatin from latent myostatin. It has been reported that mature myostatin is released from latent myostatin by proteolytic and non-proteolytic steps. The anti-myostatin antibody of the present invention can impede the proteolytic and / or non-proteolytic release of mature myostatin from latent myostatin. In some specific embodiments, the anti-myostatin antibody impedes the proteolytic cleavage of latent myostatin. In some specific embodiments, the anti-myostatin antibody impedes the access of proteases to latent myostatin (especially to the proteolytic cleavage site (Arg98-Asp99) of latent myostatin). In still other embodiments, the protease can be a metalloprotease of the BMP1 / TLD family, such as BMP1, TED, tolloid-like protein-1 (TLL-1) or tolloid-like protein-2 (TLL-2). In another embodiment, the anti-myostatin antibody impedes the non-proteolytic release of mature myostatin from latent myostatin. The non-proteolytic release used herein represents the spontaneous release of mature myostatin from latent myostatin, which is not accompanied by the proteolytic cleavage of latent myostatin. The non-proteolytic release includes, for example, the release of mature myostatin by culturing latent myostatin, such as under conditions of 37°C in the absence of proteases that cleave latent myostatin. In some specific embodiments, the anti-myostatin antibody of the present invention does not bind to mature myostatin. In some embodiments, the anti-myostatin antibody binds to the same epitope as the antibody described in Table 2a. In some embodiments, the anti-myostatin antibody competes with the antibody described in Table 2a for binding to latent myostatin. In some additional embodiments, the anti-myostatin antibody competes with the antibody comprising the VH and VL pair described in Table 2a for binding to latent myostatin. In some embodiments, the anti-myostatin antibody competes with the antibody described in Table 2a for binding to the fragment consisting of amino acids 21-100 of the myostatin propeptide (SEQ ID NO: 78). In still other embodiments, the anti-myostatin antibody binds to the same epitope as the antibody described in Table 11a or 13. In some embodiments, the anti-myostatin antibody competes with the antibody described in Table 11a or 13 for binding to latent myostatin.In some embodiments, the anti - myostatin antibody competes for binding with the antibody described in Table 11a or 13 to a fragment consisting of amino acids 21 - 100 of the myostatin native peptide (SEQ ID NO: 78). In some embodiments, the anti - myostatin antibody of the invention binds to latent myostatin and inhibits the activation of myostatin. In still other embodiments, the antibody: (a) impedes the release of mature myostatin from latent myostatin; (b) impedes the proteolytic release of mature myostatin; (c) impedes the spontaneous release of mature myostatin; or (d) does not bind to mature myostatin; or binds to an epitope within the fragment consisting of amino acids 21 - 100 of the myostatin native peptide (SEQ ID NO: 78). In still other embodiments, the antibody competes for binding to latent myostatin with an antibody comprising the VH and VL pairs described in Table 2a, 11a or 13, or binds to the same epitope as an antibody comprising the VH and VL pairs described in Table 2a, 11a or 13. In still other embodiments, the antibody binds to latent myostatin with a higher affinity at neutral pH (e.g., pH 7.4) than at acidic pH (e.g., pH 5.8). In still other embodiments, the antibody is (a) a monoclonal antibody; (b) a human, humanized or chimeric antibody; (c) a full - length IgG antibody; or (d) an antibody fragment that binds to latent myostatin or the myostatin native peptide. In another embodiment, the myostatin antibody of the present invention is not bound to GDF11. In some specific embodiments, the myostatin antibody of the present invention does not inhibit the activation of GDF11. In some specific embodiments, the myostatin antibody does not impede the release of mature GDF11 from latent GDF11. The myostatin antibody of the present invention does not impede the proteolytic and non-proteolytic release of mature GDF11 from latent GDF11. In some specific embodiments, the myostatin antibody does not impede the proteolytic cleavage of latent GDF11. In some specific embodiments, the myostatin antibody does not impede the access of proteases to latent GDF11 (particularly to the proteolytic cleavage site of latent GDF11). In still other embodiments, the protease can be a metalloprotease of the BMP1 / TLD family, such as BMP1, TED, tolloid-like protein 1 (TLL-1) or tolloid-like protein 2 (TLL-2). Non-proteolytic release as used herein represents the spontaneous release of mature GDF11 from latent GDF11, which is not accompanied by the proteolytic cleavage of latent GDF11. Non-proteolytic release includes, for example, the release of mature GDF11 by culturing latent GDF11, such as under conditions where there is no protease that cleaves latent GDF11 at 37°C. Most of the currently known myostatin antibodies are not specific for myostatin. These antibodies have high affinity for other members of the TGF-β superfamily (such as GDF11) and neutralize their biological activities. GDF11 plays an important role during embryogenesis and is responsible for the homeotic transformation of the axial skeleton. Homozygous GDF11 knockout mice are perinatal lethal, and mice with a wild-type GDF11 gene duplication can survive but have skeletal defects. Since GDF11 plays an important role during embryogenesis, inhibitors that inhibit GDF11 pose a theoretical safety risk, which may cause toxicity in treated patients or reproductive toxicity in, for example, women of childbearing age. Therefore, specific inhibition of myostatin activity is needed in the treatment of myostatin-related disorders, where the treatment is desired to increase muscle mass, size, strength, etc., and is particularly needed in women of childbearing age. In another aspect, the invention provides an anti - myostatin antibody that exhibits pH - dependent binding characteristics. As used herein, the term "pH - dependent" means that the antibody shows "reduced binding to myostatin at acidic pH compared to neutral pH" (for the purposes of this disclosure, the two terms are used interchangeably). For example, an antibody "having pH - dependent binding characteristics" includes an antibody that binds to myostatin with a higher affinity at neutral pH compared to acidic pH. In certain embodiments, the antibody of the present invention binds to myostatin with an affinity that is at least 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000, or more times higher at neutral pH compared to acidic pH. In some embodiments, the antibody binds to myostatin (e.g., latent myostatin or propeptide myostatin) with a higher affinity at pH 7.4 than at pH 5.8. In still other embodiments, the antibody of the present invention binds to myostatin with an affinity that is at least 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000, or more times higher at pH 7.4 than at pH 5.8. When the antigen is a soluble protein, the binding of the antibody to the antigen can result in an extension of the antigen's half - life in plasma (i.e., reduced clearance of the antigen from plasma), because the antibody can have a longer half - life in plasma than the antigen itself and can act as a carrier for the antigen. This is due to the recycling of the antigen - antibody complex through the endosomal pathway in cells by FcRn (Roopenian, Nat. Rev. Immunol.7(9): 715 - 725 (2007)). However, an antibody with pH - dependent binding characteristics, which binds to its antigen in the neutral extracellular environment and releases the antigen into the acidic endosomal compartment as it enters the cell, is expected to have superior performance in antigen neutralization and clearance in relation to its pH - dependent mode of binding (Igawa et al., Nature Biotechnol. 28(11):1203 - 1207 (2010); Devanaboyina et al., mAbs5(6):851 - 859 (2013); WO 2009 / 125825). The "affinity" of an antibody for myostatin, for the purposes of this disclosure, is expressed in terms of the KD of the antibody. The KD of an antibody is the equilibrium dissociation constant of the antibody-antigen interaction. The larger the KD value of an antigen binding to its antigen, the weaker its binding affinity for that particular antigen. Thus, as used herein, "higher affinity at neutral pH compared to acidic pH" (or equivalent expression "pH-dependent binding") means that the KD of the antibody binding to myostatin at acidic pH is greater than the KD of the antibody binding to myostatin at neutral pH. For example, in the context of the present invention, if the KD of the antibody binding to myostatin at acidic pH is at least greater than twice the KD of the antibody binding to myostatin at neutral pH, the antibody is considered to bind to myostatin with higher affinity at neutral pH than at acidic pH. Accordingly, the present invention encompasses antibodies having a KD for binding to myostatin at acidic pH that is at least 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000 or more times greater than the KD of the antibody binding to myostatin at neutral pH. In another embodiment, the KD value of the antibody at neutral pH can be 10 -7 M, 10 -8 M, 10 -9 M, 10 -10 M, 10 -11 M, 10 -12 M or less. In another embodiment, the KD value of the antibody at acidic pH can be 10 -9 M, 10 -8 M, 10 -7 M, 10 -6 M or greater. In some other embodiments, an antibody is considered to bind to myostatin (e.g., latent myostatin or propeptide myostatin) with higher affinity at neutral pH compared to acidic pH if the KD of the antibody binding to myostatin at pH 5.8 is at least greater than twice the KD of the antibody binding to myostatin at pH 7.4. In some embodiments, the provided antibody has a KD for binding to myostatin at pH 5.8 that is at least 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000 or more times greater than the KD of the antibody binding to myostatin at pH 7.4. In another embodiment, the KD value of the antibody at pH 7.4 can be 10 -7 M, 10 -8 M, 10 -9 M, 10 -10 M, 10 -11 M, 10 -12 M or less. In another embodiment, the KD value of the antibody at pH 5.8 can be 10 -9 M, 10 -8 M, 10 -7 M, 10 -6 M or greater. The binding characteristics of an antibody to a specific antigen can also be represented by the kd of the antibody. The kd of an antibody refers to the dissociation rate constant of the antibody for a specific antigen, expressed as the reciprocal of seconds (i.e., sec -1 ). An increase in the kd value indicates weaker binding of the antibody to its antigen. The present invention thus encompasses antibodies that bind to myostatin with a higher kd value at acidic pH compared to neutral pH. The present invention encompasses antibodies having a kd for binding to myostatin at acidic pH that is at least 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000 or more times greater than the kd of the antibody binding to myostatin at neutral pH. In another embodiment, the kd value of the antibody at neutral pH can be 10 -2 1 / s, 10 -3 1 / s, 10 -4 1 / s, 10 -5 1 / s, 10 -6 1 / s or less. In another embodiment, the kd value of the antibody can be 10 at acidic pH -3 1 / s, 10 -2 1 / s, 10 -1 1 / s or greater. The present invention also includes antibodies that bind to myostatin (e.g., latent myostatin or propeptide myostatin) with a larger kd value at pH 5.8 compared to at pH 7.4. The present invention includes antibodies in which the kd for binding to myostatin at pH 5.8 is at least 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000 or more times greater than the kd for binding to myostatin at pH 7.4. In another embodiment, the kd value of the antibody at pH 7.4 can be 10 -2 1 / s, 10 -3 1 / s, 10 -4 1 / s, 10 -5 1 / s, 10 -6 1 / s or less. In another embodiment, the kd value of the antibody at pH 5.8 can be 10 -3 1 / s, 10 -2 1 / s, 10 -1 1 / s or greater. In certain instances, "binding of myostatin is reduced at acidic pH compared to neutral pH" is expressed as the ratio of the KD value of antibody binding to myostatin at acidic pH to the KD value of antibody binding to myostatin at neutral pH (or vice versa). For example, for the purposes of the present invention, if an antibody has an acidic / neutral KD ratio of 2 or greater, the antibody can be considered "binding of myostatin is reduced at acidic pH compared to neutral pH". In some particular embodiments, the pH 5.8 / pH 7.4 KD ratio of the anti-myostatin antibody of the present invention can be 2 or greater. In some particular exemplary embodiments, the acidic / neutral KD ratio of the antibody of the present invention can be 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000 or greater. In another embodiment, the KD value of the antibody at neutral pH can be 10 -7 M, 10 -8 M, 10 -9 M, 10 -10 M, 10 -11 M, 10 -12 M or less. In another embodiment, the KD value of the antibody at acidic pH can be 10 -9 M, 10 -8 M, 10 -7 M, 10 -6 M or greater. In a further example, if the pH 5.8 / pH 7.4 KD ratio of the antibody is 2 or greater, the antibody can be considered "binding of myostatin (e.g., latent myostatin) is reduced at acidic pH compared to neutral pH". In some particular exemplary embodiments, the pH 5.8 / pH 7.4 KD ratio of the antibody can be 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000 or greater. In another embodiment, the KD value of the antibody at pH 7.4 can be 10 -7 M, 10 -8 M, 10 -9 M, 10 -10 M, 10 -11 M, 10 -12 M or less. In another embodiment, the KD value of the antibody at pH 5.8 can be 10 -9 M, 10 -8 M, 10 -7 M, 10 -6 M or greater. In certain instances, "binding to myostatin is reduced at acidic pH compared to neutral pH" is expressed as the ratio of the kd value of the antibody binding to myostatin at acidic pH to the kd value of the antibody binding to myostatin at neutral pH (or vice versa). For example, for the purposes of the present invention, if the antibody has an acidic / neutral kd ratio of 2 or greater, then the antibody can be considered "binding to myostatin is reduced at acidic pH compared to neutral pH". In some specific exemplary embodiments, the pH 5.8 / pH 7.4 kd ratio of the antibody of the present invention can be 2 or greater. In some specific exemplary embodiments, the acidic / neutral kd ratio of the antibody of the present invention can be 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000 or greater. In another embodiment, the kd value of the antibody at neutral pH can be 10 -2 1 / s, 10 -3 1 / s, 10 -4 1 / s, 10 -5 1 / s, 10 -6 1 / s or less. In another embodiment, the kd value of the antibody at acidic pH can be 10 -3 1 / s, 10 -2 1 / s, 10 -11 / s or greater. In some specific exemplary embodiments, the pH5.8 / pH7.4 kd ratio of the antibody can be 2, 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 400, 1000, 10000 or greater. In another embodiment, the kd value of the antibody at pH7.4 can be 10 -2 1 / s, 10 -3 1 / s, 10 -4 1 / s, 10 -5 1 / s, 10 -6 1 / s or less. In another embodiment, the kd value of the antibody at pH5.8 can be 10 -3 1 / s, 10 -2 1 / s, 10 -1 1 / s or greater. As used herein, the term "acidic pH" refers to a pH of 4.0 to 6.5. The term "acidic pH" includes any pH value among 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, and 6.5. In a particular aspect, the "acidic pH" is 5.8. As used herein, the term "neutral pH" refers to a pH of 6.7 to about 10.0. The term "neutral pH" includes any pH value among 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, and 10.0. In a particular aspect, the "neutral pH" is 7.4. The KD value and kd value, as represented herein, can be measured using a surface plasmon resonance-based biosensor to characterize the antibody-antigen interaction (see, for example, Example 7 in the text). The KD value and kd value can be measured at 25°C or 37°C. In some specific embodiments, the myostatin antibody of the present invention binds to myostatins from more than one species. In still other embodiments, the myostatin antibody binds to myostatins from human and non-human species. In still other embodiments, the myostatin antibody binds to myostatins from human, mouse, and monkey (rhesus monkey, cynomolgus monkey, marmoset, chimpanzee, or baboon). In some specific embodiments, the myostatin antibody of the present invention binds to latent myostatins from more than one species. In still other embodiments, the myostatin antibody binds to latent myostatins from human and non-human species. In still other embodiments, the myostatin antibody binds to latent myostatins from human, mouse, and monkey. In some specific embodiments, the myostatin antibody of the present invention binds to propeptide myostatins from more than one species. In still other embodiments, the myostatin antibody binds to propeptide myostatins from human and non-human species. In still other embodiments, the myostatin antibody binds to propeptide myostatins from human, mouse, and monkey. In yet another aspect, the invention provides a myostatin antibody that forms an immune complex with myostatin (i.e., an antigen-antibody complex). In some specific embodiments, two or more myostatin antibodies bind to two or more myostatin molecules to form an immune complex. This is possible because myostatin exists as a homodimer containing two myostatin molecules, and an antibody has two antigen-binding sites. The myostatin antibody can bind to the same antigenic determinant on the myostatin molecule or can bind to different antigenic determinants on the myostatin molecule, much like a bispecific antibody. Generally, when two or more antibodies form an immune complex with two or more antigens, the resulting immune complex can strongly bind to Fc receptors present on the cell surface because of the avidity effect through the Fc region of the antibodies in the complex and can then be efficiently internalized into the cell. Thus, the myostatin antibody capable of forming an immune complex containing two or more myostatin antibodies and two or more myostatin molecules can result in the rapid clearance of myostatin from plasma in vivo through strong binding to Fc receptors due to the avidity effect. In addition, antibodies with pH-dependent binding characteristics are considered to have superior performance in antigen neutralization and clearance, which relates to their pH-dependent binding mode (Igawa et al., Nature Biotech. 28(11):1203 - 1207 (2010); Devanaboyina et al., mAbs5(6):851-859 (2013); WO 2009 / 125825). Thus, antibodies having the above two properties, namely, antibodies having pH-dependent binding characteristics and forming immune complexes comprising two or more antibodies and two or more antigens, are expected to have even superior properties to highly accelerate the elimination of antigens from plasma (WO 2013 / 081143). In another aspect, the invention provides an anti-myostatin antibody comprising at least one, two, three, four, five or six hypervariable regions (HVRs) selected from (a) HVR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 55-57, 114-115, 126; (b) HVR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 58-60, 116-120, 127; (c) HVR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 61-64, 121, 128; (d) HVR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 65-69, 122-124, 129; (e) HVR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 70-72, 125, 130; and (f) HVR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 73-74, 131. In another aspect, the invention provides an anti-myostatin antibody comprising at least one, two, three, four, five or six HVRs selected from (a) HVR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 55-57; (b) HVR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 58-60; (c) HVR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 61-64; (d) HVR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 65-69; (e) HVR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 70-72; and (f) HVR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 73-74. In another aspect, the invention provides an anti - myostatin antibody that comprises at least one, two, three, four, five, or six hypervariable regions (HVRs) selected from: (a) HVR - H1 comprising the amino acid sequence of any one of SEQ ID NOs: 114 - 115; (b) HVR - H2 comprising the amino acid sequence of any one of SEQ ID NOs: 116 - 120; (c) HVR - H3 comprising the amino acid sequence of SEQ ID NO: 121; (d) HVR - L1 comprising the amino acid sequence of any one of SEQ ID NOs: 122 - 124; (e) HVR - L2 comprising the amino acid sequence of SEQ ID NO: 125; and (f) HVR - L3 comprising the amino acid sequence of any one of SEQ ID NOs: 73 - 74. In another aspect, the invention provides an anti - myostatin antibody that comprises at least one, two, three, four, five, or six HVRs selected from: (a) HVR - H1 comprising the amino acid sequence of SEQ ID NO: 114; (b) HVR - H2 comprising the amino acid sequence of SEQ ID NO: 58; (c) HVR - H3 comprising the amino acid sequence of SEQ ID NO: 63; (d) HVR - L1 comprising the amino acid sequence of SEQ ID NO: 122; (e) HVR - L2 comprising the amino acid sequence of SEQ ID NO: 71; and (f) HVR - L3 comprising the amino acid sequence of SEQ ID NO: 74. In another aspect, the invention provides an anti - myostatin antibody that comprises at least one, two, three, four, five, or six HVRs selected from: (a) HVR - H1 comprising the amino acid sequence of SEQ ID NO: 114; (b) HVR - H2 comprising the amino acid sequence of SEQ ID NO: 58; (c) HVR - H3 comprising the amino acid sequence of SEQ ID NO: 63; (d) HVR - L1 comprising the amino acid sequence of SEQ ID NO: 123; (e) HVR - L2 comprising the amino acid sequence of SEQ ID NO: 71; and (f) HVR - L3 comprising the amino acid sequence of SEQ ID NO: 74. In one aspect, the invention provides an anti - myostatin antibody that comprises at least one, two, three, four, five, or six HVRs selected from: (a) HVR - H1 comprising the amino acid sequence of SEQ ID NO: 126; (b) HVR - H2 comprising the amino acid sequence of SEQ ID NO: 127; (c) HVR - H3 comprising the amino acid sequence of SEQ ID NO: 128; (d) HVR - L1 comprising the amino acid sequence of SEQ ID NO: 129; (e) HVR - L2 comprising the amino acid sequence of SEQ ID NO: 130; and (f) HVR - L3 comprising the amino acid sequence of SEQ ID NO: 131. In one aspect, the invention provides an antibody comprising at least one, at least two, or all three VH HVR sequences selected from (a) HVR-H1 comprising any of the amino acid sequences set forth in SEQ ID NOs: 55-57, 114-115, 126; (b) HVR-H2 comprising any of the amino acid sequences set forth in SEQ ID NOs: 58-60, 116-120, 127; and (c) HVR-H3 comprising any of the amino acid sequences set forth in SEQ ID NOs: 61-64, 121, 128. In one embodiment, the antibody comprises HVR-H3, which comprises any of the amino acid sequences set forth in SEQ ID NOs: 61-64, 121, 128. In another embodiment, the antibody comprises: HVR-H3, which comprises any of the amino acid sequences set forth in SEQ ID NOs: 61-64, 121, 128, and HVR-L3, which comprises any of the amino acid sequences set forth in SEQ ID NOs: 73-74, 131. In yet another embodiment, the antibody comprises: HVR-H3, which comprises any of the amino acid sequences set forth in SEQ ID NOs: 61-64, 121, 128, HVR-L3, which comprises any of the amino acid sequences set forth in SEQ ID NOs: 73-74, 131, and HVR-H2, which comprises any of the amino acid sequences set forth in SEQ ID NOs: 58-60, 116-120, 127. In yet another embodiment, the antibody comprises (a) HVR-H1 comprising any of the amino acid sequences set forth in SEQ ID NOs: 55-57, 114-115, 126; (b) HVR-H2 comprising any of the amino acid sequences set forth in SEQ ID NOs: 58-60, 116-120, 127; and (c) HVR-H3 comprising any of the amino acid sequences set forth in SEQ ID NOs: 61-64, 121, 128. In one aspect, the invention provides an antibody comprising at least one, at least two, or all three VH HVR sequences selected from (a) HVR-H1 comprising an amino acid sequence of any one of SEQ ID NOs: 55-57; (b) HVR-H2 comprising an amino acid sequence of any one of SEQ ID NOs: 58-60; and (c) HVR-H3 comprising an amino acid sequence of any one of SEQ ID NOs: 61-64. In one embodiment, the antibody comprises HVR-H3 comprising an amino acid sequence of any one of SEQ ID NOs: 61-64. In another embodiment, the antibody comprises: HVR-H3 comprising an amino acid sequence of any one of SEQ ID NOs: 61-64, and HVR-L3 comprising an amino acid sequence of any one of SEQ ID NOs: 73-74. In yet another embodiment, the antibody comprises: HVR-H3 comprising an amino acid sequence of any one of SEQ ID NOs: 61-64, HVR-L3 comprising an amino acid sequence of any one of SEQ ID NOs: 73-74, and HVR-H2 comprising an amino acid sequence of any one of SEQ ID NOs: 58-60. In yet another embodiment, the antibody comprises (a) HVR-H1 comprising an amino acid sequence of any one of SEQ ID NOs: 55-57; (b) HVR-H2 comprising an amino acid sequence of any one of SEQ ID NOs: 58-60; and (c) HVR-H3 comprising an amino acid sequence of any one of SEQ ID NOs: 61-64. In one aspect, the invention provides an antibody comprising at least one, at least two, or all three VH HVR sequences selected from (a) HVR-H1 comprising an amino acid sequence selected from SEQ ID NOs: 114-115; (b) HVR-H2 comprising an amino acid sequence selected from SEQ ID NOs: 116-120; and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 121. In one embodiment, the antibody comprises HVR-H3, which comprises the amino acid sequence of SEQ ID NO: 121. In another embodiment, the antibody comprises: HVR-H3, which comprises the amino acid sequence of SEQ ID NO: 121, and HVR-L3, which comprises an amino acid sequence selected from SEQ ID NOs: 73-74. In yet another embodiment, the antibody comprises: HVR-H3, which comprises the amino acid sequence of SEQ ID NO: 121, HVR-L3, which comprises an amino acid sequence selected from SEQ ID NOs: 73-74, and HVR-H2, which comprises an amino acid sequence selected from SEQ ID NOs: 116-120. In yet another embodiment, the antibody comprises (a) HVR-H1 comprising an amino acid sequence selected from SEQ ID NOs: 114-115; (b) HVR-H2 comprising an amino acid sequence selected from SEQ ID NOs: 116-120; and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 121. In another aspect, the invention provides an antibody comprising at least one, at least two, or all three VH HVR sequences selected from (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 114; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 58; and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 63. In one embodiment, the antibody comprises HVR-H3, which comprises the amino acid sequence of SEQ ID NO: 63. In another embodiment, the antibody comprises: HVR-H3, which comprises the amino acid sequence of SEQ ID NO: 63, and HVR-L3, which comprises the amino acid sequence of SEQ ID NO: 74. In yet another embodiment, the antibody comprises: HVR-H3, which comprises the amino acid sequence of SEQ ID NO: 63, HVR-L3, which comprises the amino acid sequence of SEQ ID NO: 74, and HVR-H2, which comprises the amino acid sequence of SEQ ID NO: 58. In yet another embodiment, the antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 114; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 58; and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 63. In another aspect, the invention provides an antibody comprising at least one, at least two, or all three VH HVR sequences selected from (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 126; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 127; and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 128. In one embodiment, the antibody comprises HVR-H3, which comprises the amino acid sequence of SEQ ID NO: 128. In another embodiment, the antibody comprises: HVR-H3, which comprises the amino acid sequence of SEQ ID NO: 128, and HVR-L3, which comprises the amino acid sequence of SEQ ID NO: 131. In yet another embodiment, the antibody comprises: HVR-H3, which comprises the amino acid sequence of SEQ ID NO: 128, HVR-L3, which comprises the amino acid sequence of SEQ ID NO: 131, and HVR-H2, which comprises the amino acid sequence of SEQ ID NO: 127. In yet another embodiment, the antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 126; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 127; and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 128. In another aspect, the invention provides an antibody comprising at least one, at least two, or all three VL HVR sequences selected from (a) HVR-L1 comprising any one of the amino acid sequences of SEQ ID NOs: 65-69, 122-124, 129; (b) HVR-L2 comprising any one of the amino acid sequences of SEQ ID NOs: 70-72, 125, 130; and (c) HVR-L3 comprising any one of the amino acid sequences of SEQ ID NOs: 73-74, 131. In one embodiment, the antibody comprises (a) HVR-L1 comprising any one of the amino acid sequences of SEQ ID NOs: 65-69, 122-124, 129; (b) HVR-L2 comprising any one of the amino acid sequences of SEQ ID NOs: 70-72, 125, 130; and (c) HVR-L3 comprising any one of the amino acid sequences of SEQ ID NOs: 73-74, 131. In another aspect, the present invention provides an antibody comprising at least one, at least two, or all three VL HVR sequences selected from (a) HVR-L1 comprising an amino acid sequence of any one of SEQ ID NOs: 65-69; (b) HVR-L2 comprising an amino acid sequence of any one of SEQ ID NOs: 70-72; and (c) HVR-L3 comprising an amino acid sequence of any one of SEQ ID NOs: 73-74. In one embodiment, the antibody comprises (a) HVR-L1 comprising an amino acid sequence of any one of SEQ ID NOs: 65-69; (b) HVR-L2 comprising an amino acid sequence of any one of SEQ ID NOs: 70-72; and (c) HVR-L3 comprising an amino acid sequence of any one of SEQ ID NOs: 73-74. In another aspect, the present invention provides an antibody comprising at least one, at least two, or all three VL HVR sequences selected from (a) HVR-L1 comprising an amino acid sequence of any one of SEQ ID NOs: 122-124; (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 125; and (c) HVR-L3 comprising an amino acid sequence of any one of SEQ ID NOs: 73-74. In one embodiment, the antibody comprises (a) HVR-L1 comprising an amino acid sequence of any one of SEQ ID NOs: 122-124; (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 125; and (c) HVR-L3 comprising an amino acid sequence of any one of SEQ ID NOs: 73-74. In another aspect, the present invention provides an antibody comprising at least one, at least two, or all three VL HVR sequences selected from (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 122; (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 71; and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 74. In one embodiment, the antibody comprises (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 122; (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 71; and (c) HVR-L3 comprising an amino acid sequence of any one of SEQ ID NOs: 74. In another aspect, the present invention provides an antibody comprising at least one, at least two, or all three VL HVR sequences selected from (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 123; (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 71; and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 74. In one embodiment, the antibody comprises (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 123; (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 71; and (c) HVR-L3 comprising an amino acid sequence of any one of SEQ ID NOs: 74. In another aspect, the invention provides an antibody that comprises at least one, at least two, or all three VL HVR sequences selected from (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 129; (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 130; and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 131. In one embodiment, the antibody comprises (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 129; (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 130; and (c) HVR-L3 comprising the amino acid sequence of any one of SEQ ID NO: 131. In another aspect, the antibody of the invention comprises (a) a VH domain that comprises at least one, at least two, or all three VH HVR sequences selected from (i) HVR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 55-57, 114, 115, 126, (ii) HVR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 58-60, 116-120, 127, and (iii) HVR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 61-64, 121, 128; and (b) a VL domain that comprises at least one, at least two, or all three VL HVR sequences selected from (i) HVR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 65-69, 122-124, 129, (ii) HVR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 70-72, 125, 130, and (iii) HVR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 73-74, 131. In another aspect, the antibody of the invention comprises (a) a VH domain that comprises at least one, at least two, or all three VH HVR sequences selected from (i) HVR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 55-57, (ii) HVR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 58-60, and (iii) HVR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 61-64; and (b) a VL domain that comprises at least one, at least two, or all three VL HVR sequences selected from (i) HVR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 65-69, (ii) HVR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 70-72, and (iii) HVR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 73-74. In another aspect, the antibody of the invention comprises (a) a VH domain comprising at least one, at least two, or all three VH HVR sequences selected from (i) HVR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 114-115, (ii) HVR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 116-120, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 121; and (b) a VL domain comprising at least one, at least two, or all three VL HVR sequences selected from (i) HVR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 122-124, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 125, and (iii) HVR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 73-74. In another aspect, the antibody of the invention comprises (a) a VH domain comprising at least one, at least two, or all three VH HVR sequences selected from (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 114, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 63; and (b) a VL domain comprising at least one, at least two, or all three VL HVR sequences selected from (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 122, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 71, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 74. In another aspect, the antibody of the invention comprises (a) a VH domain comprising at least one, at least two, or all three VH HVR sequences selected from (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 114, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 63; and (b) a VL domain comprising at least one, at least two, or all three VL HVR sequences selected from (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 123, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 71, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 74. In another aspect, the antibody of the invention comprises (a) a VH domain comprising at least one, at least two, or all three VH HVR sequences selected from (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 126, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 127, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 128; and (b) a VL domain comprising at least one, at least two, or all three VL HVR sequences selected from (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 129, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 130, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 131. In another aspect, the invention provides an antibody comprising: (a) HVR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 55-57, 114-115, 126; (b) HVR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 58-60, 116-120, 127; (c) HVR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 61-64, 121, 128; (d) HVR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 65-69, 122-124, 129; (e) HVR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 70-72, 125, 130; and (f) HVR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 73-74, 131. In another aspect, the invention provides an antibody comprising: (a) HVR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 55-57, 114-115; (b) HVR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 58-60, 116-120; (c) HVR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 61-64, 121; (d) HVR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 65-69, 122-124; (e) HVR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 70-72, 125; and (f) HVR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 73-74. In another aspect, the invention provides an antibody comprising: (a) an HVR-H1 comprising an amino acid sequence of any one of SEQ ID NOs: 114-115; (b) an HVR-H2 comprising an amino acid sequence of any one of SEQ ID NOs: 116-120; (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 121; (d) an HVR-L1 comprising an amino acid sequence of any one of SEQ ID NOs: 122-124; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 125; and (f) an HVR-L3 comprising an amino acid sequence of any one of SEQ ID NOs: 73-74. In another aspect, the invention provides an antibody comprising: (a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 114; (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 58; (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 63; (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 122; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 71; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 74. In another aspect, the invention provides an antibody comprising: (a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 114; (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 58; (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 63; (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 123; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 71; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 74. In another aspect, the invention provides an antibody comprising: (a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 126; (b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 127; (c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 128; (d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 129; (e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 130; and (f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 131. In some specific embodiments, any one or more amino acids of the myostatin antibody provided above are substituted at the following HVR positions: (a) in HVR-H1 (SEQ ID NO: 55), at positions 1 and 2; (b) in HVR-H2 (SEQ ID NO: 58), at positions 4, 7, 8, 10, 11, 12, and 16; (c) in HVR-H3 (SEQ ID NO: 61), at positions 5, 7, and 11; (d) in HVR-L1 (SEQ ID NO: 65), at positions 1, 2, 5, 7, 8, and 9; (e) in HVR-L2 (SEQ ID NO: 70), at positions 3 and 7; and (f) in HVR-L3 (SEQ ID NO: 73), at position 8. In some specific embodiments, one or more amino acid substitutions of the myostatin antibody are conservative substitutions, as provided herein. In some specific embodiments, any one or more of the following substitutions can be made in any combination: (a) in HVR-H1 (SEQ ID NO: 55), S1H; Y2T, D, or E; (b) in HVR-H2 (SEQ ID NO: 58), Y4H; S7K; T8M or K; Y10K; A11M or E; S12E; G16K; (c) in HVR-H3 (SEQ ID NO: 61), Y5H; T7H; L11K; (d) in HVR-L1 (SEQ ID NO: 65), Q1T, S2T; S5E; Y7F; D8H; N9D, A, or E; (e) in HVR-L2 (SEQ ID NO: 70), S3E; S7Y, F, or W; and (f) in HVR-L3 (SEQ ID NO: 73), L8R. All possible combinations of the above substitutions are covered by SEQ ID NOs: 126, 127, 128, 129, 130, and 131, which are the consensus sequences of HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3, respectively. In any of the above embodiments, the myostatin antibody can be humanized. In one embodiment, the myostatin antibody comprises an HVR as in any of the above embodiments, and further comprises a receptor human framework, for example, a human immunoglobulin framework or a human consensus framework. In another embodiment, the myostatin antibody comprises an HVR as in any of the above embodiments, and further comprises a VH or VL, which comprises an FR sequence. In yet another embodiment, the myostatin antibody comprises the following heavy chain and / or light chain variable domain FR sequences. For the heavy chain variable domain, FR1 comprises the amino acid sequence of any one of SEQ ID NOs: 132-134, FR2 comprises the amino acid sequence of any one of SEQ ID NOs: 135-136, FR3 comprises the amino acid sequence of SEQ ID NO: 137, and FR4 comprises the amino acid sequence of SEQ ID NO: 138. For the light chain variable domain, FR1 comprises the amino acid sequence of SEQ ID NO: 139, FR2 comprises the amino acid sequence of any one of SEQ ID NOs: 140-141, FR3 comprises the amino acid sequence of any one of SEQ ID NOs: 142-143, and FR4 comprises the amino acid sequence of SEQ ID NO: 144. In one aspect, the invention provides a myostatin antibody that comprises at least one, two, three, four, five, or six HVRs selected from: (a) HVR-H1 comprising the amino acid sequence of any one of SEQ ID NOs: 157-162; (b) HVR-H2 comprising the amino acid sequence of any one of SEQ ID NOs: 163-168; (c) HVR-H3 comprising the amino acid sequence of any one of SEQ ID NOs: 169-174; (d) HVR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 175-180; (e) HVR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 181-186; and (f) HVR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 187-192. In one aspect, the invention provides an antibody comprising at least one, at least two, or all three VH HVR sequences selected from (a) HVR-H1 comprising any one of the amino acid sequences set forth in SEQ ID NOs: 157-162; (b) HVR-H2 comprising any one of the amino acid sequences set forth in SEQ ID NOs: 163-168; and (c) HVR-H3 comprising any one of the amino acid sequences set forth in SEQ ID NOs: 169-174. In one embodiment, the antibody comprises HVR-H3, which comprises any one of the amino acid sequences set forth in SEQ ID NOs: 169-174. In another embodiment, the antibody comprises: HVR-H3, which comprises any one of the amino acid sequences set forth in SEQ ID NOs: 169-174, and HVR-L3, which comprises any one of the amino acid sequences set forth in SEQ ID NOs: 187-192. In yet another embodiment, the antibody comprises: HVR-H3, which comprises any one of the amino acid sequences set forth in SEQ ID NOs: 169-174, HVR-L3, which comprises any one of the amino acid sequences set forth in SEQ ID NOs: 187-192, and HVR-H2, which comprises any one of the amino acid sequences set forth in SEQ ID NOs: 163-168. In yet another embodiment, the antibody comprises (a) HVR-H1 comprising any one of the amino acid sequences set forth in SEQ ID NOs: 157-162; (b) HVR-H2 comprising any one of the amino acid sequences set forth in SEQ ID NOs: 163-168; and (c) HVR-H3 comprising any one of the amino acid sequences set forth in SEQ ID NOs: 169-174. In another aspect, the antibody of the invention comprises at least one, at least two, or all three VL HVR sequences selected from (a) HVR-L1 comprising any one of the amino acid sequences set forth in SEQ ID NOs: 175-180; (b) HVR-L2 comprising any one of the amino acid sequences set forth in SEQ ID NOs: 181-186; and (c) HVR-L3 comprising any one of the amino acid sequences set forth in SEQ ID NOs: 187-192. In one embodiment, the antibody comprises (a) HVR-L1 comprising any one of the amino acid sequences set forth in SEQ ID NOs: 175-180; (b) HVR-L2 comprising any one of the amino acid sequences set forth in SEQ ID NOs: 181-186; and (c) HVR-L3 comprising any one of the amino acid sequences set forth in SEQ ID NOs: 187-192 of the VL HVR sequence. In another aspect, the antibody of the invention comprises (a) a VH domain comprising at least one, at least two, or all three VH HVR sequences selected from (i) HVR-H1 comprising an amino acid sequence of any one of SEQ ID NOs: 157-162, (ii) HVR-H2 comprising an amino acid sequence of any one of SEQ ID NOs: 163-168, and (iii) HVR-H3 comprising an amino acid sequence of any one of SEQ ID NOs: 169-174; and (b) a VL domain comprising at least one, at least two, or all three VL HVR sequences selected from (i) HVR-L1 comprising an amino acid sequence of any one of SEQ ID NOs: 175-180, (ii) HVR-L2 comprising an amino acid sequence of any one of SEQ ID NOs: 181-186, and (iii) HVR-L3 comprising an amino acid sequence of any one of SEQ ID NOs: 187-192. In another aspect, the invention provides an antibody comprising (a) HVR-H1 comprising an amino acid sequence of any one of SEQ ID NOs: 157-162; (b) HVR-H2 comprising an amino acid sequence of any one of SEQ ID NOs: 163-168; (c) HVR-H3 comprising an amino acid sequence of any one of SEQ ID NOs: 169-174; (d) HVR-L1 comprising an amino acid sequence of any one of SEQ ID NOs: 175-180; (e) HVR-L2 comprising an amino acid sequence of any one of SEQ ID NOs: 181-186; and (f) HVR-L3 comprising an amino acid sequence of any one of SEQ ID NOs: 187-192. In another aspect, the anti - myostatin antibody comprises a heavy - chain variable domain (VH) sequence that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to any one of the amino acid sequences of SEQ ID NOs: 13, 16 - 30, 32 - 34 and 86 - 95. In some specific embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity, relative to the reference sequence, comprises substitutions (e.g., conservative substitutions), insertions or deletions, but the anti - myostatin antibody comprising that sequence retains the ability to bind to myostatin. In some specific embodiments, in any one of SEQ ID NOs: 13, 16 - 30, 32 - 34 and 86 - 95, a total of 1 to 10 amino acids are substituted, inserted and / or deleted. In some specific embodiments, the substitutions, insertions or deletions occur in regions outside of the HVRs (i.e., in the FRs). Optionally, the anti - myostatin antibody comprises a VH sequence of any one of SEQ ID NOs: 13, 16 - 30, 32 - 34 and 86 - 95 that comprises post - translational modifications of that sequence. In a specific embodiment, the VH comprises one, two or three HVRs selected from: (a) HVR - H1 comprising an amino acid sequence of any one of SEQ ID NOs: 55 - 57, 114 - 115, 126; (b) HVR - H2 comprising an amino acid sequence of any one of SEQ ID NOs: 58 - 60, 116 - 120, 127; and (c) HVR - H3 comprising an amino acid sequence of any one of SEQ ID NOs: 61 - 64, 121, 128. Post - translational modification includes, but is not limited to, modification of the N - terminal glutamine or glutamic acid of the heavy or light chain to pyroglutamic acid by pyroglutamylation. In another aspect, the anti - myostatin antibody comprises a heavy - chain variable domain (VH) sequence that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 13, 16 - 30, 32, 33 and 34. In some specific embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity, relative to the reference sequence, comprises substitutions (e.g., conservative substitutions), insertions or deletions, but the anti - myostatin antibody comprising that sequence retains the ability to bind to myostatin. In some specific embodiments, in any one of SEQ ID NOs: 13, 16 - 30, 32, 33 and 34, a total of 1 to 10 amino acids are substituted, inserted and / or deleted. In some specific embodiments, the substitutions, insertions or deletions occur in regions outside the HVRs (i.e., in the FRs). Optionally, the anti - myostatin antibody comprises a VH sequence of any one of SEQ ID NOs: 13, 16 - 30, 32, 33 and 34, which comprises post - translational modifications of that sequence. In a particular embodiment, the VH comprises one, two or three HVRs selected from: (a) HVR - H1 comprising the amino acid sequence of any one of SEQ ID NOs: 55 - 57, (b) HVR - H2 comprising the amino acid sequence of any one of SEQ ID NOs: 58 - 60, and (c) HVR - H3 comprising the amino acid sequence of any one of SEQ ID NOs: 61 - 64. Post - translational modifications include, but are not limited to, pyroglutamate modification of the N - terminal glutamine or glutamic acid of the heavy or light chain to pyroglutamic acid. In another aspect, the anti - myostatin antibody comprises a heavy - chain variable domain (VH) sequence that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to any one of the amino acid sequences of SEQ ID NOs: 86 - 95. In some specific embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity, relative to the reference sequence, comprises substitutions (e.g., conservative substitutions), insertions or deletions, but the anti - myostatin antibody comprising that sequence retains the ability to bind to myostatin. In some specific embodiments, a total of 1 to 10 amino acids are substituted, inserted and / or deleted in any one of SEQ ID NOs: 86 - 95. In some specific embodiments, the substitutions, insertions or deletions occur in regions outside the HVRs (i.e., in the FRs). Optionally, the anti - myostatin antibody comprises a VH sequence of any one of SEQ ID NOs: 86 - 95 that comprises post - translational modifications of that sequence. In a specific embodiment, the VH comprises one, two or three HVRs selected from: (a) HVR - H1 comprising the amino acid sequence of any one of SEQ ID NOs: 57, 114 - 115, 126; (b) HVR - H2 comprising the amino acid sequence of any one of SEQ ID NOs: 58, 116 - 120, 127; and (c) HVR - H3 comprising the amino acid sequence of any one of SEQ ID NOs: 63, 121, 128. Post - translational modifications include, but are not limited to, pyroglutamination of the N - terminal glutamine or glutamate of the heavy or light chain to pyroglutamate. In another aspect, the anti - myostatin antibody comprises a heavy - chain variable domain (VH) sequence that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 86. In some specific embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity, relative to the reference sequence, comprises substitutions (e.g., conservative substitutions), insertions or deletions, but the anti - myostatin antibody comprising that sequence retains the ability to bind to myostatin. In some specific embodiments, a total of 1 to 10 amino acids are substituted, inserted and / or deleted in SEQ ID NO: 86. In some specific embodiments, the substitutions, insertions or deletions occur in regions outside the HVRs (i.e., in the FRs). Optionally, the anti - myostatin antibody comprises the VH sequence of SEQ ID NO: 86 that comprises post - translational modifications of that sequence.In a particular embodiment, VH comprises one, two, or three HVRs selected from: (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 114, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 63. Post-translational modifications include, but are not limited to, pyroglutamylation of the N-terminal glutamine or glutamate of the heavy or light chain to pyroglutamic acid. In another aspect, the anti-myostatin antibody comprises a heavy chain variable domain (VH) sequence that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 92. In some particular embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the reference sequence comprises substitutions (e.g., conservative substitutions), insertions, or deletions relative to the reference sequence, provided that the anti-myostatin antibody comprising that sequence retains the ability to bind to myostatin. In some particular embodiments, a total of 1 to 10 amino acids in SEQ ID NO: 92 are substituted, inserted, and / or deleted. In some particular embodiments, the substitutions, insertions, or deletions occur in regions outside of the HVRs (i.e., in the FRs). Optionally, the anti-myostatin antibody comprises the VH sequence of SEQ ID NO: 92, which comprises post-translational modifications of that sequence. In a particular embodiment, VH comprises one, two, or three HVRs selected from: (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 114, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 63. Post-translational modifications include, but are not limited to, pyroglutamylation of the N-terminal glutamine or glutamate of the heavy or light chain to pyroglutamic acid. In another aspect, provided are anti - myostatin antibodies, wherein the antibody comprises a VL that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to any of the amino acid sequences of SEQ ID NOs: 15, 31, 35 - 38 and 96 - 99. In some specific embodiments, the VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity, relative to the reference sequence, comprises substitutions (e.g., conservative substitutions), insertions or deletions, but the anti - myostatin antibody comprising that sequence retains the ability to bind to myostatin. In some specific embodiments, in any of SEQ ID NOs: 15, 31, 35 - 38 and 96 - 99, a total of 1 to 10 amino acids are substituted, inserted and / or deleted. In some specific embodiments, the substitutions, insertions or deletions occur in regions outside of the HVRs (i.e., in the FRs). Optionally, the anti - myostatin antibody comprises a VL sequence of any of SEQ ID NOs: 15, 31, 35 - 38 and 96 - 99, which comprises post - translational modifications of that sequence. In a specific embodiment, the VL comprises one, two or three HVRs selected from: (a) HVR - L1 comprising an amino acid sequence of any of SEQ ID NOs: 65 - 69, 122 - 124, 129; (b) HVR - L2 comprising an amino acid sequence of any of SEQ ID NOs: 70 - 72, 125, 130; and (c) HVR - L3 comprising an amino acid sequence of any of SEQ ID NOs: 73 - 74, 131. Post - translational modifications include, but are not limited to, pyroglutamate modification of the N - terminal glutamine or glutamate of the heavy or light chain to pyroglutamate. In another aspect, provided are myostatin antibodies, wherein the antibody comprises a VL that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 15, 31, 35, 36, 37 and 38. In some particular embodiments, the VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity, relative to a reference sequence, comprises substitutions (e.g., conservative substitutions), insertions or deletions, but the myostatin antibody comprising that sequence retains the ability to bind to myostatin. In some particular embodiments, in any one of SEQ ID NOs: 15, 31, 35, 36, 37 and 38, a total of 1 to 10 amino acids are substituted, inserted and / or deleted. In some particular embodiments, the substitutions, insertions or deletions occur in regions outside the HVRs (i.e., in the FRs). Optionally, the myostatin antibody comprises a VL sequence of any one of SEQ ID NOs: 15, 31, 35, 36, 37 and 38, which comprises post-translational modifications of that sequence. In a particular embodiment, the VL comprises one, two or three HVRs selected from: (a) HVR-L1 comprising the amino acid sequence of any one of SEQ ID NOs: 65-69, (b) HVR-L2 comprising the amino acid sequence of any one of SEQ ID NOs: 70-72, and (c) HVR-L3 comprising the amino acid sequence of any one of SEQ ID NOs: 73-74. Post-translational modifications include, but are not limited to, pyroglutamic acid modification of the N-terminal glutamine or glutamic acid of the heavy or light chain to pyroglutamic acid. In another aspect, provided are myostatin antibodies, wherein the antibody comprises a VL that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to any one of the amino acid sequences of SEQ ID NOs: 96 - 99. In some specific embodiments, the VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity, relative to a reference sequence, comprises substitutions (e.g., conservative substitutions), insertions or deletions, but the myostatin antibody comprising that sequence retains the ability to bind to myostatin. In some specific embodiments, in any one of SEQ ID NOs: 96 - 99, a total of 1 to 10 amino acids are substituted, inserted and / or deleted. In some specific embodiments, the substitutions, insertions or deletions occur in regions outside the HVRs. Optionally, the myostatin antibody comprises a VL sequence of any one of SEQ ID NOs: 96 - 99, which comprises post-translational modifications of that sequence. In a specific embodiment, the VL comprises one, two or three HVRs selected from: (a) HVR-L1 comprising an amino acid sequence of any one of SEQ ID NOs: 122 - 124, 129; (b) HVR-L2 comprising an amino acid sequence of any one of SEQ ID NOs: 71, 125, 130; and (c) HVR-L3 comprising an amino acid sequences of SEQ ID NOs: 74, 131. Post-translational modifications include, but are not limited to, pyroglutamate modification of the N-terminal glutamine or glutamate of the heavy or light chain to pyroglutamate. In another aspect, provided are myostatin antibodies, wherein the antibody comprises a VL that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 96. In some specific embodiments, the VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity, relative to a reference sequence, comprises substitutions (e.g., conservative substitutions), insertions or deletions, but the myostatin antibody comprising that sequence retains the ability to bind to myostatin. In some specific embodiments, in SEQ ID NO: 96, a total of 1 to 10 amino acids are substituted, inserted and / or deleted. In some specific embodiments, the substitutions, insertions or deletions occur in regions outside the HVRs. Optionally, the myostatin antibody comprises the VL sequence of SEQ ID NO: 96, which comprises post-translational modifications of that sequence. In a specific embodiment, the VL comprises one, two or three HVRs selected from: (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 122; (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 71; and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 74.Post-translational modifications include, but are not limited to, pyroglutamylation of the N-terminal glutamine or glutamate of the heavy or light chain to pyroglutamic acid. In another aspect, provided is an anti-myostatin antibody, wherein the antibody comprises a VL that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 97. In some specific embodiments, the VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity, relative to the reference sequence, comprises substitutions (e.g., conservative substitutions), insertions or deletions, but the anti-myostatin antibody comprising that sequence retains the ability to bind to myostatin. In some specific embodiments, in SEQ ID NO: 97, a total of 1 to 10 amino acids are substituted, inserted and / or deleted. In some specific embodiments, the substitutions, insertions or deletions occur in regions outside the HVRs. Optionally, the anti-myostatin antibody comprises the VL sequence of SEQ ID NO: 97, which comprises post-translational modifications of that sequence. In a specific embodiment, the VL comprises one, two or three HVRs selected from: (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 123, (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 71, and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 74. Post-translational modifications include, but are not limited to, pyroglutamylation of the N-terminal glutamine or glutamate of the heavy or light chain to pyroglutamic acid. In another aspect, provided is an anti-myostatin antibody, wherein the antibody comprises a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above. In one embodiment, the antibody comprises a VH sequence of any of SEQ ID NOs: 13, 16-30, 32-34 and 86-95 and a VL sequence of any of SEQ ID NOs: 15, 31, 35-38 and 96-99, which comprise post-translational modifications of those sequences. In one embodiment, the antibody comprises a VH sequence of any of SEQ ID NOs: 13, 16-30 and 32-34 and a VL sequence of any of SEQ ID NOs: 15, 31 and 35-38, which comprise post-translational modifications of those sequences. In one embodiment, the antibody comprises a VH sequence of SEQ ID NOs: 86-95, and a VL sequence of SEQ ID NOs: 96-99, which comprise post-translational modifications of those sequences. Post-translational modifications include, but are not limited to, pyroglutamylation of the N-terminal glutamine or glutamate of the heavy or light chain to pyroglutamic acid. In another aspect, an anti - myostatin antibody is provided, wherein the antibody comprises a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above. In one embodiment, the antibody comprises a VH sequence of SEQ ID NO: 86 and a VL sequence of SEQ ID NO: 96, which comprise post - translational modifications of those sequences. In one embodiment, the antibody comprises a VH sequence of SEQ ID NO: 92 and a VL sequence of SEQ ID NO: 97, which comprise post - translational modifications of those sequences. Post - translational modifications include, but are not limited to, pyroglutamate modification of the N - terminal glutamine or glutamate of the heavy or light chain to pyroglutamate. In another aspect, an anti - myostatin antibody is provided, wherein the antibody comprises a VH sequence that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 12, 145 - 150. In some specific embodiments, the VH sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the reference sequence comprises substitutions (e.g., conservative substitutions), insertions or deletions, but the anti - myostatin antibody comprising that sequence retains the ability to bind to myostatin. In some specific embodiments, in any one of SEQ ID NOs: 12, 145 - 150, a total of 1 to 10 amino acids are substituted, inserted and / or deleted. In some specific embodiments, the substitutions, insertions or deletions occur in regions outside the HVRs (i.e., in the FRs). Optionally, the anti - myostatin antibody comprises a VH sequence of any one of SEQ ID NOs: 12, 145 - 150, which comprises post - translational modifications of that sequence. In a specific embodiment, the VH comprises one, two or three HVRs selected from: (a) HVR - H1 comprising the amino acid sequence of any one of SEQ ID NOs: 55, 157 - 162, (b) HVR - H2 comprising the amino acid sequence of any one of SEQ ID NOs: 58, 163 - 168, and (c) HVR - H3 comprising the amino acid sequence of any one of SEQ ID NOs: 61, 169 - 174. Post - translational modifications include, but are not limited to, pyroglutamate modification of the N - terminal glutamine or glutamate of the heavy or light chain to pyroglutamate. In another aspect, provided are myostatin antibodies, wherein the antibody comprises a light chain variable region (VL) that has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to any one of the amino acid sequences of SEQ ID NO: 14, 151 - 156. In some specific embodiments, the VL sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity, relative to the reference sequence, comprises substitutions (e.g., conservative substitutions), insertions or deletions, but the myostatin antibody comprising that sequence retains the ability to bind to myostatin. In some specific embodiments, in any one of SEQ ID NO: 14, 151 - 156, a total of 1 to 10 amino acids are substituted, inserted and / or deleted. In some specific embodiments, the substitutions, insertions or deletions occur in regions outside the HVRs (i.e., in the FRs). Optionally, the myostatin antibody comprises a VL sequence of any one of SEQ ID NO: 14, 151 - 156, which comprises post-translational modifications of that sequence. In a specific embodiment, the VL comprises one, two or three HVRs selected from: (a) HVR-L1 comprising an amino acid sequence of any one of SEQ ID NO: 65, 175 - 180, (b) HVR-L2 comprising an amino acid sequence of any one of SEQ ID NO: 70, 181 - 186, and (c) HVR-L3 comprising an amino acid sequence of any one of SEQ ID NO: 73, 187 - 192. Post-translational modifications include, but are not limited to, pyroglutamic acid modification of the N-terminal glutamine or glutamic acid of the heavy or light chain to pyroglutamic acid. In another aspect, provided are myostatin antibodies, wherein the antibody comprises a VH as in any of the embodiments provided above, and a VL as in any of the embodiments provided above. In one embodiment, the antibody comprises a VH sequence of any one of SEQ ID NO: 12, 145 - 150 and a VL sequence of any one of SEQ ID NO: 14, 151 - 156, respectively, which comprises post-translational modifications of those sequences. Post-translational modifications include, but are not limited to, pyroglutamic acid modification of the N-terminal glutamine or glutamic acid of the heavy or light chain to pyroglutamic acid. In some specific embodiments, the myostatin antibody of the present invention comprises a VH as in any of the embodiments provided above, and a heavy chain constant region comprising an amino acid sequence of any one of SEQ ID NO: 7, 9, 11, 193, 195 - 198, 227, 228, 229 - 381. In some specific embodiments, the myostatin antibody of the present invention comprises a VL as in any of the embodiments provided above, and a light chain constant region comprising an amino acid sequence of any one of SEQ ID NO: 8 and 10. In another aspect, the invention provides an antibody that binds to the same epitope as the anti - myostatin antibodies provided herein. In another aspect, the invention provides an antibody that binds to the same epitope as the antibody described in Table 2a. In another aspect, the invention provides an antibody that binds to the same epitope as the antibody described in Table 11a or 13. In some specific embodiments, the provided antibody binds to an epitope of a fragment of the pro - myostatin peptide consisting of amino acids 21 - 100 of SEQ ID NO: 78. Alternatively, the antibody binds to a fragment of the pro - myostatin peptide consisting of amino acids 21 - 80, 41 - 100, 21 - 60, 41 - 80, 61 - 100, 21 - 40, 41 - 60, 61 - 80, or 81 - 100 of SEQ ID NO: 78. In another aspect, the anti - myostatin antibody according to any of the above embodiments is a monoclonal antibody, including chimeric, humanized, or human antibodies. In one embodiment, the anti - myostatin antibody is an antibody fragment, e.g., Fv, Fab, Fab', scFv, diabody, or F(ab') 2 fragment. In another embodiment, the antibody is a full - length IgG antibody, e.g., a complete IgG1 or IgG4 antibody or other antibody classes or isotypes as defined herein. In another aspect, the anti - myostatin antibody according to any of the above embodiments can singly or combinatorially incorporate any feature as described in Sections 1 - 7 below. 1. Antibody affinity In some specific embodiments, the antibodies provided herein have a dissociation constant (Kd) of ≤1 µm, ≤100 nM, ≤10 nM, ≤1 nM, ≤0.1 nM, ≤0.01 nM, or ≤0.001 nM (e.g., 10 -8 M or less, e.g., from 10 -8 M to 10 -13 M, e.g., from 10 -9 M to 10 -13 M). In one embodiment, the Kd is measured by a radiolabeled antigen binding assay (RIA). In one embodiment, the RIA is performed with the Fab form of the antibody of interest and its antigen. For example, by using the minimum concentration of ( 125I)-Label the antigen-equilibrated Fab, and then capture the bound antigen with a plate coated with anti-Fab antibody to measure the solution binding affinity of the Fab for the antigen (see, e.g., Chen et al., J. Mol. Biol. 293:865 - 881 (1999)). To establish the assay conditions, coat a MICROTITER ® porous plate (Thermo Scientific) overnight with 5 μg / ml capture anti-Fab antibody (Cappel Labs) in 50 mM sodium carbonate (pH 9.6), and then block with 2% (w / v) bovine serum albumin in PBS at room temperature (about 23 °C) for 2 to 5 hours. In a non-adsorbent plate (Nunc #269620), mix 100 pM or 26 pM 125 I]-antigen with serially diluted Fab of interest (e.g., consistent with the evaluation of anti-VEGF antibody, Fab-12 in Presta et al., Cancer Res. 57:4593 - 4599 (1997)). Then incubate the Fab of interest overnight; however, the incubation can be continued for a longer time (e.g., about 65 hours) to ensure equilibrium. Thereafter, transfer the mixture to the capture plate and incubate at room temperature (e.g., 1 hour). Then remove the solution and wash the plate 8 times with PBS containing 0.1% polysorbate 20 (TWEEN-20 ® ). When the plate is dry, add 150 μl / well of scintillation fluid (MICROSCINT-20 TM ; Packard), and count the plate on a TOPCOUNT TM gamma counter (Packard) for 10 minutes. Select the concentration of each Fab that gives less than or equal to 20% of the maximum binding for the competitive binding assay. According to another embodiment, the Kd is measured using BIACORE ® surface plasmon resonance assay. For example, use BIACORE ® -2000 or BIACORE ® -3000 (BIACORE ®, Inc., Piscataway, NJ) was performed at 25 °C on an immobilized antigen CM5 chip at approximately 10 response units (RU). In one embodiment, according to the supplier's instructions, with N-ethyl- N'-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) were used to activate the carboxymethylated dextran biosensor chip (CM5, BIACORE ® , Inc.). Before injecting the coupling protein at a flow rate of 5 μl / min to obtain approximately 10 response units (RU), the antigen was diluted to 5 μg / ml (about 0.2 μM) with 10 mM sodium acetate, pH 4.8. After the injection of the antigen, 1 M ethanolamine was injected to block the unreacted groups. For kinetic measurements, two-fold serial dilutions of Fab (0.78 nM to 500 nM) were injected at 25 °C at a flow rate of approximately 25 μl / min into PBS (PBST) containing 0.05 polysorbate 20 (TWEEN-20 TM ). The binding rate (k ® ) and dissociation rate (k on ) were calculated by simultaneously fitting the binding and dissociation sensorgrams using a simple one-to-one Langmuir binding model (BIACORE off Evaluation Software version 3.2). The equilibrium dissociation constant (Kd) was calculated as the ratio k off / k on . Please refer to, for example, Chen et al., J. Mol. Biol. 293:865-881 (1999). If according to the above surface plasmon resonance assay, the binding rate exceeds 10 6 M -1 s -1, then the association rate is measured using fluorescence quenching techniques, which measure the increase or decrease in the fluorescence emission intensity (excitation = 295 nm; emission = 340 nm, 16 nm bandpass) of 20 nM antigen - antibody (Fab form) in PBS, pH 7.2, at 25°C, in a spectrometer, such as a spectrophotometer (Aviv Instruments) equipped with a stop - flow device or an 8000 series SLM - AMINCO TM spectrophotometer (ThermoSpectronic), in the presence of an increasing concentration of antigen. 2. Antibody fragments In certain embodiments, the antibodies provided herein are antibody fragments. Antibody fragments include, but are not limited to, Fab, Fab', Fab'-SH, F(ab') 2, Fv, and scFv fragments, and other fragments as described below. For a review of specific antibody fragments, see Hudson et al., Nat. Med. 9:129 - 134 (2003). For a review of specific scFv fragments, see, for example, Pluckthün, The Pharmacology of Monoclonal Antibodies, vol. 113, edited by Rosenberg and Moore, (Springer - Verlag, New York), pp. 269 - 315 (1994); also see WO 93 / 16185; and U.S. Patent Nos. 5,571,894 and 5,587,458. Regarding Fab and F(ab') that include salvage receptor - binding epitope residues and have an increased in vivo half - life, see U.S. Patent No. 5,869,046. Diabodies are antibody fragments that have two antigen - binding sites and can be bivalent or bispecific, see, for example, EP 404,097; WO 1993 / 01161; Hudson et al., Nat. Med. 9:129 - 134 (2003); and Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444 - 6448 (1993). Triabodies and tetra - bodies are also described in Hudson et al., Nat. Med. 9:129 - 134 (2003). A single - domain antibody is an antibody fragment that comprises all or part of the heavy - chain variable domain or all or part of the light - chain variable domain of an antibody. In some specific embodiments, the single - domain antibody is a human single - domain antibody (Domantis, Inc., Waltham, MA; see, e.g., U.S. Patent No. 6,248,516 B1). Antibody fragments can be formed by a variety of techniques, including but not limited to proteolytic digestion of intact antibodies, and production by recombinant host cells (e.g., E. coli or phage), as described herein. 3. Chimeric and humanized antibodies In some specific embodiments, the antibodies provided herein are chimeric antibodies. Specific chimeric antibodies are described in, e.g., U.S. Patent No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA 81:6851 - 6855 (1984)). In one example, a chimeric antibody includes a non - human variable region (e.g., a variable region derived from a mouse, rat, rodent, rabbit, or non - human primate, such as a monkey) and a human constant region. In another example, a chimeric antibody is a "class - switched" antibody, in which the class or subclass has been changed from that of the parental antibody. Chimeric antibodies include antigen - binding fragments thereof. In some specific embodiments, the chimeric antibody is a humanized antibody. Generally, non - human antibodies are humanized to reduce their immunogenicity in humans while retaining the specificity and affinity of the parental non - human antibody. In general, a humanized antibody includes one or more variable domains in which the HVRs, e.g., CDRs (or portions thereof), are derived from a non - human antibody, and the FRs (or portions thereof) are derived from a human antibody sequence. A humanized antibody optionally also includes at least a portion of the human constant region. In some embodiments, some FR residues in the humanized antibody are replaced with residues from the corresponding non - human antibody (e.g., the antibody from which the HVR residues are derived), e.g., to restore or enhance antibody specificity or affinity. Reviews of humanized antibodies and methods for preparing them are provided in, e.g., Almagro, Front. Biosci. 13:1619 - 1633 (2008), and are further described in, e.g., Riechmann et al., Nature 332:323 - 329 (1988); Queen et al., Proc. Nat'l Acad. Sci. USA 86:10029-10033 (1989); U.S. Patent Nos. 5,821,337, 7,527,791, 6,982,321 and 7,087,409; Kashmiri et al., Methods 36:25-34 (2005) (describing specific determinant region (SDR) shift); Padlan, Mol. Immunol. 28:489-498 (1991) (describing "surface resurfacing"); Dall'Acqua et al., Methods 36:43-60 (2005) (describing "FR shuffling"); and Osbourn et al., Methods 36:61-68 (2005) and Klimka et al., Br. J. Cancer 83:252-260 (2000) (describing the "directed selection" method of FR shuffling). Human framework regions useful for humanization include, but are not limited to: framework regions selected using the "optimum" method (see, e.g., Sims et al., J. Immunol. 151:2296 (1993); framework regions of consensus sequences of human antibodies from the variable regions of light or heavy chains of a particular subtype (see, e.g., Carter et al., Proc. Natl. Acad. Sci. USA 89:4285 (1992); and Presta et al., J. Immunol. 151:2623 (1993); human mature (somatic mutated) framework regions or human germline framework regions (see, e.g., Almagro and Fransson, Front. Biosci. 13:1619-1633 (2008)); and framework regions derived from screening FR databases (see, e.g., Baca et al., J. Biol. Chem. 272:10678-10684 (1997) and Rosok et al., J. Biol. Chem. 271:22611-22618 (1996)). 4. Human antibodies In some specific embodiments, the antibodies provided herein are human antibodies. Human antibodies can be made using a variety of well-known techniques. Human antibodies are generally described in van Dijk and van de Winkel, Curr. Opin. Pharmacol. 5:368-374 (2001) and Lonberg, Curr. Opin. Immunol. 20:450-459 (2008). Human antibodies can be prepared by administering an immunogen to a transgenic animal that has been modified to produce a complete human antibody or a complete antibody with a human variable region in response to antigen challenge. Such animals generally contain all or part of the human immunoglobulin locus, which replaces the endogenous immunoglobulin locus, or which is present extrachromosomally or integrated randomly into the animal's chromosomes. In such transgenic mice, the endogenous immunoglobulin locus is generally inactivated. For a review of methods for obtaining human antibodies from transgenic animals, see Lonberg, Nat. Biotech. 23:1117-1125 (2005). See also, e.g., U.S. Patent Nos. 6,075,181 and 6,150,584, which describe the XENOMOUSE TM technology; U.S. Patent No. 5,770,429, which describes the HuMab® technology; U.S. Patent No. 7,041,870, which describes the K-M MOUSE® technology, and U.S. Patent Publication No. US 2007 / 0061900, which describes the VelociMouse® technology). The human variable regions of the complete antibodies produced by such animals can be further modified, e.g., by combining with different human constant regions. Human antibodies can also be formed by a hybridoma-based method. Human myeloma and mouse-human hybrid myeloma cell lines for the production of human monoclonal antibodies have been described. (See, e.g., Kozbor, J. Immunol. 133:3001 (1984); Brodeur et al., Monoclonal antibody Production Techniques and Applications, pp. 51-63 (Marcel Dekker, Inc., New York, 1987); and Boerner et al., J. Immunol. 147:86 (1991). Human antibodies produced by the human B cell hybridoma technique are also described in Li et al., as described in Proc. Natl. Acad. Sci. USA 103:3557-3562 (2006). Other methods include those described in, for example, U.S. Patent No. 7,189,826 (describing the production of monoclonal human IgM antibodies from hybridoma cell lines) and Ni, Xiandai Mianyixue 26(4):265-268 (2006) (describing human-human hybridomas). The human hybridoma technology (Trioma technology) is also described in Vollmers and Brandlein, Histology and Histopathology 20(3):927-937 (2005) and Vollmers and Brandlein, Methods and Findings in Experimental and Clinical Pharmacology 27(3):185-191 (2005). Human antibodies can also be generated by isolating Fv strain variable domain sequences selected from a human phage display library. Such variable domain sequences can then be combined with the desired human constant domains. Techniques for selecting human antibodies from antibody libraries are described below. 5. Antibodies from libraries The antibodies of the present invention can be isolated by screening a combinatorial library for antibodies having the desired activity. For example, a variety of methods are known in the art for generating phage display libraries and screening such libraries for antibodies having the desired binding characteristics. Such methods are reviewed in, for example, Hoogenboom et al., Methods in Molecular Biology 178:1-37 (2000); edited by O'Brien et al., Human Press, Totowa, NJ, 2001, and further in, for example, McCafferty et al., Nature 348:552-554; Clackson et al., Nature 352:624-628 (1991); Marks et al., J. Mol. Biol. 222:581-597 (1992); Marks and Bradbury, M Methods in Molecular Biology 248:161-175 (Lo, ed., Human Press, Totowa, NJ, 2003); Sidhu et al., J. Mol. Biol. 338(2):299-310 (2004); Lee et al., J. Mol. Biol. 340(5):1073-1093 (2004); Fellouse, Proc. Natl. Acad. Sci. USA 101(34):12467-12472 (2004); and Lee et al., described in J. Immunol. Methods 284(1-2):119-132 (2004). In certain phage display methods, repertoires of VH and VL genes are cloned separately by polymerase chain reaction (PCR) and randomly recombined in a phage library, after which antigen-binding phages can be screened therein as described by Winter et al., Ann. Rev. Immunol. 12:433-455 (1994). Phages typically present antibody fragments in the form of single-chain Fv (ScFv) fragments or Fab fragments. Databases from immunized sources can provide high-affinity antibodies to immunogens without the need to construct hybridomas. Alternatively, naive libraries can be cloned (e.g., from humans) to provide a single source of antibodies against a wide range of non-self and self antigens without any immunization, as described by Griffiths et al., EMBO J, 12:725-734 (1993). Finally, naive libraries can also be synthetically generated by transfecting unrearranged V gene segments from stem cells and using PCR primers containing random sequences to encode highly variable CDR3 regions, and effecting in vitro rearrangement, as described by Hoogenboom and Winter, As described in J. Mol. Biol. 227:381-388 (1992). Patent publications describing human antibody phage display libraries include, for example: U.S. Patent No. 5,750,373, and U.S. Patent Publication Nos. 2005 / 0079574, 2005 / 0119455, 2005 / 0266000, 2007 / 0117126, 2007 / 0160598, 2007 / 0237764, 2007 / 0292936, and 2009 / 0002360. Antibodies or antibody fragments isolated from human antibody libraries are considered human antibodies or human antibody fragments herein. 6. Bispecific antibodies In certain embodiments, the antibodies provided herein are bispecific antibodies, e.g., bispecific antibodies. Bispecific antibodies are monoclonal antibodies that have binding specificity for at least two different epitopes. In certain embodiments, one of the binding specificities is for myostatin and the other is for any other antigen. In certain embodiments, the bispecific antibody can bind to two different epitopes of myostatin. Bispecific antibodies can also be used to localize cytotoxic agents to cells expressing myostatin. Bispecific antibodies can be produced as full-length antibodies or antibody fragments. Techniques for making bispecific antibodies include, but are not limited to, recombinant co-expression of two immunoglobulin heavy chain-light chain pairs having different specificities (see Milstein and Cuello, Nature 305:537 (1983)), WO 1993 / 08829, and Traunecker et al., EMBO J. 10:3655 (1991)), and "knob-in-hole" engineering (see, e.g., U.S. Patent No. 5,731,168). Bispecific antibodies can also be produced by engineering electrostatic steering for the preparation of antibody Fc-heterodimeric molecules (WO 2009 / 089004A1); cross-linking two or more antibodies or fragments (see, e.g., U.S. Patent No. 4,676,980, and Brennan et al., Science, 229:81 (1985)); using leucine zippers to generate bispecific antibodies (see, e.g., Kostelny et al., J. Immunol. 148(5):1547-1553 (1992)); using the "diabody" technology to generate bispecific antibody fragments (see, e.g., Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993)); and the use of single-chain Fv (sFv) dimers (see, e.g., Gruber et al., J. Immunol. 152:5368 (1994)); and the preparation of trispecific antibodies, such as, e.g., Tutt et al., J. Immunol. 147:60 (1991). Also included herein are engineered antibodies having three or more functional antigen-binding sites, including "Octopus antibodies" (see, e.g., US 2006 / 0025576A1). The antibodies or fragments herein also include "dual action FAb" or "DAF", which include antigen-binding sites that bind to myostatin and another distinct antigen (see, e.g., US 2008 / 0069820). 7. Antibody variants In certain embodiments, amino acid sequence variants of the antibodies provided herein are contemplated. For example, it may be desirable to improve the binding affinity and / or other biological properties of the antibody. Amino acid sequence variants of the antibody can be prepared by introducing appropriate modifications into the nucleotide sequence encoding the antibody, or by peptide synthesis. Such modifications include, for example, deleting, and / or inserting and / or substituting residues within the amino acid sequence of the antibody. Any combination of deletions, insertions and substitutions can be made to the final construct, provided that the final construct has the desired characteristics, e.g., antigen binding. a. Substitution, insertion and deletion variants In certain embodiments, antibody variants having one or more amino acid substitutions are provided. Positions of interest for substitution mutagenesis include the HVRs and FRs. Conservative substitutions are shown under the heading "Preferred Substitutions" in Table 1. More substantial changes are provided under the heading "Exemplary Substitutions" in Table 1 and are further described below with reference to amino acid side chain classes. Amino acid substitutions can be introduced into the antibody of interest and the products screened for the desired activity, e.g., retained / improved antibody binding, reduced immunogenicity, or improved ADCC or CDC. [Table 1] Amino acids can be classified according to common side-chain characteristics into: (1) hydrophobic: norleucine, Met, Ala, Val, Leu, Ile; (2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gln; (3) acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) residues that affect chain orientation: Gly, Pro; and (6) aromatic: Trp, Tyr, Phe. Non-conservative substitutions will result in the exchange of a member of one of these groups for a member of another group. One class of substitution variants involves substituting one or more residues of a hypervariable region of a parental antibody (e.g., a humanized or human antibody). Generally, the variants generated for further study will have a modification (e.g., improvement) relative to the parental antibody in a particular biological property (e.g., increased affinity, decreased immunogenicity) and / or will have a particular biological property of the parental antibody substantially retained. Exemplary substitution variants are affinity matured antibodies, which can be conveniently generated, e.g., using phage display-based affinity maturation techniques such as those described herein. Briefly, one or more HVR residues are mutated and the variant antibody is displayed on a phage, and screened for a particular biological activity (e.g., binding affinity). Modifications (e.g., substitutions) can be made in the HVRs, e.g., to improve antibody affinity. Such modifications can be made in HVR "hot spots", i.e., residues encoded by codons that undergo mutation at high frequency during somatic maturation (see, e.g., Chowdhury, Methods Mol. Biol. 207:179-196 (2008), and / or residues that contact the antigen, and the binding affinity of the resulting variant VH or VL is tested. Affinity maturation by construction and reselection from a second library has been described, e.g., in Hoogenboom et al., Methods in Molecular Biology 178:1-37 (edited by O'Brien et al., Human Press, Totowa, NJ, (2001). In some embodiments of affinity maturation, diversity is introduced into the variable gene selected for maturation by any of a variety of methods (e.g., error-prone PCR, chain shuffling, or oligonucleotide-directed mutagenesis). A second library is then generated. The library is then screened to identify any antibody variants having the desired affinity. Another method of introducing diversity involves HVR-directed methods, where several HVR residues (e.g., 4 to 6 residues at a time) are randomized. HVR residues involved in antigen binding can be specifically identified, e.g., using alanine scanning mutagenesis or modeling. CDR-H3 and CDR-L3 are particularly often targeted. In some specific embodiments, substitutions, insertions or deletions can occur within one or more HVRs, provided that such modifications do not substantially reduce the ability of the antibody to bind antigen. For example, conservative modifications (such as the conservative substitutions provided herein) that do not substantially reduce the binding affinity can be made in the HVRs. Such modifications can, for example, be outside of the antigen - contacting residues in the HVRs. In the specific embodiments of the variant VH and VL sequences provided above, each HVR is either unmodified or contains no more than one, two or three amino acid substitutions. A method for identifying residues or regions of an antibody that can be targeted for mutagenesis is called "alanine - scanning mutagenesis", as described by Cunningham and Wells, (1989) Science, 244:1081 - 1085. In this method, residues or a group of residues (e.g., charged residues such as arg, asp, his, lys and glu) can be identified and replaced with neutral or negatively charged amino acids (e.g., alanine or polyalanine) to determine whether it affects the interaction between the antibody and the antigen. Additional substitutions can be introduced at amino acid positions that show sensitivity to the initial substitution. Alternatively, or additionally, the crystal structure of the antigen - antibody complex can be analyzed to identify the contact points between the antibody and the antigen. Such contact residues and adjacent residues can be targeted or eliminated as candidates for substitution. Variants can be screened to determine whether they possess the desired properties. Amino acid sequence insertions include amino - and / or carboxyl - terminal fusions of polypeptides ranging in length from one residue to polypeptides containing 100 or more residues, as well as insertions within the sequence of single or multiple amino acid residues. Examples of terminal insertions include antibodies having an N - terminal methionyl residue. Other insertion variants of antibody molecules include fusions of the N or C terminus of the antibody to an enzyme (e.g., ADEPT) or a polypeptide, which increases the serum half - life of the antibody. b. Glycosylation variants In some specific embodiments, the antibodies provided herein are modified to increase or decrease the degree to which the antibody is glycosylated. Addition or deletion of glycosylation sites on the antibody can be conveniently accomplished by modifying the amino acid sequence such that one or more glycosylation sites are created or removed. When the antibody includes an Fc region, the sugars attached thereto can be modified. Naturally - produced antibodies from mammalian cells typically include branched, biantennary oligosaccharides that are generally attached by N - linkage to Asn297 in the CH2 domain of the Fc region. See, for example, Wright et al. TIBTECH 15:26 - 32 (1997). Oligosaccharides can contain multiple sugars such as mannose, N-acetylglucosamine (GlcNAc), galactose, and sialic acid, as well as fucose attached to GlcNAc in the "backbone" of the biantennary oligosaccharide structure. In some embodiments, the oligosaccharides in the antibodies of the present invention can be modified to generate antibody variants with specific improved properties. In one embodiment, the provided antibody variant has a sugar structure that lacks fucose attached (directly or indirectly) to the Fc region. For example, the amount of fucose in such antibodies can be from 1% to 80%, from 1% to 65%, from 5% to 65%, or from 20% to 40%. The amount of fucose is determined by calculating the average amount of fucose at Asn297 within the sugar chain, relative to the sum of all glycan structures attached to Asn297 as measured by MALDI-TOF mass spectrometry (e.g., complex, hybrid, and high-mannose structures), for example, as described in WO 2008 / 077546. Asn297 refers to the asparagine residue located at approximately position 297 (Eu numbering of Fc region residues); however, due to minor sequence variations in the antibody, Asn297 can also be located approximately ±3 amino acids upstream or downstream of position 297, i.e., between positions 294 and 300. Such fucosylated variants can have improved ADCC function, see, for example, US Patent Publication No. 2003 / 0157108 (Presta, L.); 2004 / 0093621 (Kyowa Hakko Kogyo Co., Ltd). Examples of publications related to "defucosylated" or "fucose-deficient" antibody variants include: US 2003 / 0157108; WO 2000 / 61739; WO 2001 / 29246; US 2003 / 0115614; US 2002 / 0164328; US 2004 / 0093621; US 2004 / 0132140; US 2004 / 0110704; US 2004 / 0110282; US 2004 / 0109865; WO 2003 / 085119; WO 2003 / 084570; WO 2005 / 035586; WO 2005 / 035778; WO 2005 / 053742; WO 2002 / 031140; Okazaki et al., J. Mol. Biol. 336:1239 - 1249 (2004); Yamane-Ohnuki et al., Biotech. Bioeng. 87:614 (2004). Examples of cell lines capable of producing afucosylated antibodies include Lec13 CHO cells lacking protein fucosylation (Ripka et al., Arch. Biochem. Biophys. 249:533-545 (1986); US Patent Publication No. 2003 / 0157108 A1, Presta, L; and WO 2004 / 056312, Adams et al., particularly in Example 11), and knockout cell lines, such as the α-1,6-fucosyltransferase gene, FUT8, knockout CHO cells (see, e.g., Yamane-Ohnuki et al., Biotech. Bioeng. 87:614 (2004); Kanda et al., Biotechnol. Bioeng. 94(4):680-688 (2006); and WO2003 / 085107). Also provided are antibody variants having bisected oligosaccharides, e.g., wherein the biantennary oligosaccharide attached to the antibody Fc region is bisected by GlcNAc. Such antibody variants may have reduced fucosylation and / or improved ADCC function. Examples of such antibody variants are described in, e.g., WO 2003 / 011878 (Jean-Mairet et al.), US Patent No. 6,602,684 (Umana et al.); and US 2005 / 0123546 (Umana et al.). Antibody variants having at least one galactose residue in the oligosaccharide attached to the Fc region are also provided. Such antibody variants may have improved CDC function. Such antibody variants are described in, e.g., WO 1997 / 30087 (Patel et al.); W0 1998 / 58964 (Raju, S); and WO 1999 / 22764 (Raju, S). c. Fc region variants In some specific embodiments, one or more amino acid modifications can be introduced into the Fc region of the antibodies provided herein, thereby generating Fc region variants. Fc region variants can include human Fc region sequences (e.g., human IgG1, IgG2, IgG3, or IgG4 Fc regions) that include amino acid modifications (e.g., substitutions) at one or more amino acid positions. In certain embodiments, the invention contemplates antibody variants that have some but not all effector functions, making them ideal candidates for applications where the in vivo half-life of the antibody is important, yet specific effector functions, such as complement and ADCC, are unnecessary or harmful. In vitro and / or in vivo cytotoxicity assays can be performed to confirm the reduction / abrogation of CDC and / or ADCC activity. For example, Fc receptor (FcR) binding assays can be performed to ensure that the antibody lacks FcγR binding (and thus may lack ADCC activity), but retains FcRn binding ability. The major cells that mediate ADCC, NK cells, express only FcγRIII, whereas monocytes express FcγRI, FcγRII, and FcγRIII. FcR expression on hematopoietic cells is summarized in Ravetch and Kinet, Table 3 on page 464 of Annu. Rev. Immunol. 9:457-492 (1991). Non-limiting examples of in vitro assays for assessing the ADCC activity of a molecule of interest are described in U.S. Patent No. 5,500,362 (see, e.g., Hellstrom et al., Proc. Nat'l Acad. Sci. USA 83:7059-7063 (1986)) and Hellstrom, I et al., Proc. Nat'l Acad. Sci. USA 82:1499-1502 (1985); U.S. Patent No. 5,821,337 (see, Bruggemann et al., J. Exp. Med. 166:1351-1361 (1987)). Alternatively, non-radioactive assays can be employed (see, e.g., ACTI™ Non-Radioactive Cytotoxicity Assay for flow cytometry (CellTechnology, Inc. Mountain View, CA); and CytoTox 96 ® Non-Radioactive Cytotoxicity Assay (Promega, Madison, WI)). Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC) and natural killer (NK) cells. Alternatively, or additionally, the ADCC activity of a molecule of interest can be evaluated in vivo, e.g., in an animal model, such as Clynes et al., Disclosed in Proc. Nat'l Acad. Sci. USA 95:652-656 (1998). A Clq binding assay can also be performed to determine that the antibody cannot bind Clq and thus lacks CDC activity. See, e.g., Clq and C3c binding ELISAs in WO 2006 / 029879 and WO 2005 / 100402. To assess complement activation, a CDC assay can be performed (see, e.g., Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996); Cragg et al., Blood 101:1045-1052 (2003); and Cragg, Blood 103:2738-2743 (2004)). FcRn binding and in vivo clearance / half-life assays can also be performed using methods known in the art (see, e.g., Petkova et al., Int'l. Immunol. 18(12):1759-1769 (2006)). Antibodies with reduced effector function include those antibodies having substitutions in one or more of residues 238, 265, 269, 270, 297, 327, and 329 in the Fc region (U.S. Patent No. 6,737,056). Such Fc mutants include Fc mutants having substitutions in two or more of amino acid positions 265, 269, 270, 297, and 327, including the so-called "DANA" Fc mutant having residues 265 and 297 substituted with alanine (U.S. Patent No. 7,332,581). Certain antibody variants with improved or attenuated binding to FcRs have been described (see, e.g., U.S. Patent No. 6,737,056; WO 2004 / 056312; and Shields et al., J. Biol. Chem. 9(2):6591-6604 (2001)). In certain embodiments, the antibody variant includes an Fc region having one or more amino acid substitutions that enhance ADCC, e.g., substitutions at positions 298, 333, and / or 334 (EU numbering of residues) in the Fc region. In some embodiments, alterations are made in the Fc region that result in altered (i.e., improved or attenuated) Clq binding and / or complement-dependent cytotoxicity (CDC), e.g., as in U.S. Patent No. 6,194,551, WO 1999 / 51642, and Idusogie et al., as described in J. Immunol. 164:4178-4184 (2000). Antibodies having increased half-life and improved binding to the neonatal Fc receptor (FcRn), which is responsible for transporting maternal IgG to the fetus (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994)), are described in US2005 / 0014934 A1 (Hinton et al.). Those antibodies include antibodies having one or more substitutions in the Fc region thereof that improve the binding of the Fc region to FcRn. Such Fc variants include those having substitutions at one or more of the Fc region residues: 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or 434, such as a substitution at Fc region residue 434 (U.S. Patent No. 7,371,826). For other examples of Fc region variants, see also Duncan, Nature 322:738-40 (1988); U.S. Patent Nos. US 5,648,260 and US 5,624,821; and WO 1994 / 29351. d) Cysteine-modified antibody variants J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994)). Those antibodies include antibodies having one or more substitutions in the Fc region thereof that improve the binding of the Fc region to FcRn. Such Fc variants include those having substitutions at one or more of the Fc region residues: 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or 434, such as a substitution at Fc region residue 434 (U.S. Patent No. 7,371,826). For other examples of Fc region variants, see also Duncan, Nature 322:738-40 (1988); U.S. Patent Nos. US 5,648,260 and US 5,624,821; and WO 1994 / 29351. d) Cysteine-modified antibody variants In certain embodiments, it is desirable to generate cysteine-modified antibodies, e.g., “thioMAbs,” in which one or more residues of the antibody are replaced with cysteine residues. In particular embodiments, the residues to be replaced are in accessible positions on the antibody. By replacing those residues with cysteine, reactive thiol groups are placed in accessible positions on the antibody and can be used to couple the antibody to other moieties, such as a drug moiety or linker-drug moiety, to create an immunoconjugate, as further described herein. In certain embodiments, any one or more of the following residues can be replaced with cysteine: V205 (Kabat numbering) of the light chain; A118 (EU numbering) of the heavy chain; and S400 (EU numbering) of the heavy chain Fc region. Cysteine-modified antibodies can be generated, for example, as described in U.S. Patent No. 7,521,541. e) Antibody derivatives In some specific embodiments, the antibodies provided herein can be further modified to include additional non-protein moieties known and readily available in the art. Moieties suitable for antibody derivatization include, but are not limited to, water-soluble polymers. Non-limiting examples of water-soluble polymers include, but are not limited to, polyethylene glycol (PEG), copolymers of ethylene glycol / propanediol, carboxymethyl cellulose, dextran, polyvinyl alcohol, polyvinylpyrrolidone, poly-1,3-dioxolane, poly-1,3,6-tri (poly-1,3,6-trioxane), ethylene / maleic anhydride copolymer, polyamino acids (homopolymers or random copolymers), and dextran or poly(n-vinylpyrrolidone) polyethylene glycol, polypropylene glycol homopolymer, polypropylene oxide / ethylene oxide copolymer, poly(ethylene glycol)ylated polyols (e.g., glycerol), polyvinyl alcohol, and mixtures thereof. Polyethylene glycol propionaldehyde may have advantages in production due to its stability in water. The polymer can have any molecular weight and can be branched or unbranched. The number of polymers attached to the antibody can vary, and if more than one polymer is attached, they can be the same or different molecules. Generally, the quantity and / or type of polymer used for derivatization can be determined based on, including but not limited to, considering the particular properties or functions of the antibody to be improved, whether the antibody derivative will be used for therapy under defined conditions, etc. In another embodiment, a conjugate of an antibody and a non-protein moiety that can be selectively heated by exposure to radiation is provided. In one embodiment, the non-protein moiety is a carbon nanotube (Kam et al., Proc. Natl. Acad. Sci. USA 102:11600-11605 (2005)). The radiation can have any wavelength and includes, but is not limited to, wavelengths that do not harm normal cells but heat the non-protein moiety to a temperature close to that at which cells of the antibody-non-protein moiety conjugate are killed. 8. Variant Fc region In one aspect, the invention provides an isolated polypeptide that includes a variant Fc region having enhanced FcγRIIb binding activity. In some aspects, the polypeptide is an antibody. In some aspects, the polypeptide is an Fc fusion protein. In some specific embodiments, the variant Fc region includes at least one amino acid residue modification (e.g., substitution) compared to the corresponding sequence in the Fc region of a native or reference variant sequence (generally collectively referred to herein as the "parent" Fc region). In some specific embodiments, the variant Fc region of the invention has increased binding activity to monkey FcγRIIb compared to the parent Fc region. In some specific embodiments, the monkey FcγRIIb is rhesus monkey FcγRIIb (sequence identifier: 223). In some specific embodiments, the ratio of [KD value of the parental Fc region for monkey FcγRIIb] / [KD value of the variant Fc region for monkey FcγRIIb] can be 2.0 or greater, 3.0 or greater, 4.0 or greater, 5.0 or greater, 6.0 or greater, 7.0 or greater, 8.0 or greater, 9.0 or greater, 10 or greater, 15 or greater, 20 or greater, 25 or greater, 30 or greater, 40 or greater, or 50 or greater. In some other embodiments, the variant Fc region has reduced binding activity to monkey FcγRIIIa. In some specific embodiments, the ratio of [KD value of the parental Fc region for monkey FcγRIIIa] / [KD value of the variant Fc region for monkey FcγRIIIa] can be 0.50 or less, 0.40 or less, 0.30 or less, 0.20 or less, 0.10 or less, 0.09 or less, 0.08 or less, 0.07 or less, 0.06 or less, 0.05 or less, 0.04 or less, 0.03 or less, 0.02 or less, or 0.01 or less. In some specific embodiments, monkey FcγRIIb has the sequence of SEQ ID NO: 223 (rhesus monkey). In some specific embodiments, monkey FcγRIIIa has the sequence of SEQ ID NO: 224 (rhesus monkey). In some other embodiments, the variant Fc region has enhanced binding activity to human FcγRIIb. In some specific embodiments, the ratio of [KD value of the parental Fc region for human FcγRIIb] / [KD value of the variant Fc region for human FcγRIIb] can be 2.0 or greater, 3.0 or greater, 4.0 or greater, 5.0 or greater, 6.0 or greater, 7.0 or greater, 8.0 or greater, 9.0 or greater, 10 or greater, 15 or greater, 20 or greater, 25 or greater, 30 or greater, 40 or greater, or 50 or greater. In some other embodiments, the variant Fc region has reduced binding activity to human FcγRIIIa. In some specific embodiments, the ratio of [KD value of the parental Fc region for human FcγRIIIa] / [KD value of the variant Fc region for human FcγRIIIa] can be 0.50 or less, 0.40 or less, 0.30 or less, 0.20 or less, 0.10 or less, 0.09 or less, 0.08 or less, 0.07 or less, 0.06 or less, 0.05 or less, 0.04 or less, 0.03 or less, 0.02 or less, or 0.01 or less. In some specific embodiments, human FcγRIIb has the sequence of SEQ ID NO: 212, 213, or 214. In some specific embodiments, human FcγRIIIa has the sequence of SEQ ID NO: 215, 216, 217, or 218. In still other embodiments, the variant Fc region has lower binding activity to human FcγRIIa (H type) than to human FcγRIIb. In some specific embodiments, the ratio of [KD value of the parental Fc region for human FcγRIIa (H type)] / [KD value of the variant Fc region for human FcγRIIa (H type)] can be 5.0 or less, 4.0 or less, 3.0 or less, 2.0 or less, 1.0 or less, 0.9 or less, 0.8 or less, 0.7 or less, 0.6 or less, 0.5 or less, 0.4 or less, 0.3 or less, 0.2 or less, or 0.1 or less. In still other embodiments, the variant Fc region has lower binding activity to human FcγRIIa (R type) than to human FcγRIIb. In some specific embodiments, the ratio of [KD value of the parental Fc region for human FcγRIIa (R type)] / [KD value of the variant Fc region for human FcγRIIa (R type)] can be 5.0 or less, 4.0 or less, 3.0 or less, 2.0 or less, 1.0 or less, 0.9 or less, 0.8 or less, 0.7 or less, 0.6 or less, 0.5 or less, 0.4 or less, 0.3 or less, 0.2 or less, or 0.1 or less. In some specific embodiments, human FcγRIIa (H type) has the sequence of SEQ ID NO: 211. In some specific embodiments, human FcγRIIa (R type) has the sequence of SEQ ID NO: 210. In some specific embodiments, the ratio of [KD value of the parental Fc region for monkey FcγRIIa] / [KD value of the variant Fc region for monkey FcγRIIa] can be 2.0 or greater, 3.0 or greater, 4.0 or greater, 5.0 or greater, 6.0 or greater, 7.0 or greater, 8.0 or greater, 9.0 or greater, 10 or greater, 15 or greater, 20 or greater, 25 or greater, 30 or greater, 40 or greater, or 50 or greater. In some specific embodiments, monkey FcγRIIa is selected from: monkey FcγRIIa1 (e.g., rhesus monkey FcγRIIa1 (SEQ ID NO: 220)), monkey FcγRIIa2 (e.g., rhesus monkey FcγRIIa2 (SEQ ID NO: 221)), and monkey FcγRIIa3 (e.g., rhesus monkey FcγRIIa3 (SEQ ID NO: 222)). In another embodiment, the KD value of the variant Fc region for monkey FcγRIIb can be 1.0×10 -6 M or less, 9.0×10 -7 M or less, 8.0×10 -7 M or less, 7.0×10 -7 M or less, 6.0×10 -7 M or less, 5.0×10 -7 M or less, 4.0×10 -7 M or less, 3.0×10 -7 M or less, 2.0×10 -7 M or less, or 1.0×10 -7 M or less. In another embodiment, the KD value of the mutant Fc region for monkey FcγRIIIa can be 5.0×10 -7 M or greater, 6.0×10 -7 M or greater, 7.0×10 -7 M or greater, 8.0×10 -7 M or greater, 9.0×10 -7 M or greater, 1.0×10 -6 M or greater, 2.0×10 -6 M or greater, 3.0×10 -6 M or greater, 4.0×10 -6 M or greater, 5.0×10 -6 M or greater, 6.0×10 -6 M or greater, 7.0×10 -6 M or greater, 8.0×10 -6 M or greater, 9.0×10 -6 M or greater, or 1.0×10 -5 M or greater. In another embodiment, the KD value of the mutant Fc region for human FcγRIIb can be 2.0×10 -6 M or less, 1.0×10 -6 M or less, 9.0×10 -7 M or less, 8.0×10 -7 M or less, 7.0×10 -7 M or less, 6.0×10 -7 M or less, 5.0×10 -7 M or less, 4.0×10 -7 M or less, 3.0×10 -7 M or less, 2.0×10 -7 M or less, or 1.0×10 -7 M or less. In another embodiment, the KD value of the variant Fc region for human FcγRIIIa can be 1.0×10 -6 M or greater, 2.0×10 -6 M or greater, 3.0×10 -6 M or greater, 4.0×10 -6 M or greater, 5.0×10 -6 M or greater, 6.0×10 -6 M or greater, 7.0×10 -6 M or greater, 8.0×10 -6 M or greater, 9.0×10 -6 M or greater, 1.0×10 -5 M or greater, 2.0×10 -5 M or greater, 3.0×10 -5 M or greater, 4.0×10 -5 M or greater, or 5.0×10 -5 M or greater. In another embodiment, the KD value of the variant Fc region for human FcγRIIa (H type) can be 1.0×10 -7 M or greater, 2.0×10 -7 M or larger, 3.0×10 -7 M or larger, 4.0×10 -7 M or larger, 5.0×10 -7 M or larger, 6.0×10 -7 M or larger, 7.0×10 -7 M or larger, 8.0×10 -7 M or larger, 9.0×10 -7 M or larger, 1.0×10 -6 M or larger, 2.0×10 -6 M or larger, 3.0×10 -6 M or larger, 4.0×10 -6 M or larger, or 5.0×10 -6 In another embodiment, the KD value of the variant Fc region for human FcγRIIa (R type) may be 2.0×10 -7 M or larger, 3.0×10 -7 M or larger, 4.0×10 -7 M or larger, 5.0×10 -7 M or larger, 6.0×10 -7 M or larger, 7.0×10 -7 M or larger, 8.0×10 -7 M or larger, 9.0×10 -7 M or larger, 1.0×10 -6 M or larger, 2.0×10 -6 M or larger, 3.0×10 -6 M or larger, 4.0×10 -6 M or larger, or 5.0×10 -6 M or greater. In another embodiment, the KD value of the variant Fc region for monkey FcγRIIa can be 1.0×10 -6 M or less, 9.0×10 -7 M or less, 8.0×10 -7 M or less, 7.0×10 -7 M or less, 6.0×10 -7 M or less, 5.0×10 -7 M or less, 4.0×10 -7 M or less, 3.0×10 -7 M or less, 2.0×10 -7 M or less, or 1.0×10 -7 M or less. In some specific embodiments, monkey FcγRIIa can be selected from any one of monkey FcγRIIa1, monkey FcγRIIa2, and monkey FcγRIIa3. When developing pharmaceutical products for treating human diseases, due to the biological proximity between monkeys and humans, it is important to evaluate its efficacy and safety in monkeys. From this perspective, the pharmaceutical product to be developed preferably has cross-reactivity with both humans and monkeys in terms of the target binding activity. "Fcγ receptor" (referred to herein as Fcγ receptor, FcγR or FcgR) refers to a receptor that can bind to the Fc region of IgG1, IgG2, IgG3, and IgG4 monoclonal antibodies and actually represents any member of the protein family encoded by the Fcγ receptor gene. In humans, this family includes FcγRI (CD64), which includes isoforms FcγRIa, FcγRIb, and FcγRIc; FcγRII (CD32), which includes isoforms FcγRIIa (including allotypes H131 (H-type) and R131 (R-type)), FcγRIIb (including FcγRIIb-1 and FcγRIIb-2), and FcγRIIc; and FcγRIII (CD16), which includes isoforms FcγRIIIa (including allotypes V158 and F158) and FcγRIIIb (including allotypes FcγRIIIb-NA1 and FcγRIIIb-NA2), and any FcγRs, FcγR isoforms, or allotypes not yet discovered, but not limited to these. It has been reported that FcγRIIb1 and FcγRIIb2 are splice variants of human FcγRIIb. In addition, a splice variant named FcγRIIb3 has been reported (J Exp Med, 1989, 170: 1369-1385). In addition to these splice variants, human FcγRIIb includes all splice variants registered in NCBI, which are NP_001002273.1, NP_001002274.1, NP_001002275.1, NP_001177757.1, and NP_003992.3. In addition, human FcγRIIb includes each previously reported genetic polymorphism of FcγRIIb as well as FcγRIIb ( Arthritis Rheum. 48:3242-3252 (2003); Kono et al., Hum. Mol. Genet. 14:2881-2892 (2005); and Kyogoju et al., Arthritis Rheum. 46:1242-1254 (2002)) and each genetic polymorphism to be reported in the future. In FcγRIIa, there are two allotypes, one FcγRIIa has histidine at amino acid position 131 (H-type), and the other has arginine substituted at amino acid position 131 (R-type) (Warrmerdam, J. Exp. Med.172:19-25 (1990)). FcγRs include, but are not limited to, FcγRs derived from humans, mice, rats, rabbits, and monkeys, and can be derived from any organism. Mouse FcγRs include FcγRI (CD64), FcγRII (CD32), FcγRIII (CD16), and FcγRIII-2 (CD16-2), and any mouse FcγR or FcγR isoform, but are not limited to these. Unless otherwise specified, the term "monkey FcγR" or variations thereof refers to rhesus monkey FcγRIIa1 (SEQ ID NO: 220), FcγRIIa2 (SEQ ID NO: 221), FcγRIIa3 (SEQ ID NO: 222), FcγRIIb (SEQ ID NO: 223), or FcγRIIIaS (SEQ ID NO: 224). The polynucleotide sequence of human FcγRI is shown in SEQ ID NO: 199 (NM_000566.3); the polynucleotide sequence of human FcγRIIa is shown in SEQ ID NO: 200 (BC020823.1) or SEQ ID NO: 201 (NM_001136219.1); the polynucleotide sequence of human FcγRIIb is shown in SEQ ID NO: 202 (BC146678.1) or SEQ ID NO: 203 (NM_004001.3); the polynucleotide sequence of human FcγRIIIa is shown in SEQ ID NO: 204 (BC033678.1) or SEQ ID NO: 205 (NM_001127593.1); and the polynucleotide sequence of human FcγRIIIb is shown in SEQ ID NO: 206 (BC128562.1). The amino acid sequence of human FcγRI is shown in SEQ ID NO: 207 (NP_000557.1); the amino acid sequence of human FcγRIIa is shown in SEQ ID NO: 208 (AAH20823.1), SEQ ID NO: 209, SEQ ID NO: 210, or SEQ ID NO: 211; the amino acid sequence of human FcγRIIb is shown in SEQ ID NO: 212 (AAI46679.1), SEQ ID NO: 213, or SEQ ID NO: 214; the amino acid sequence of human FcγRIIIa is shown in SEQ ID NO: 215 (AAH33678.1), SEQ ID NO: 216, SEQ ID NO: 217, or SEQ ID NO: 218; and the amino acid sequence of human FcγRIIIb is shown in SEQ ID NO: 219 (AAI28563.1). The amino acid sequence of rhesus macaque FcγRIIa is shown in SEQ ID NO: 220 (FcγRIIa1), SEQ ID NO: 221 (FcγRIIa2), or SEQ ID NO: 222 (FcγRIIa3); the amino acid sequence of rhesus macaque FcγRIIb is shown in SEQ ID NO: 223; and the amino acid sequence of rhesus macaque FcγRIIIa is shown in SEQ ID NO: 224. In one aspect, the invention provides a polypeptide comprising a variant Fc region having enhanced FcγRIIb binding activity, compared to a corresponding reference FcγRIIb-binding polypeptide. In some further aspects, the polypeptide of the invention comprises at least one amino acid modification at at least one position selected from the group consisting of: 231, 232, 233, 234, 235, 236, 237, 238, 239, 264, 266, 267, 268, 271, 295, 298, 325, 326, 327, 328, 330, 331, 332, 334, and 396, according to EU numbering. In some specific embodiments, FcγRIIb has the sequence of rhesus macaque FcγRIIb (SEQ ID NO: 223). In some specific embodiments, FcγRIIb has the sequence of human FcγRIIb (e.g., SEQ ID NO: 212, 213, or 214). In one aspect, the invention provides a polypeptide comprising a variant Fc region having enhanced FcγRIIb binding activity, which comprises at least two amino acid modifications, comprising: (a) an amino acid modification at position 236; and (b) at least one amino acid modification at at least one position selected from the group consisting of: 231, 232, 233, 234, 235, 237, 238, 239, 264, 266, 267, 268, 271, 295, 298, 325, 326, 327, 328, 330, 331, 332, 334, and 396, according to EU numbering. In some specific embodiments, FcγRIIb has the sequence of rhesus macaque FcγRIIb (SEQ ID NO: 223). In some specific embodiments, FcγRIIb has the sequence of human FcγRIIb (e.g., SEQ ID NO: 212, 213, or 214). In one aspect, the invention provides a polypeptide comprising a variant Fc region having enhanced FcγRIIb binding activity, which comprises an amino acid modification at position 236, according to EU numbering. In one aspect, the invention provides a polypeptide comprising a variant Fc region having enhanced FcγRIIb binding activity, which comprises at least two amino acid modifications, including: (a) an amino acid modification at position 236; and (b) at least one amino acid modification at at least one position selected from the group consisting of: 231, 232, 235, 239, 268, 295, 298, 326, 330, and 396, according to EU numbering. In yet another embodiment, the variant Fc region comprises an amino acid modification at at least one position selected from the group consisting of: 231, 232, 235, 239, 268, 295, 298, 326, 330, and 396, according to EU numbering. In yet another embodiment, the variant Fc region comprises an amino acid modification at at least one position selected from the group consisting of: 268, 295, 326, and 330, according to EU numbering. In some specific embodiments, FcγRIIb has the sequence of rhesus FcγRIIb (SEQ ID NO: 223). In some specific embodiments, FcγRIIb has the sequence of human FcγRIIb (e.g., SEQ ID NO: 212, 213, or 214). In another aspect, the invention provides a polypeptide comprising a variant Fc region having enhanced FcγRIIb binding activity, which comprises any one of the following amino acid modifications (1)-(37): (1) positions 231, 236, 239, 268 and 330; (2) positions 231, 236, 239, 268, 295 and 330; (3) positions 231, 236, 268 and 330; (4) positions 231, 236, 268, 295 and 330; (5) positions 232, 236, 239, 268, 295 and 330; (6) positions 232, 236, 268, 295 and 330; (7) positions 232, 236, 268 and 330; (8) positions 235, 236, 268, 295, 326 and 330; (9) positions 235, 236, 268, 295 and 330; (10) positions 235, 236, 268 and 330; (11) positions 235, 236, 268, 330 and 396; (12) positions 235, 236, 268 and 396; (13) positions 236, 239, 268, 295, 298 and 330; (14) positions 236, 239, 268, 295, 326 and 330; (15) positions 236, 239, 268, 295 and 330; (16) positions 236, 239, 268, 298 and 330; (17) positions 236, 239, 268, 326 and 330; (18) positions 236, 239, 268 and 330; (19) positions 236, 239, 268, 330 and 396; (20) positions 236, 239, 268 and 396; (21) positions 236 and 268; (22) positions 236, 268 and 295; (23) positions 236, 268, 295, 298 and 330; (24) positions 236, 268, 295, 326 and 330; (25) positions 236, 268, 295, 326, 330 and 396; (26) positions 236, 268, 295 and 330; (27) positions 236, 268, 295, 330 and 396; (28) positions 236, 268, 298 and 330; (29) positions 236, 268, 298 and 396; (30) positions 236, 268, 326 and 330; (31) positions 236, 268, 326, 330 and 396; (32) positions 236, 268 and 330; (33) positions 236, 268, 330 and 396; (34) positions 236, 268 and 396; (35) positions 236 and 295; (36) positions 236, 330 and 396; and (37) positions 236 and 396, according to EU numbering. In some specific embodiments, FcγRIIb has the sequence of rhesus monkey FcγRIIb (sequence identification number: 223).In some specific embodiments, FcγRIIb has the sequence of human FcγRIIb (e.g., Sequence Identification No.: 212, 213 or 214). In another embodiment, the variant Fc region having enhanced FcγRIIb binding activity comprises at least one amino acid selected from the group consisting of: (a) Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, Trp, Tyr at position 231; (b) Ala, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, Trp, Tyr at position 232; (c) Asp at position 233; (d) Trp, Tyr at position 234; (e) Trp at position 235; (f) Ala, Asp, Glu, His, Ile, Leu, Met, Asn, Gln, Ser, Thr, Val at position 236; (g) Asp, Tyr at position 237; (h) Glu, Ile, Met, Gln, Tyr at position 238; (i) Ile, Leu, Asn, Pro, Val at position 239; (j) Ile at position 264; (k) Phe at position 266; (l) Ala, His, Leu at position 267; (m) Asp, Glu at position 268; (n) Asp, Glu, Gly at position 271; (o) Leu at position 295; (p) Leu at position 298; (q) Glu, Phe, Ile, Leu at position 325; (r) Thr at position 326; (s) Ile, Asn at position 327; (t) Thr at position 328; (u) Lys, Arg at position 330; (v) Glu at position 331; (w) Asp at position 332; (x) Asp, Ile, Met, Val, Tyr at position 334; and (y) Ala, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, Trp, Tyr at position 39, according to EU numbering. In some specific embodiments, FcγRIIb has the sequence of rhesus monkey FcγRIIb (Sequence Identification No.: 223). In some specific embodiments, FcγRIIb has the sequence of human FcγRIIb (e.g., Sequence Identification No.: 212, 213 or 214). In yet another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises at least one amino acid modification (e.g., substitution) selected from the group consisting of (a) Gly, Thr at position 231; (b) Asp at position 232; (c) Trp at position 235; (d) Asn, Thr at position 236; (e) Val at position 239; (f) Asp, Glu at position 268; (g) Leu at position 295; (h) Leu at position 298; (i) Thr at position 326; (j) Lys, Arg at position 330; and (k) Lys, Met at position 396, according to EU numbering. In yet another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises amino acid modifications (e.g., substitutions) of Asn at position 236, Glu at position 268, Lys at position 330 and Met at position 396, according to EU numbering. In yet another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises amino acid modifications (e.g., substitutions) of Asn at position 236, Asp at position 268 and Lys at position 330, according to EU numbering. In yet another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises amino acid modifications (e.g., substitutions) of Asn at position 236, Asp at position 268, Leu at position 295 and Lys at position 330, according to EU numbering. In yet another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises amino acid modifications (e.g., substitutions) of Thr at position 236, Asp at position 268 and Lys at position 330, according to EU numbering. In yet another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises amino acid modifications (e.g., substitutions) of Asn at position 236, Asp at position 268, Leu at position 295, Thr at position 326 and Lys at position 330, according to EU numbering. In yet another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises amino acid modifications (e.g., substitutions) of Trp at position 235, Asn at position 236, Asp at position 268, Leu at position 295, Thr at position 326 and Lys at position 330, according to EU numbering. In one aspect, the invention provides a polypeptide comprising an Fc region having enhanced FcγRIIb binding activity, which comprises an amino acid modification at position 238, according to EU numbering. In one aspect, the invention provides a polypeptide comprising an Fc region having enhanced FcγRIIb binding activity, which comprises at least one amino acid modification at at least one position selected from the group consisting of: 234, 238, 250, 264, 267, 307, and 330, according to EU numbering. In some further embodiments, the polypeptide comprises at least one amino acid modification at at least one position selected from the group consisting of: 234, 250, 264, 267, 307, and 330, according to EU numbering. In some specific embodiments, FcγRIIb has the sequence of rhesus FcγRIIb (SEQ ID NO: 223). In some specific embodiments, FcγRIIb has the sequence of human FcγRIIb (e.g., SEQ ID NO: 212, 213, or 214). In another aspect, the invention provides a polypeptide comprising an Fc region having enhanced FcγRIIb binding activity, which comprises an amino acid modification of any one of (1)-(9) below: (1) positions 234, 238, 250, 307, and 330; (2) positions 234, 238, 250, 264, 307, and 330; (3) positions 234, 238, 250, 264, 267, 307, and 330; (4) positions 234, 238, 250, 267, 307, and 330; (5) positions 238, 250, 264, 307, and 330; (6) positions 238, 250, 264, 267, 307, and 330; (7) positions 238, 250, 267, 307, and 330; (8) positions 238, 250, and 307; and (9) positions 238, 250, 307, and 330, according to EU numbering. In some specific embodiments, FcγRIIb has the sequence of rhesus FcγRIIb (SEQ ID NO: 223). In some specific embodiments, FcγRIIb has the sequence of human FcγRIIb (e.g., SEQ ID NO: 212, 213, or 214). In another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises at least one amino acid modification (e.g., substitution) selected from the group consisting of: (a) Tyr at position 234; (b) Asp at position 238; (c) Val at position 250; (d) Ile at position 264; (e) Ala at position 267; (f) Pro at position 307; and (g) Lys at position 330, according to EU numbering. In another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises an amino acid modification (e.g., substitution) of Asp at position 238, according to EU numbering. In another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises amino acid modifications (e.g., substitutions) of Asp at position 238, Val at position 250, and Pro at position 307, according to EU numbering. In another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises amino acid modifications (e.g., substitutions) of Asp at position 238, Val at position 250, Pro at position 307, and Lys at position 330, according to EU numbering. In another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises amino acid modifications (e.g., substitutions) of Asp at position 238, Val at position 250, Ile at position 264, Pro at position 307, and Lys at position 330, according to EU numbering. In another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises amino acid modifications (e.g., substitutions) of Asp at position 238, Val at position 250, Ala at position 267, Pro at position 307, and Lys at position 330, according to EU numbering. In another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises amino acid modifications (e.g., substitutions) of Tyr at position 234, Asp at position 238, Val at position 250, Pro at position 307, and Lys at position 330, according to EU numbering. In another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises amino acid modifications (e.g., substitutions) of Tyr at position 234, Asp at position 238, Val at position 250, Ala at position 267, Pro at position 307, and Lys at position 330, according to EU numbering. In another embodiment, a variant Fc region having enhanced FcγRIIb binding activity comprises amino acid modifications (e.g., substitutions) of Asp at position 238, Val at position 250, Ile at position 264, Ala at position 267, Pro at position 307, and Lys at position 330, according to EU numbering.In yet another embodiment, variant Fc regions having enhanced FcγRIIb binding activity include amino acid modifications (e.g., substitutions) of Tyr at position 234, Asp at position 238, Val at position 250, Ile at position 264, Pro at position 307, and Lys at position 330, according to EU numbering. In yet another embodiment, variant Fc regions having enhanced FcγRIIb binding activity include amino acid modifications (e.g., substitutions) of Tyr at position 234, Asp at position 238, Val at position 250, Ile at position 264, Ala at position 267, Pro at position 307, and Lys at position 330, according to EU numbering. In some specific embodiments, FcγRIIb has the sequence of rhesus FcγRIIb (SEQ ID NO: 223). In some specific embodiments, FcγRIIb has the sequence of human FcγRIIb (e.g., SEQ ID NO: 212, 213, or 214). In another aspect, the invention provides an isolated polypeptide comprising a variant Fc region having an increased isoelectric point (pI). In some specific embodiments, the variant Fc regions described herein include at least two amino acid modifications in the parental Fc region. In some specific embodiments, each amino acid modification increases the isoelectric point of the variant Fc region relative to the isoelectric point of the parental Fc region. They are based on the finding that antibodies having an increased pI due to modification of at least two amino acid residues can enhance antigen clearance from plasma, e.g., when the antibody is administered in vivo. In the present invention, the pI can be a theoretical or experimentally determined pI. The value of the pI can be determined, for example, by isoelectric focusing well-known to those of ordinary skill in the art. The theoretical pI value can be calculated, for example, using gene and amino acid sequence analysis software (such as Genetyx). In one embodiment, the pI value can be increased, for example, by at least 0.01, 0.03, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5 or more, at least 0.6, 0.7, 0.8, 0.9 or more, at least 1.0, 1.1, 1.2, 1.3, 1.4, 1.5 or more, or at least 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 3.0 or more, compared to before the modification. In some specific embodiments, the amino acids used to increase the pI may be exposed on the surface of the variant Fc region. In the present invention, the amino acids that can be exposed on the surface generally refer to the amino acid residues located on the surface of the polypeptide constituting the variant Fc region. The amino acid residues located on the surface of the polypeptide refer to the amino acid residues whose side chains can contact solvent molecules (which are generally and mostly water molecules). However, the side chains do not necessarily have to be completely in contact with the solvent molecules, and even when a part of the side chain is in contact with the solvent molecules, the amino acid is also defined as an "amino acid residue located on the surface". The amino acid residues located on the surface of the polypeptide also include amino acid residues that are close to the surface and thus can be affected by the charge of amino acid residues whose side chains can contact (even partially) solvent molecules. Those of ordinary skill in the art can prepare a homology model of the polypeptide, for example, using commercially available software. Alternatively, methods well-known to those of ordinary skill in the art, such as X-ray crystallography, may be used. The amino acid residues that can be exposed on the surface can be determined, for example, using the coordinates of a three-dimensional model, which uses a computer program such as the InsightII program (Accelrys). The position of the exposed surface can be determined using algorithms well-known in the art (e.g., Lee and Richards ( J. Mol. Biol. 55:379-400 (1971)); Connolly ( J. Appl. Cryst.16:548-558 (1983)). The position of the exposed surface can be determined using software applicable to protein models and three-dimensional structure information. Software that can be used for such purposes includes, for example, the SYBYL Biopolymer Module software (Tripos Associates). When the algorithm requires the user to input size parameters, the "size" of the probe used for measurement can be set to a radius of about 1.4 angstroms (Å) or less. In addition, a method for determining the region of the exposed surface using personal computer software has been described in Pacios ( Comput. Chem.18(4):377-386 (1994); J. Mol. Model. 1:46-53 (1995)). Based on this information above, suitable amino acid residues located on the surface of the polypeptide constituting the variant Fc region can be selected. In some specific embodiments, the polypeptide includes a variant Fc region and an antigen-binding domain. In still other embodiments, the antigen is a soluble antigen. In one embodiment, the antigen is present in the biological fluids of a subject (e.g., plasma, tissue fluid, lymph fluid, ascites, and pleural fluid). The antigen can also be a membrane antigen. In still other embodiments, the antigen-binding activity of the antigen-binding domain changes according to ionic concentration conditions. In one embodiment, the ionic concentration is not particularly limited and refers to the hydrogen ion concentration (pH) or the metal ion concentration. As used herein, a metal ion refers to an ion of a Group I element other than hydrogen, such as an alkali metal and a copper group element, a Group II element such as an alkaline earth metal and a zinc group element, a Group III element other than boron, a Group IV element other than carbon and silicon, a Group VIII element such as an iron group and a platinum group element, an element belonging to Subgroup A of Groups V, VI, and VII, and a metal element such as antimony, bismuth, and polonium. In the present invention, metal ions include, for example, calcium ions as described in WO 2012 / 073992 and WO 2013 / 125667. In one embodiment, the "ionic concentration conditions" may be conditions that focus on the different biological behaviors of the antigen-binding domain between low ionic concentration and high ionic concentration. In addition, "the antigen-binding activity of the antigen-binding domain changes according to ionic concentration conditions" means that the antigen-binding activity of the antigen-binding domain changes between low ionic concentration and high ionic concentration (for example, the antigen-binding domain is referred to herein as an "ion concentration-dependent antigen-binding domain"). Compared with the low ionic concentration conditions, the antigen-binding activity of the antigen-binding domain may be higher (stronger) or lower (weaker) under high ionic concentration conditions. In one embodiment, an ion concentration-dependent antigen-binding domain (such as a pH-dependent antigen-binding domain or a calcium ion concentration-dependent antigen-binding domain) can be obtained by conventional methods, for example, as described in WO 2009 / 125825, WO 2012 / 073992, and WO 2013 / 046722. In the present invention, the antigen-binding activity of the antigen-binding domain can be higher under high calcium ion concentration conditions than under low calcium ion concentration conditions. The high calcium ion concentration is not particularly limited, but can be a concentration selected from between 100 μM and 10 mM, between 200 μM and 5 mM, between 400 μM and 3 mM, between 200 μM and 2 mM, between 400 μM and 1 mM, or between 500 μM and 2.5 mM, which is preferably close to the plasma (blood) concentration of calcium ions in vivo. At the same time, the low calcium ion concentration is not particularly limited, but can be a concentration selected from between 0.1 μM and 30 μM, between 0.2 μM and 20 μM, between 0.5 μM and 10 μM, between 1 μM and 5 μM, or between 2 μM and 4 μM, which is preferably close to the concentration of calcium ions in early endosomes in vivo. In one embodiment, the ratio of the antibody binding activity under low calcium ion concentration conditions to that under high calcium ion concentration conditions is not particularly limited, but the ratio of the dissociation constant (KD) under low calcium ion concentration conditions to the KD under high calcium ion concentration conditions, that is, KD (low calcium ion concentration conditions) / KD (high calcium ion concentration conditions), is 2 or greater, 10 or greater, or 40 or greater. The upper limit of the ratio can be 400, 1000, or 10000, as long as such an antigen-binding domain can be manufactured by techniques well-known to those of ordinary skill in the art. Alternatively, for example, the dissociation rate constant (kd) can be used instead of KD. In this case, the ratio of kd under low calcium ion concentration conditions to kd under high calcium ion concentration conditions, that is, kd (low calcium ion concentration conditions) / kd (high calcium ion concentration conditions), is 2 or greater, 5 or greater, 10 or greater, or 30 or greater. The upper limit of the ratio can be 50, 100, or 200, as long as the antigen-binding domain can be manufactured based on the common general knowledge of those of ordinary skill in the art. In the present invention, the antigen-binding activity of the antigen-binding domain can be higher under low hydrogen ion concentration (neutral pH) than under high hydrogen ion concentration (acidic pH). The acidic pH can be, for example, a pH selected from pH 4.0 to pH 6.5, selected from pH 4.5 to pH 6.5, selected from pH 5.0 to pH 6.5, or selected from pH 5.5 to pH 6.5, which is preferably close to the in vivo pH of early endosomes. The acidic pH can also be, for example, pH 5.8 or pH 6.0. In some specific embodiments, the acidic pH is pH 5.8. At the same time, the neutral pH can be, for example, a pH selected from pH 6.7 to pH 10.0, selected from pH 6.7 to pH 9.5, selected from pH 7.0 to pH 9.0, or selected from pH 7.0 to pH 8.0, which is preferably close to the in vivo pH in plasma (blood). The neutral pH can also be, for example, pH 7.4 or pH 7.0. In some specific embodiments, the neutral pH is pH 7.4. In one embodiment, the ratio of the antibody binding activity at acidic pH to that at neutral pH is not limited, but the ratio of the dissociation constant (KD) at acidic pH to the KD at neutral pH, i.e., KD(acidic pH) / KD(neutral pH), is 2 or greater, 10 or greater, or 40 or greater. The upper limit of the ratio can be 400, 1000, or 10000, as long as such an antigen-binding domain can be manufactured by techniques well-known to those of ordinary skill in the art. Alternatively, for example, the dissociation rate constant (kd) can be used instead of KD. In this case, the ratio of kd at acidic pH to kd at neutral pH, i.e., kd(acidic pH) / kd(neutral pH), is 2 or greater, 5 or greater, 10 or greater, or 30 or greater. The upper limit of the ratio can be 50, 100, or 200, as long as the antigen-binding domain can be manufactured based on the common general knowledge of those of ordinary skill in the art. In one embodiment, for example, at least one amino acid residue is replaced with an amino acid residue having a side-chain pKa of 4.0 - 8.0, and / or at least one amino acid having a side-chain pKa of 4.0 - 8.0 is inserted into the antibody-binding domain, as described in WO 2009 / 125825. The amino acid can be substituted and / or inserted at any position as long as the antigen-binding activity of the antigen-binding domain becomes weaker at acidic pH than at neutral pH compared to before the substitution or insertion. When the antigen-binding domain has a variable region or CDR, the position can be within the variable region or CDR. The number of amino acids to be substituted or inserted can be appropriately determined by conventional methods; and the number can be one or more. Amino acids having a side-chain pKa of 4.0 - 8.0 can be used to change the antigen-binding activity of the antigen-binding domain according to the hydrogen ion concentration conditions. Such amino acids include, for example, neutral amino acids such as His (H) and Glu (E), and non-neutral amino acids such as histidine analogs (US2009 / 0035836), m-NO2-Tyr (pKa 7.45), 3,5-Br2-Tyr (pKa 7.21), and 3,5-I2-Tyr (pKa 7.38) (Heyl et al., Bioorg. Med. Chem. 11(17):3761 - 3768 (2003)). Amino acids having a side-chain pKa of 6.0 - 7.0 can also be used, which include, for example, His (H). In another embodiment, for a variant Fc region with an increased pI, preferred antigen-binding domains have been described and can be obtained by the methods described in Japanese Patent Application Nos. JP2015 - 021371 and JP2015 - 185254. In some specific embodiments, the variant Fc region having an increased pI includes at least two amino acid modifications at at least two positions selected from the group consisting of: 285, 311, 312, 315, 318, 333, 335, 337, 341, 342, 343, 384, 385, 388, 390, 399, 400, 401, 402, 413, 420, 422, and 431, according to EU numbering. In yet other embodiments, the variant Fc region having an increased pI includes at least two amino acid modifications at at least two positions selected from the group consisting of: 311, 341, 343, 384, 399, 400, 401, 402, and 413, according to EU numbering. In another aspect, the invention provides a polypeptide comprising a variant Fc region having an increased pI, which comprises any of the following amino acid modifications in (1)-(10): (1) positions 311 and 341; (2) positions 311 and 343; (3) positions 311, 343, and 413; (4) positions 311, 384, and 413; (5) positions 311 and 399; (6) positions 311 and 401; (7) positions 311 and 413; (8) positions 400 and 413; (9) positions 401 and 413; and (10) positions 402 and 413, according to EU numbering. A method of increasing the pI of a protein is, for example, to reduce the number of amino acids with negatively charged side chains (e.g., aspartic acid and glutamic acid) and / or increase the number of amino acids with positively charged side chains (e.g., arginine, lysine, and histidine) under neutral pH conditions. Amino acids with negatively charged side chains have a negative charge of -1 under pH conditions that are sufficiently higher than the pKa of their side chains, which is a theory well-known to those of ordinary skill in the art. For example, the theoretical pKa of the side chain of aspartic acid is 3.9, and the side chain has a negative charge of -1 under neutral pH conditions (e.g., in a solution at pH 7.0). Conversely, amino acids with positively charged side chains have a positive charge of +1 under pH conditions that are sufficiently lower than the pKa of their side chains. For example, the theoretical pKa of the side chain of arginine is 12.5, and the side chain has a positive charge of +1 under neutral pH conditions (e.g., in a solution at pH 7.0). At the same time, under neutral pH conditions (e.g., in a solution at pH 7.0), amino acids with uncharged side chains are known to include 15 neutral amino acids, namely, alanine, cysteine, phenylalanine, glycine, isoleucine, leucine, methionine, asparagine, proline, glutamine, serine, threonine, valine, tryptophan, and tyrosine. Of course, it is understood that the amino acids that increase the pI can be non-neutral amino acids. Continuing as described above, methods for increasing the pI of a protein at neutral pH conditions (e.g., in a solution at pH 7.0) can impart a +1 charge change to the protein of interest. For example, by substituting aspartic acid or glutamic acid (which have a -1 negative charge on their side chains) with amino acids having uncharged side chains in the amino acid sequence of the protein. Additionally, a +1 charge change can be imparted to the protein, for example, by substituting amino acids with uncharged side chains with arginine or lysine (which have a +1 positive charge on their side chains). Furthermore, a +2 charge change can be imparted to the protein simultaneously by substituting aspartic acid or glutamic acid (which have a -1 negative charge on their side chains) with arginine or lysine (which have a +1 positive charge on their side chains). Alternatively, to increase the pI of a protein, amino acids with uncharged side chains and / or preferably amino acids with positively charged side chains can be added or inserted into the amino acid sequence of the protein, or amino acids with uncharged side chains and / or preferably amino acids with negatively charged side chains can be deleted from the amino acid sequence of the protein. It is understood that, for example, in addition to the charges derived from their side chains, the N-terminal and C-terminal amino acid residues of a protein have charges derived from the main chain (the NH of the amino group at the N-terminal 3 + and the COO of the carboxyl group at the C-terminal - ). Thus, the pI of a protein can also be increased by performing some additions, deletions, substitutions, or insertions on the main chain-derived functional groups. Amino acid substitutions for increasing the pI include, for example, substituting amino acids with negatively charged side chains with amino acids having uncharged side chains, substituting amino acids with uncharged side chains with amino acids having positively charged side chains, and substituting amino acids with negatively charged side chains with amino acids having positively charged side chains in the amino acid sequence of the parental Fc region, which can be performed alone or in appropriate combinations. Amino acid insertions or additions for increasing the pI include, for example, inserting or adding amino acids with uncharged side chains and / or inserting or adding amino acids with positively charged side chains into the amino acid sequence of the parental Fc region, which can be performed alone or in appropriate combinations. Amino acid deletions for increasing the pI include, for example, deleting amino acids with uncharged side chains and / or deleting amino acids with negatively charged side chains from the amino acid sequence of the parental Fc region, which can be performed alone or in appropriate combinations. In one embodiment, the natural amino acids for increasing pI can be classified as follows: (a) Amino acids with negatively charged side chains can be Glu (E) or Asp (D); (b) Amino acids with uncharged side chains can be Ala (A), Asn (N), Cys (C), Gln (Q), Gly (G), His (H), Ile (I), Leu (L), Met (M), Phe (F), Pro (P), Ser (S), Thr (T), Trp (W), Tyr (Y) or Val (V); and (c) Amino acids with positively charged side chains can be His (H), Lys (K) or Arg (R). In one embodiment, the modified amino acid is inserted or substituted with Lys (K) or Arg (R). In another aspect, the invention provides an isolated polypeptide comprising a variant Fc region having enhanced FcγRIIb binding activity and increased pI. In some specific embodiments, the variant Fc region described herein comprises at least two amino acid modifications in the parental Fc region. In one aspect, the invention provides a polypeptide comprising a variant Fc region having enhanced FcγRIIb binding activity and increased pI, which comprises at least three amino acid modifications, including: (a) at least one amino acid modification at at least one position selected from the group consisting of: 231, 232, 233, 234, 235, 236, 237, 238, 239, 264, 266, 267, 268, 271, 295, 298, 325, 326, 327, 328, 330, 331, 332, 334 and 396, according to EU numbering; and (b) at least two amino acid modifications at at least two positions selected from the group consisting of: 285, 311, 312, 315, 318, 333, 335, 337, 341, 342, 343, 384, 385, 388, 390, 399, 400, 401, 402, 413, 420, 422 and 431, according to EU numbering. In one aspect, the invention provides a polypeptide comprising a variant Fc region having enhanced FcγRIIb binding activity and increased pI, and which comprises at least three amino acid modifications, including: (a) at least one amino acid modification at at least one position selected from the group consisting of: 231, 232, 235, 236, 239, 268, 295, 298, 326, 330 and 396, according to EU numbering; and (b) at least two amino acid modifications at at least two positions selected from the group consisting of: 311, 341, 343, 384, 399, 400, 401, 402 and 413, according to EU numbering. In another aspect, the invention provides a polypeptide comprising a variant Fc region having enhanced FcγRIIb binding activity and an increased pI, which comprises any one of the following amino acid modifications (1)-(9): (1) positions 235, 236, 268, 295, 311, 326, 330 and 343; (2) positions 236, 268, 295, 311, 326, 330 and 343; (3) positions 236, 268, 295, 311, 330 and 413; (4) positions 236, 268, 311, 330, 396 and 399; (5) positions 236, 268, 311, 330 and 343; (6) positions 236, 268, 311, 330, 343 and 413; (7) positions 236, 268, 311, 330, 384 and 413; (8) positions 236, 268, 311, 330 and 413; and (9) positions 236, 268, 330, 396, 400 and 413, according to EU numbering. In some specific embodiments, FcγRIIb has the sequence of rhesus FcγRIIb (SEQ ID NO: 223). In some specific embodiments, FcγRIIb has the sequence of human FcγRIIb (e.g., SEQ ID NO: 212, 213 or 214). In one aspect, the invention provides a polypeptide comprising a variant Fc region having enhanced FcγRIIb binding activity and an increased pI, which comprises at least three amino acid modifications, including: (a) at least one amino acid modification at at least one position selected from the group consisting of: 234, 238, 250, 264, 267, 307 and 330, according to EU numbering; and (b) at least two amino acid modifications at at least two positions selected from the group consisting of: 285, 311, 312, 315, 318, 333, 335, 337, 341, 342, 343, 384, 385, 388, 390, 399, 400, 401, 402, 413, 420, 422 and 431, according to EU numbering. In still other embodiments, the polypeptide comprises at least two amino acid modifications at at least two positions selected from the group consisting of: 311, 341, 343, 384, 399, 400, 401, 402 and 413, according to EU numbering. In some specific embodiments, FcγRIIb has the sequence of rhesus FcγRIIb (SEQ ID NO: 223). In some specific embodiments, FcγRIIb has the sequence of human FcγRIIb (e.g., SEQ ID NO: 212, 213 or 214). In another aspect, the invention provides a polypeptide comprising a variant Fc region having enhanced FcγRIIb binding activity and an increased pI, which comprises an amino acid modification of any one of the following (1)-(16): (1) positions 234, 238, 250, 264, 307, 311, 330 and 343; (2) positions 234, 238, 250, 264, 307, 311, 330 and 413; (3) positions 234, 238, 250, 264, 267, 307, 311, 330 and 343; (4) positions 234, 238, 250, 264, 267, 307, 311, 330 and 413; (5) positions 234, 238, 250, 267, 307, 311, 330 and 343; (6) positions 234, 238, 250, 267, 307, 311, 330 and 413; (7) positions 234, 238, 250, 307, 311, 330 and 343; (8) positions 234, 238, 250, 307, 311, 330 and 413; (9) positions 238, 250, 264, 267, 307, 311, 330 and 343; (10) positions 238, 250, 264, 267, 307, 311, 330 and 413; (11) positions 238, 250, 264, 307, 311, 330 and 343; (12) positions 238, 250, 264, 307, 311, 330 and 413; (13) positions 238, 250, 267, 307, 311, 330 and 343; (14) positions 238, 250, 267, 307, 311, 330 and 413; (15) positions 238, 250, 307, 311, 330 and 343; and (16) positions 238, 250, 307, 311, 330 and 413, according to EU numbering. In yet another embodiment, the variant Fc region comprises an amino acid modification selected from any one of a single modification, a combination of single modifications, or a combination of modifications as described in Tables 14-30. In some embodiments, the polypeptide comprises the variant Fc region of the invention. In yet another embodiment, the polypeptide is a constant region of an antibody heavy chain. In yet another embodiment, the polypeptide is an antibody heavy chain. In yet another embodiment, the polypeptide is an antibody. In yet another embodiment, the polypeptide is an Fc fusion protein. In yet another embodiment, the invention provides a polypeptide comprising an amino acid sequence of any one of SEQ ID NOs: 229-381. As used herein, "parent Fc region" refers to the Fc region prior to introduction of the amino acid modifications described herein. Examples of preferred parent Fc regions include Fc regions derived from natural antibodies. Antibodies include, for example, IgA (IgA1, IgA2), IgD, IgE, IgG (IgG1, IgG2, IgG3, IgG4), and IgM, etc. Antibodies can be derived from humans or monkeys (e.g., rhesus monkey, cynomolgus monkey, marmoset, chimpanzee, or baboon). Natural antibodies can also include naturally occurring mutations. Many allelic sequences of IgG due to gene polymorphism have been described in "Sequences of Proteins of Immunological Interest", NIH Publication No. 91-3242, and any of them can be used in the present invention. In particular, for human IgG1, the amino acid sequence at positions 356 to 358 (EU numbering) can be DEL or EEM. Preferred examples of the parent Fc region include Fc regions derived from the heavy chain constant regions of human IgG1 (SEQ ID NO: 195), human IgG2 (SEQ ID NO: 196), human IgG3 (SEQ ID NO: 197), and human IgG4 (SEQ ID NO: 198). Another preferred example of the parent Fc region is the Fc region derived from the heavy chain constant region SG1 (SEQ ID NO: 9). In addition, the parent Fc region can be an Fc region produced by adding amino acid modifications other than those described herein to an Fc region derived from a natural antibody. In addition, amino acid modifications performed for other purposes can be incorporated into the variant Fc regions described herein. For example, amino acid substitutions that improve FcRn binding activity can be added (Hinton et al., J. Immunol. 176(1):346-356 (2006); Dall'Acqua et al., J. Biol. Chem. 281(33):23514-23524 (2006); Petkova et al., Intl. Immunol. 18(12):1759-1769 (2006); Zalevsky et al., Nat. Biotechnol. 28(2):157-159 (2010); WO 2006 / 019447; WO 2006 / 053301; and WO 2009 / 086320), as well as amino acid substitutions for improving antibody heterogeneity or stability (WO 2009 / 041613). Alternatively, polypeptides having enhanced antigen clearance properties described in WO 2011 / 122011, WO 2012 / 132067, WO 2013 / 046704, or WO 2013 / 180201, polypeptides having specific binding to target tissues described in WO 2013 / 180200, polypeptides having repetitive binding to multiple antigen molecules described in WO 2009 / 125825, WO 2012 / 073992, or WO 2013 / 047752, can be combined with the variant Fc region described herein. Alternatively, for the purpose of conferring other antigen-binding capabilities, the amino acid modifications disclosed in EP1752471 and EP1772465 can be combined into the CH3 of the variant Fc region described herein. Alternatively, for the purpose of increasing plasma retention, amino acid modifications that lower the pI of the constant region (WO 2012 / 016227) can be combined into the variant Fc region described herein. Alternatively, for the purpose of enhancing cell uptake, amino acid modifications that increase the pI of the constant region (WO 2014 / 145159) can be combined into the variant Fc region described herein. Alternatively, for the purpose of enhancing the elimination of target molecules from plasma, amino acid modifications that increase the pI of the constant region (Japanese Patent Application Nos. JP2015-021371 and JP2015-185254) can be combined into the variant Fc region described herein. In one embodiment, such modifications can include, for example, substitutions at at least one position selected from the group consisting of 311, 343, 384, 399, 400, and 413, according to EU numbering. In yet another embodiment, such substitutions can be the replacement of the amino acid with Lys or Arg at each position. Amino acid modifications that enhance human FcRn binding activity at acidic pH can also be combined into the variant Fc region described herein. Specifically, such modifications can include, for example, replacing Met at position 428 with Leu and Asn at position 434 with Ser, according to EU numbering (Zalevsky et al., Nat. Biotechnol. 28:157-159 (2010)); replacing Asn at position 434 with Ala (Deng et al., Metab. Dispos. 38(4):600-605 (2010)); substitution of Tyr for Met at position 252, Thr for Ser at position 254, and Glu for Thr at position 256 (Dall'Acqua et al., J. Biol. Chem. 281:23514-23524 (2006)); substitution of Thr at position 250 with Gln and substitution of Met at position 428 with Leu (Hinton et al., J. Immunol. 176(1):346-356 (2006)); replacing Asn at position 434 with His (Zheng et al., Clin. Pharmacol. Ther. 89(2):283-290 (2011), and modifications as described in WO 2010 / 106180, WO 2010 / 045193, WO 2009 / 058492, WO 2008 / 022152, WO 2006 / 050166, WO 2006 / 053301, WO 2006 / 031370, WO 2005 / 123780, WO 2005 / 047327, WO 2005 / 037867, WO 2004 / 035752 or WO 2002 / 060919. Such modifications may include, for example, at least one selected from the group consisting of: substitution of Met at position 428 with Leu, substitution of Asn at position 434 with Ala, and substitution of Tyr at position 436 with Thr. Those modifications may further include substitution of Gln at position 438 with Arg and / or substitution of Ser at position 440 with Glu (Japanese Patent Application Nos. JP2015-021371 and JP2015-185254). Two or more polypeptides comprising the variant Fc regions described herein can be included in one molecule, wherein the two polypeptides comprising the variant Fc regions are associated, much like antibodies. The type of antibody is not limited, and IgA (IgA1, IgA2), IgD, IgE, IgG (IgG1, IgG2, IgG3, IgG4) and IgM can be used. Two associated polypeptides comprising a variant Fc region may be polypeptides comprising a variant Fc region into which the same amino acid modification has been introduced (hereinafter referred to as a homologous variant Fc region), or polypeptides comprising a variant Fc region into which different amino acid modifications have been introduced, or polypeptides comprising a variant Fc region in which an amino acid modification has been introduced into only one of the Fc regions (hereinafter referred to as a heterologous polypeptide comprising a variant Fc region). One of the preferred amino acid modifications is a modification in the loop structure from position 233 to 239 (EU numbering) in the CH2 domain of the Fc region, which is involved in the binding to FcγRIIb and FcγRIIa. Preferably, the modification is introduced into the loop structure of the CH2 domain of one of the Fc regions that enhances the FcγRIIb binding activity and / or selectivity, while the other modification is introduced into the loop structure of the CH2 domain of the other Fc region that destabilizes it. Examples of amino acid modifications that can destabilize the loop structure of the CH2 domain can be substituting at least one amino acid selected from the amino acids at positions 235, 236, 237, 238 and 239 with other amino acids. Specifically, destabilization can be achieved, for example, by modifying the amino acid at position 235 to Asp, Gln, Glu or Thr, the amino acid at position 236 to Asn, the amino acid at position 237 to Phe or Trp, the amino acid at position 238 to Glu, Gly or Asn, and the amino acid at position 239 to Asp or Glu, according to EU numbering. Regarding the binding of heterologous polypeptides comprising a variant Fc region, techniques for suppressing the unintended binding of homologous polypeptides comprising a variant Fc region can be employed by introducing an electrostatic repulsion at the interface of the CH2 or CH3 domain of the Fc region, as described in WO 2006 / 106905. For example, the amino acid residues in contact with the interface of the CH2 or CH3 domain of the Fc region include the residue at position 356 (EU numbering) in the CH3 domain, the residue at position 439 (EU numbering), the residue at position 357 (EU numbering), the residue at position 370 (EU numbering), the residue at position 399 (EU numbering), and the residue at position 409 (EU numbering). More specifically, for example, an Fc region can be produced in which one to three pairs of amino acid residues having the same charge are selected from the following (1) to (3): (1) the amino acid residues at positions 356 and 439 in the CH3 domain (EU numbering); (2) the amino acid residues at positions 357 and 370 in the CH3 domain (EU numbering); and (3) the amino acid residues at positions 399 and 409 in the CH3 domain (EU numbering). In addition, heterologous polypeptides comprising variant Fc regions can be produced, wherein one to three pairs of amino acid residues selected from the above (1) to (3) have the same charge in the CH3 domain of the first Fc region, and the pair of amino acid residues selected from the aforementioned first Fc region also have the same charge in the CH3 domain of the second Fc region, but the charges in the first and second Fc regions are opposite. In the above Fc region, for example, negatively charged amino acid residues are preferably selected from glutamic acid (E) and aspartic acid (D), while positively charged amino acid residues are preferably selected from lysine (K), arginine (R), and histidine (H). Other known techniques can additionally be used for the binding of heterologous polypeptides comprising variant Fc regions. Specifically, such a technique is by replacing the amino acid side chain present in one of the Fc regions with a larger side chain (knob; which represents a "bump"), and replacing the amino acid side chain present in the Fc region with a smaller side chain (hole; which represents a cavity), to place the knob inside the hole. This can enhance the effective binding between Fc region-containing polypeptides having different amino acid sequences (WO 1996 / 027011; Ridgway et al., Prot. Eng. 9:617-621 (1996); Merchant et al., Nat. Biotech. 16, 677-681 (1998)). In addition, other known techniques can also be used for the heterologous binding of polypeptides comprising variant Fc regions. Strand-exchange engineered domain CH3 heterodimers (Davis et al., Prot. Eng. Des. & Sel., 23:195-202 (2010)) can be effectively used to induce the binding of polypeptides comprising Fc regions. This technique can also be used to effectively induce the binding between polypeptides comprising variant Fc regions having different amino acid sequences. In addition, heterodimeric antibody production techniques using the binding of antibody CH1 and CL and the binding of VH and VL as described in WO 2011 / 028952 can also be used. As described in WO 2008 / 119353 and WO 2011 / 131746, techniques for producing heterodimeric antibodies by pre-producing two homodimeric antibodies, culturing the antibodies under reducing conditions to separate them, and then re-binding them are also possible. As in Strop ( The method described in J. Mol. Biol. 420:204-219 (2012)), which uses a technique for producing heterodimeric antibodies by introducing electrostatic repulsion into the CH3 domain by introducing charged residues such as Lys, Arg, Glu, and Asp, is also possible. In addition, the method described in WO 2012 / 058768, which uses a technique for producing heterodimeric antibodies by adding modifications to the CH2 and CH3 domains, is also possible. When two polypeptides including variant Fc regions having different amino acid sequences are co-expressed, in order to produce a polypeptide including a heterologous variant Fc region, a polypeptide including a homologous variant Fc region is usually also produced as an impurity. In this case, the polypeptide including the heterologous variant Fc region can be effectively obtained by separating and purifying them from the polypeptide including the homologous variant Fc region using conventional techniques. Methods for effectively separating and purifying heterodimeric antibodies from homodimeric antibodies by introducing amino acid modifications into the variable regions of the heavy chains of two antibodies to create an isoelectric point difference between the homodimeric antibody and the heterodimeric antibody have been reported (WO 2007 / 114325). Another method for purifying heterodimeric antibodies using Protein A chromatography has been reported, by constructing a heterodimeric antibody including two heavy chains derived from mouse IgG2a that binds to Protein A and rat IgG2b that does not bind to Protein A (WO 1998 / 050431 and WO 1995 / 033844). In addition, Protein A chromatography can be used to replace the amino acid residues at positions 435 and 436 (EU numbering), which are the Protein A binding positions of the antibody heavy chain, with amino acids such as Tyr or His to generate different Protein A binding affinities, thereby effectively purifying heterodimeric antibodies. In the present invention, amino acid modification refers to any one or a combination of substitution, deletion, addition, insertion, and modification, or the like. In the present invention, amino acid modification can be rewritten as amino acid mutation. When substituting amino acid residues, substitution of different amino acid residues can be carried out with the aim of changing aspects as described in the following (a)-(c): (a) the polypeptide backbone structure in a sheet structure or a helical structure region; (b) the charge or hydrophobicity at the target position; or (c) the size of the side chain. Amino acid residues are classified into the following groups according to their general side-chain properties: (a) hydrophobic: norleucine, Met, Ala, Val, Leu, and Ile; (b) neutral hydrophilic: Cys, Ser, Thr, Asn, and Gln; (c) acidic: Asp and Glu; (d) basic: His, Lys, and Arg; (e) residues that affect chain orientation: Gly and Pro; and (f) aromatic: Trp, Tyr, and Phe. Amino acid modifications are generated by various methods well-known to those of ordinary skill in the art. Such methods include site-directed mutagenesis methods (Hashimoto-Gotoh et al., Gene152:271-275 (1995); Zoller, Meth. Enzymol.100:468-500 (1983); Kramer et al., Nucleic Acids Res.12: 9441-9456 (1984)); Kramer and Fritz, Methods Enzymol.154: 350-367 (1987); and Kunkel, Proc. Natl. Acad. Sci.USA 82:488-492 (1985)), PCR mutagenesis methods, and cassette mutagenesis methods, but are not limited thereto. The number of amino acid modifications introduced into the Fc region is not limited. In some specific embodiments, it can be 1, 2 or less, 3 or less, 4 or less, 5 or less, 6 or less, 8 or less, 10 or less, 12 or less, 14 or less, 16 or less, 18 or less, or 20 or less. Amino acid modifications include post-translational modifications. Specific post-translational modifications can be the addition or deletion of sugar chains. For example, the amino acid residue at position 297 (EU numbering) in the IgG1 constant region can be glycosylated. The modified sugar chain structure is not limited. For example, sialic acid can be added to the sugar chain of the Fc region (MAbs 2010 Sep-Oct, 2(5): 519-527). Generally, antibodies expressed in eukaryotic cells include glycosylation in the constant region. For example, it is known that some types of sugar chains are usually added to antibodies expressed in cells such as natural antibody-producing cells of mammals or eukaryotic cells transformed with an expression vector including DNA encoding the antibody. The eukaryotic cells shown in the text include yeast and animal cells. For example, CHO cells and HEK293 cells are representative animal cells, which are used for transformation with expression vectors including DNA encoding antibodies. On the other hand, a constant region without glycosylation is also included in the present invention. Antibodies with an unglycosylated constant region can be obtained by expressing a gene encoding an antibody in prokaryotic cells such as Escherichia coli. In addition, polypeptides including the variant Fc region of the present invention can be chemically modified with various molecules, such as polyethylene glycol (PEG) and cytotoxic substances. Methods for such chemical modification of polypeptides have been established in the art. In one aspect, the invention provides an isolated polypeptide, which includes a variant Fc region having enhanced FcγRIIb binding activity. In some aspects, the polypeptide is an antibody. In some aspects, the polypeptide is an Fc fusion protein. In some specific embodiments, the antibody is a chimeric antibody or a humanized antibody. The source of the antibody is not particularly limited, but includes, for example, human antibodies, mouse antibodies, rat antibodies, and rabbit antibodies. In some aspects, the polypeptide is an Fc fusion protein. The variable regions of antibodies including the variant Fc region provided herein and the protein binding motif of Fc fusion proteins including the variant Fc region can recognize any antigen. Examples of antigens that can be bound by such antibodies and fusion proteins include, but are not limited to, ligands (cytokines, chemokines, etc.), receptors, cancer antigens, MHC antigens, differentiation antigens, immunoglobulins, and immune complexes partially including immunoglobulins. Examples of cytokines that can be bound by antibodies or fusion proteins including the variant Fc region of the invention and / or recombinantly fused with polypeptides including the disclosed variant Fc region include, but are not limited to, interleukin 1 to 18, colony stimulating factors (G-CSF, M-CSF, GM-CSF, etc.), interferons (IFN-α, IFN-β, IFN-γ, etc.), growth factors (EGF, FGF, IGF, NGF, PDGF, TGF, HGF, etc.), tumor necrosis factors (TNF-α and TNF-β), lymphotoxins, erythropoietin, receptor ligand, SCF, TPO, MCAF, and BMP. Examples of chemokines that can be bound by antibodies or fusion proteins including the variant Fc region of the invention and / or recombinantly fused with polypeptides including the disclosed variant Fc region include, but are not limited to, CC chemokines such as CCL1 to CCL28, CXC chemokines such as CXCL1 to CXCL17, C chemokines such as XCL1 to XCL2, and CX3C chemokines such as CX3CL1. Examples of receptors that can bind to variant Fc regions that may be included in the invention and / or antibodies or fusion proteins recombinantly fused to polypeptides comprising the disclosed variant Fc regions include, but are not limited to, receptors belonging to receptor families such as, for example, the hematopoietic growth factor receptor family, the cytokine receptor family, the tyrosine kinase-type receptor family, the serine / threonine kinase-type receptor family, the TNF receptor family, the G protein-coupled receptor family, the GPI-anchored receptor family, the tyrosine phosphatase-type receptor family, the adhesion factor family, and the hormone receptor family. Receptors belonging to these receptor families and their properties have been described in many publications, such as, for example, Cooke, editor, New Comprehesive Biochemistry Vol.18B "Hormones and their Actions Part II" pp.1-46 (1988) Elsevier Science Publishers BV; Patthy ( Cell61(1):13-14 (1990)); Ullrich ( Cell61(2):203-212 (1990)); Massagué ( Cell69(6):1067-1070 (1992)); Miyajima et al. ( Annu. Rev. Immunol.10:295-331 (1992)); Taga et al. ( FASEB J.6:3387-3396 (1992)); Fantl et al. ( Annu. Rev. Biochem.62:453-481 (1993)); Smith et al. ( Cell76(6):959-962 (1994)); and Flower ( Biochim. Biophys. Acta1422(3): 207-234 (1999)). Examples of specific receptors belonging to the above receptor families include the human or murine erythropoietin (EPO) receptor (Jones et al., Blood76(1):31-35 (1990); D’Andrea et al., Cell57(2):277-285 (1989)), the human or murine granulocyte colony-stimulating factor (G-CSF) receptor (Fukunaga et al., Proc. Natl. Acad. Sci. USA 87(22):8702-8706 (1990), mG-CSFR; Fukunaga et al., Cell 61(2): 341-350 (1990)), human or murine thrombopoietin (TPO) receptor (Vigon et al., Proc. Natl. Acad. Sci. USA. 89(12):5640-5644(1992); Skoda et al., EMBO J. 12(7):2645-2653 (1993)), human or murine insulin receptor (Ullrich et al., Nature 313(6005):756-761 (1985)), human or murine Flt-3 ligand receptor (Small et al., Proc. Natl. Acad. Sci. USA. 91(2):459-463 (1994)), human or murine platelet-derived growth factor (PDGF) receptor (Gronwald et al., Proc. Natl. Acad. Sci. USA. 85(10):3435-3439 (1988)), human or murine interferon (IFN)-α and β receptor (Uze et al., Cell 60(2): 225-234 (1990); Novick et al., Cell 77(3):391-400 (1994)), human or murine leptin receptor, human or murine growth hormone (GH) receptor, human or murine interleukin (IL)-10 receptor, human or murine insulin-like growth factor (IGF)-I receptor, human or murine leukemia inhibitory factor (LIF) receptor, and human or murine ciliary neurotrophic factor (CNTF) receptor. Cancer antigens are antigens that cause the expressing cells to become malignant, and they are also called tumor-specific antigens. When cells become cancerous, abnormal sugar chains that appear on the cell surface or protein molecules are also cancer antigens, and they are also called carbohydrate cancer antigens. Examples of cancer antigens that can be bound by the antibodies or fusion proteins containing the variant Fc region of the invention include, but are not limited to, GPC3, which is a receptor belonging to the above-mentioned GPI-anchored receptor family and is also expressed in many cancers, including liver cancer (Midorikawa et al., Int. J. Cancer 103(4):455-465 (2003)), and EpCAM, which is expressed in many cancers, including lung cancer (Linnenbach et al., Proc. Natl. Acad. Sci. USA 86(1):27-31 (1989)), CA19-9, CA15-3, and sialyl SSEA-1 (SLX). MHC antigens are roughly classified into MHC class I antigens and MHC class II antigens. MHC class I antigens include HLA-A, -B, -C, -E, -F, -G, and -H, while MHC class II antigens include HLA-DR, -DQ, and -DP. Examples of differentiation antigens that can be bound by antibodies or fusion proteins comprising the variant Fc region of the invention and / or recombinantly fused to a polypeptide comprising the disclosed variant Fc region include, but are not limited to, CD1, CD2, CD4, CD5, CD6, CD7, CD8, CD10, CD11a, CD11b, CD11c, CD13, CD14, CD15s, CD16, CD18, CD19, CD20, CD21, CD23, CD25, CD28, CD29, CD30, CD32, CD33, CD34, CD35, CD38, CD40, CD41a, CD41b, CD42a, CD42b, CD43, CD44, CD45, CD45RO, CD48, CD49a, CD49b, CD49c, CD49d, CD49e, CD49f, CD51, CD54, CD55, CD56, CD57, CD58, CD61, CD62E, CD62L, CD62P, CD64, CD69, CD71, CD73, CD95, CD102, CD106, CD122, CD126, and CDw130. Immunoglobulins include IgA, IgM, IgD, IgG, and IgE. Immunocomplexes comprise components of at least any one of the immunoglobulins. Other examples of antigens that can bind to the variant Fc region of the invention and / or antibodies or fusion proteins recombinantly fused to a polypeptide comprising the disclosed variant Fc region include, but are not limited to, 17-IA, 4-1BB, 4Dc, 6-keto-PGF1a, 8-iso-PGF2a, 8-oxo-dG, A1 adenosine receptor, A33, ACE, ACE-2, activin, activin A, activin AB, activin B, activin C, activin RIA, activin RIA ALK-2, activin RIB ALK-4, activin RIIA, activin RIIB, ADAM, ADAM10, ADAM12, ADAM15, ADAM17 / TACE, ADAM8, ADAM9, ADAMTS, ADAMTS4, ADAMTS5, addressin, aFGF, ALCAM, ALK, ALK-1, ALK-7, α-1-antitrypsin, α-V / β-1 antagonist, ANG, Ang, APAF-1, APE, APJ, APP, APRIL, AR, ARC, ART, artemin, anti-Id, ASPARTIC, atrial natriuretic factor, av / b3 integrin, Axl, b2M, B7-1, B7-2, B7-H, B-lymphocyte stimulator (BlyS), BACE, BACE-1, Bad, BAFF, BAFF-R, Bag-1, BAK, Bax, BCA-1, BCAM, Bcl, BCMA, BDNF, b-ECGF, bFGF, BID, Bik, BIM, BLC, BL-CAM, BLK, BMP, BMP-2 BMP-2a, BMP-3 Osteogenin, BMP-4, BMP-2b, BMP-5, BMP-6 Vgr-1, BMP-7 (OP-1), BMP-8 (BMP-8a, OP-2), BMPR, BMPR-IA (ALK-3), BMPR-IB (ALK-6), BRK-2, RPK-1, BMPR-II (BRK-3), BMP, b-NGF, BOK, bombesin, bone-derived neurotrophic factor, BPDE, BPDE-DNA, BTC, complement factor 3(C3), C3a, C4, C5, C5a, C10, CA125, CAD-8, Calcitonin, cAMP, Carcinoembryonic Antigen (CEA), Cancer-Associated Antigen, Cytolysin A, Cytolysin B, Cytolysin C / DPPI, Cytolysin D, Cytolysin E, Cytolysin H, Cytolysin L, Cytolysin O, Cytolysin S, Cytolysin V, Cytolysin X / Z / P, CBL, CCI, CCK2, CCL, CCL1, CCL11, CCL12, CCL13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL2, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9 / 10, CCR, CCR1, CCR10, CCR11, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CD1, CD2, CD3, CD3E, CD4, CD5, CD6, CD7, CD8, CD10, CD11a, CD11b, CD11c, CD13, CD14, CD15, CD16, CD18, CD19, CD20, CD21, CD22, CD23, CD25, CD27L, CD28, CD29, CD30, CD30L, CD32, CD33 (p67 protein), CD34, CD38, CD40, CD40L, CD44, CD45, CD46, CD49a, CD52, CD54, CD55, CD56, CD61, CD64, CD66e, CD74, CD80 (B7-1), CD89, CD95, CD123, CD137, CD138, CD140a, CD146, CD147, CD148, CD152, CD164, CEACAM5, CFTR, cGMP, CINC, Botulinum Toxin, Clostridium Perfringens Toxin, CKb8-1, CLC, CMV, CMVUL, CNTF, CNTN-1, COX, C-Ret, CRG-2, CT-1, CTACK, CTGF, CTLA-4, CX3CL1, CX3CR1, CXCL, CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CXCL15, CXCL16, CXCR, CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, Cytokeratin tumor-associated antigen, DAN, DCC, DcR3, DC-SIGN, Complement regulatory factor (decay-accelerating factor), des(1-3)-IGF-I (brain IGF-1), Dhh, digoxin, DNAM-1, Dnase, Dpp, DPPIV / CD26, Dtk, ECAD, EDA, EDA-A1, EDA-A2, EDAR, EGF, EGFR (ErbB-1), EMA, EMMPRIN, ENA, Endothelin receptor, Enkephalinase, eNOS, Eot, eotaxin 1, EpCAM, ephrin B2 / EphB4, EPO, ERCC, E-selectin, ET-1, Factor IIa, Factor VII, Factor VIIIc, Factor IX, Fibroblast activation protein (FAP), Fas, FcR1, FEN-1, Ferritin, FGF, FGF-19, FGF-2, FGF3, FGF-8, FGFR, FGFR-3, Fibrin, FL, FLIP, Flt-3, Flt-4, Follicle-stimulating hormone, fractalkine, FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, FZD10, G250, Gas6, GCP-2, GCSF, GD2, GD3, GDF, GDF-1, GDF-3 (Vgr-2), GDF-5 (BMP-14, CDMP-1), GDF-6 (BMP-13, CDMP-2), GDF-7 (BMP-12, CDMP-3), GDF8 (Myostatin), GDF-9, GDF-15 (MIC-1), GDNF, GFAP, GFRa-1, GFR-α1, GFR-α2, GFR-α3, GITR, Glucagon, Glut4, Glycoprotein IIb / IIIa (GPIIb / IIIa), GM-CSF, gp130, gp72, GRO, Growth hormone-releasing hormone, Hapten (NP-cap or NIP-cap), HB-EGF, HCC, HCMV gB envelope glycoprotein, HCMVgH envelope glycoprotein, HCMV UL, hematopoietic growth factor (HGF), Hep B gp120, heparanase, Her2, Her2 / neu (ErbB-2), Her3 (ErbB-3), Her4 (ErbB-4), herpes simplex virus (HSV), gB glycoprotein, HSV gD glycoprotein, HGFA, high molecular weight melanoma-associated antigen (HMW-MAA), HIV gp120, HIV IIIB gp 120 V3 loop, HLA, HLA-DR, HM1.24, HMFG PEM, HRG, Hrk, human cardiac myosin, human cytomegalovirus (HCMV), human growth hormone (HGH), HVEM, I-309, IAP, ICAM, ICAM-1, ICAM-3, ICE, ICOS, IFNg, Ig, IgA receptor, IgE, IGF, IGF-binding protein, IGF-1R, IGFBP, IGF-I, IGF-II, IL, IL-1, IL-1R, IL-2, IL-2R, IL-4, IL-4R, IL-5, IL-5R, IL-6, IL-6R, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-18, IL-18R, IL-23, interferon (IFN)-α, IFN-β, IFN-γ, inhibin, iNOS, insulin A chain, insulin B chain, insulin-like growth factor 1, integrin α2, integrin α3, integrin α4, integrin α4 / β1, integrin α4 / β7, integrin α5 (αV), integrin α5 / β1, integrin α5 / β3, integrin α6, integrin β1, integrin β2, interferon γ, IP-10, I-TAC, JE, kallikrein 2, kallikrein 5, kallikrein 6, kallikrein 11, kallikrein 12, kallikrein 14, kallikrein 15, kallikrein L1, kallikrein L2, kallikrein L3, kallikrein L4, KC, KDR, keratinocyte growth factor (KGF), laminin 5, LAMP, LAP, LAP (TGF-1), latent TGF-1, latent TGF-1bp1, LBP, LDGF, LECT2, lefty, Lewis-Y antigen, Lewis-Y related antigen, LFA-1, LFA-3, Lfo, LIF, LIGHT, lipoprotein, LIX, LKN, Lptn, L-selectin, LT-a, LT-b, LTB4, LTBP-1, lung surface, luteinizing hormone, lymphotoxin β receptor, Mac-1, MAdCAM, MAG, MAP2, MARC, MCAM, MCK-2, MCP, M-CSF, MDC, Mer, METALLOPROTEASES, MGDF receptor, MGMT, MHC (HLA-DR), MIF, MIG, MIP, MIP-1-α, MK, MMAC1, MMP, MMP-1, MMP-10, MMP-11, MMP-12, MMP-13, MMP-14, MMP-15, MMP-2, MMP-24, MMP-3, MMP-7, MMP-8, MMP-9, MPIF, Mpo, MSK, MSP, mucin (Muc1), MUC18, Mullerian inhibitory substance, Mug, MuSK, NAIP, NAP, NCAD, N-cadherin, NCA 90, NCAM, enkephalinase, neurotrophin-3, -4 or -6, neurturin, nerve growth factor (NGF), NGFR, NGF-β, nNOS, NO, NOS, Npn, NRG-3, NT, NTN, OB, OGG1, OPG, OPN, OSM, OX40L, OX40R, p150, p95, PADPr, parathyroid hormone, PARC, PARP, PBR, PBSF, PCAD, P-cadherin, PCNA, PDGF, PDK-1, PECAM, PEM, PF4, PGE, PGF, PGI2, PGJ2, PIN, PLA2, placental alkaline phosphatase (PLAP), PIGF, PLP, PP14, proinsulin, prosomatostatin, protein C, PS, PSA, PSCA, prostate-specific membrane antigen (PSMA), PTEN, PTHrp, Ptk, PTN, R51, RANK, RANKL, RANTES, somatostatin A chain, somatostatin B chain, renin, respiratory syncytial virus (RSV) F, RSV Fgp, Ret, rheumatoid factor, RLIP76, RPA2, RSK, S100, SCF / KL, SDF-1, serine, serum albumin, sFRP-3, Shh, SIGIRR, SK-1, SLAM, SLPI, SMAC, SMDF, SMOH, SOD, SPARC, Stat, STEAP, STEAP-II, TACE, TACI, TAG-72(Tumor-associated glycoprotein-72), TARC, TCA-3, T-cell receptor (e.g., T-cell receptor α / β), TdT, TECK, TEM1, TEM5, TEM7, TEM8, TERT, testicular-like PLAP alkaline phosphatase, TfR, TGF, TGF-α, TGF-β, TGF-β Pan specificity, TGF-βRI (ALK-5), TGF-βRII, TGF-βRIIb, TGF-βRIII, TGF-β1, TGF-β2, TGF-β3, TGF-β4, TGF-β5, Thrombin, thymic Ck-1, thyroid-stimulating hormone, Tie, TIMP, TIQ, Tissue factor, TMEFF2, Tmpo, TMPRSS2, TNF, TNF-α, TNF-αβ, TNF-β2, TNFc, TNF-RI, TNF-RII, TNFRSF10A (TRAIL R1 Apo-2, DR4), TNFRSF10B (TRAIL R2 DR5, KILLER, TRICK-2A, TRICK-B), TNFRSF10C (TRAIL R3 DcR1, LIT, TRID), TNFRSF10D (TRAIL R4 DcR2, TRUNDD), TNFRSF11A (RANK ODF R, TRANCE R), TNFRSF11B (OPG OCIF, TR1), TNFRSF12 (TWEAK R FN14), TNFRSF13B (TACI), TNFRSF13C (BAFF R), TNFRSF14 (HVEM ATAR, HveA, LIGHT R, TR2), TNFRSF16 (NGFR p75NTR), TNFRSF17 (BCMA), TNFRSF18 (GITR AITR), TNFRSF19 (TROY TAJ, TRADE), TNFRSF19L (RELT), TNFRSF1A (TNF RI CD120a, p55-60), TNFRSF1B (TNF RII CD120b, p75-80), TNFRSF26 (TNFRH3), TNFRSF3 (LTbR TNF RIII, TNFC R), TNFRSF4 (OX40 ACT35, TXGP1 R), TNFRSF5 (CD40 p50), TNFRSF6 (Fas Apo-1, APT1, CD95), TNFRSF6B (DcR3 M68, TR6), TNFRSF7 (CD27), TNFRSF8 (CD30), TNFRSF9 (4-1BB CD137, ILA), TNFRSF21(DR6), TNFRSF22 (DcTRAIL R2 TNFRH2), TNFRST23 (DcTRAIL R1 TNFRH1), TNFRSF25 (DR3 Apo-3, LARD, TR-3, TRAMP, WSL-1), TNFSF10 (TRAIL Apo-2 ligand, TL2), TNFSF11 (TRANCE / RANK ligand ODF, OPG ligand), TNFSF12 (TWEAK Apo-3 ligand, DR3 ligand), TNFSF13 (APRIL TALL2), TNFSF13B (BAFF BLYS, TALL1, THANK, TNFSF20), TNFSF14 (LIGHT HVEM ligand, LTg), TNFSF15 (TL1A / VEGI), TNFSF18 (GITR ligand AITR ligand, TL6), TNFSF1A (TNF-a Conectin, DIF, TNFSF2), TNFSF1B (TNF-b LTa, TNFSF1), TNFSF3 (LTb TNFC, p33), TNFSF4 (OX4 ligand, gp34, TXGP1), TNFSF5 (CD40 ligand CD154, gp39, HIGM1, IMD3, TRAP), TNFSF6 (Fas ligand Apo-1 ligand, APT1 ligand), TNFSF7 (CD27 ligand CD70), TNFSF8 (CD30 ligand CD153), TNFSF9 (4-1BB ligand CD137 ligand), TP-1, t-PA, Tpo, TRAIL, TRAIL R, TRAIL-R1, TRAIL-R2, TRANCE, transferrin receptor, TRF, Trk, TROP-2, TSG, TSLP, tumor-associated antigen CA125, tumor-associated antigen expressing Lewis-Y related carbohydrate, TWEAK, TXB2, Ung, uPAR, uPAR-1, urokinase, VCAM, VCAM-1, VECAD, VE-cadherin, VE-cadherin-2, VEFGR-1 (flt-1), VEGF, VEGFR, VEGFR-3 (flt-4), VEGI, VIM, virus antigen, VLA, VLA-1, VLA-4, VNR integrin, von Willebrand disease (vonvon Willebrand factor, WIF-1, WNT1, WNT2, WNT2B / 13, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B, WNT10A, WNT10B, WNT11, WNT16, XCL1, XCL2, XCR1, XCR1, XEDAR, XIAP, XPD, HMGB1, IgA, Aβ, CD81, CD97, CD98, DDR1, DKK1, EREG, Hsp90, IL-17 / IL-17R, IL-20 / IL-20R, oxidized LDL, PCSK9, prekallikrein, RON, TMEM16F, SOD1, chromogranin A, chromogranin B, tau, VAP1, high molecular weight kininogen, IL-31, IL-31R, Nav1.1, Nav1.2, Nav1.3, Nav1.4, Nav1.5, Nav1.6, Nav1.7, Nav1.8, Nav1.9, EPCR, C1, C1q, C1r, C1s, C2, C2a, C2b, C3, C3a, C3b, C4, C4a, C4b, C5, C5a, C5b, C6, C7, C8, C9, factor B, factor D, factor H, properdin, sclerostin, fibrinogen, fibrin, prothrombinase, thrombin, tissue factor, factor V, factor Va, factor VII, factor VIIa, factor VIII, factor VIIIa, factor IX, factor IXa, factor X, factor Xa, factor XI, factor XIa, factor XII, factor XIIa, factor XIII, factor XIIIa, TFPI, antithrombin III, EPCR, thrombomodulin, TAPI, tPA, plasminogen, plasmin, PAI-1, PAI-2, GPC3, Syndecan-1, Syndecan-2, Syndecan-3, Syndecan-4, LPA and S1P; and receptors for hormones and growth factors. As discussed herein, in the amino acid sequence constituting the variable region, modification of one or more amino acid residues is permissible as long as their antigen-binding activity can be maintained. When modifying the amino acid sequence of the variable region, the position of the modification and the number of modified amino acids are not particularly limited. For example, the amino acids present in the CDR and / or FR can be appropriately modified. When the modified amino acids are in the variable region, it is preferably to maintain the binding activity and not particularly limited; for example, compared with before the modification, the binding activity can be 50% or greater, 80% or greater, and 100% or greater. In addition, the binding activity can be increased by amino acid modification. For example, the binding activity can be 2, 5, 10 times higher than before the modification, etc. The modification of the amino acid sequence can be at least any one of amino acid residue substitution, addition, deletion, and modification. For example, it is well-known to those of ordinary skill in the art to modify glutamine at the N-terminus of the variable region to pyroglutamic acid by pyroglutamylation. Therefore, when the N-terminus of the heavy chain is glutamine, the antibodies described herein may include variable regions in which glutamine is modified to pyroglutamic acid. The antibody variable regions described herein can have any sequence, and they can be antibody variable regions from any source, such as mouse antibodies, rat antibodies, rabbit antibodies, goat antibodies, camel antibodies, humanized antibodies generated by humanizing these non-human antibodies, and human antibodies. In addition, these antibodies can have various amino acid substitutions introduced into their variable regions to improve their antigen binding, pharmacokinetics, stability, and immunogenicity. Due to their pH-dependence in antigen binding, the variable regions may be able to bind to the antigen repeatedly (WO 2009 / 125825). κ chains and λ chains are present in the constant region of the antibody light chain, and either one is acceptable. In addition, they can have some amino acid modifications, such as substitution, deletion, addition, and / or insertion. In addition, the polypeptides including the variant Fc region described herein can be linked to other proteins, such as bioactive peptides, to form Fc fusion proteins. Such fusion proteins can be polymers of at least two polypeptides including the variant Fc region. Examples of other proteins include receptors, adhesion molecules, ligands, and enzymes, but are not limited thereto. Examples of Fc fusion proteins include proteins in which the Fc region is fused to a receptor that binds to a target molecule, including TNFR-Fc fusion proteins, IL1R-Fc fusion proteins, VEGFR-Fc fusion proteins, and CTLA4-Fc fusion proteins (Economides et al., Nat. Med. 9(1):47-52 (2003); Dumont et al., BioDrugs. 20(3):151-60 (2006)). In addition, the fused protein can be other molecules with target binding activity, for example, scFvs (WO 2005 / 037989), single domain antibodies (WO 2004 / 058821; WO 2003 / 002609), antibody-like molecules (Davinder, Curr. Op. Biotech.17:653-658 (2006); Current Opinion in Biotechnology18:1-10 (2007); Nygren et al., Curr. Op. Struct. Biol.7:463-469 (1997); and Hoss. Protein Science15:14-27 (2006)) such as DARPins (WO 2002 / 020565), affibodies (WO 1995 / 001937), Avimers (WO 2004 / 044011; WO 2005 / 040229) and Adnectins (WO 2002 / 032925). In addition, antibodies and Fc fusion proteins can be multispecific and can bind to multiple types of target molecules or epitopes. B. Recombinant methods and compositions Antibodies can be generated using recombinant methods and compositions, for example, as described in US 4,816,567. In one embodiment, there is provided an isolated nucleic acid encoding an anti - myostatin antibody as described herein. In another embodiment, there is provided an isolated nucleic acid encoding a polypeptide comprising a variant Fc region or a parental Fc region as described herein. Such nucleic acids can encode an amino acid sequence comprising VL and / or an amino acid sequence comprising VH of an antibody (e.g., the light and / or heavy chains of an antibody). In yet another embodiment, there is provided one or more vectors (e.g., expression vectors) comprising such nucleic acids. In yet another embodiment, there is provided a host cell comprising such nucleic acids. In one embodiment, the host cell comprises (e.g., has been transformed with): (1) a vector comprising a nucleic acid encoding an amino acid sequence comprising VL of an antibody and an amino acid sequence comprising VH of an antibody, or (2) a first vector comprising a nucleic acid encoding an amino acid sequence comprising VL of an antibody and a second vector comprising a nucleic acid encoding an amino acid sequence comprising VH of an antibody. In one embodiment, the host cell is eukaryotic, e.g., Chinese hamster ovary (CHO) cells or lymphocytes (e.g., Y0, NS0, and Sp20 cells). In one embodiment, there is provided a method for preparing an anti - myostatin antibody, wherein the method comprises culturing a host cell as provided above comprising a nucleic acid encoding the antibody under conditions suitable for the expression of the antibody, and optionally recovering the antibody from the host cell (or the host cell culture medium). In another embodiment, there is provided a method for preparing a polypeptide comprising a variant Fc region or a parental Fc region, wherein the method comprises culturing a host cell comprising a nucleic acid encoding the polypeptide under conditions suitable for the expression of the polypeptide, the polypeptide being an antibody, Fc region, or variant Fc region as provided above, and optionally recovering the polypeptide from the host cell (or the host cell culture medium). For recombinant production of anti - myostatin antibodies, for example, the nucleic acids encoding the antibodies as described above are isolated and inserted into one or more vectors for further cloning and / or expression in a host cell. For recombinant production of Fc regions, the nucleic acids encoding the Fc regions are isolated and inserted into one or more vectors for further cloning and / or expression in a host cell. Such nucleic acids can be easily isolated and sequenced using conventional procedures (e.g., using oligonucleotide probes that can specifically bind to the genes encoding the heavy and light chains of the antibody). Suitable host cells for cloning or expression of vectors encoding antibodies include the prokaryotic or eukaryotic cells described herein. For example, antibodies can be produced in bacteria, particularly when glycosylation and Fc effector functions are not required. For expression of antibody fragments and polypeptides in bacteria, see, e.g., US 5,648,237, US 5,789,199, and US 5,840,523. (See also, Charlton, Methods in Molecular Biology, Vol. 248 (edited by B.K.C. Lo, Humana Press, Totowa, NJ, 2003), pp. 245-254, which describes the expression of antibody fragments in Escherichia coli). After expression, the antibody can be isolated from the bacterial cell paste of the soluble fraction and further purified. In addition to prokaryotes, eukaryotic microorganisms such as filamentous fungi or yeasts are suitable cloning or expression hosts for vectors encoding antibodies, including fungal and yeast strains whose glycosylation pathways have been "humanized", resulting in the production of antibodies with a partial or complete human glycosylation pattern. See Gerngross, Nat. Biotech. 22:1409-1414 (2004) and Li et al., Nat. Biotech. 24:210-215 (2006). Host cells suitable for the expression of glycosylated antibodies are also derived from multicellular organisms (invertebrates and vertebrates). Examples of invertebrate cells include plant and insect cells. A variety of baculovirus strains have been identified that can be used in conjunction with insect cells, particularly for the transfection of Spodoptera frugiperda cells. Plant cell cultures can also be used as hosts. See, for example, U.S. Patent Nos. 5,959,177, 6,040,498, 6,420,548, 7,125,978, and 6,417,429 (describing the PLANTIBODIES™ technology for producing antibodies in transgenic plants). Vertebrate cells can also be used as hosts. For example, mammalian cell lines adapted to grow in suspension can be used. Other examples of useful mammalian host cell lines are the simian kidney CV1 cell line transformed with SV40 (COS-7); the human embryonic kidney cell line (293 or, for example, 293 cells as described by Graham et al., J. Gen Virol. 36:59 (1977)); baby hamster kidney cells (BHK); mouse supporting cells (e.g., Mather, TM4 cells as described in Biol. Reprod. 23:243-251 (1980); monkey kidney cells (CV1); African green monkey kidney cells (VERO-76); human cervical cancer cells (HELA); dog kidney cells (MDCK); buffalo rat liver cells (BRL 3A); human lung cells (W138); human liver cells (Hep G2); mouse mammary tumor (MMT 060562); e.g., as Mather et al., TRI cells as described in Annals N.Y. Acad. Sci. 383:44-68 (1982); MRC 5 cells; and FS4 cells. Other useful mammalian host cell lines include Chinese hamster ovary (CHO) cells, which contain DHFR - CHO cells (Urlaub et al., Proc. Natl. Acad. Sci. USA 77:4216 (1980)); and myeloma cell lines such as Y0, NS0, and Sp2 / 0. A review of specific mammalian host cell lines suitable for antibody production can be found, e.g., in Yazaki and Wu, Methods in Molecular Biology, Vol. 248 (edited by B.K.C. Lo, Humana Press, Totowa, NJ), pp. 255-268 (2003). Antibodies with pH-dependent properties can be obtained, e.g., by screening methods and / or mutagenesis methods as described in WO 2009 / 125825. The screening method can include any procedure for identifying antibodies with pH-dependent binding properties in a population of antibodies specific for a particular antigen. In some specific embodiments, the screening method can include measuring one or more binding parameters (e.g., KD or kd) of a single antibody in the original population of antibodies at acidic and neutral pH. The measurement of the binding parameters of the antibody can utilize, e.g., surface plasmon resonance or any other analytical method capable of quantitatively or qualitatively evaluating the binding properties of the antibody to a particular antigen. In some specific embodiments, the screening method can include identifying antibodies that bind to the antigen with an acidic / neutral KD ratio of 2 or greater. In still other embodiments, the screening method can include identifying antibodies that bind to the antigen with a pH5.8 / pH7.4 KD ratio of 2 or greater. Alternatively, the screening method can include identifying antibodies that bind to the antigen with an acidic / neutral kd ratio of 2 or greater. In still other embodiments, the screening method can include identifying antibodies that bind to the antigen with a pH5.8 / pH7.4 kd ratio of 2 or greater. In another embodiment, the mutagenesis method may include introducing deletions, substitutions or additions of amino acids into the heavy and / or light chains of the antibody to enhance the pH-dependent binding of the antibody to the antigen. In some specific embodiments, mutagenesis may be carried out in one or more variable domains of the antibody, e.g., in one or more HVRs (e.g., CDRs). For example, the mutagenesis may include substituting an amino acid in one or more HVRs (e.g., CDRs) of the antibody with another amino acid. In some specific embodiments, the mutagenesis may include substituting one or more amino acids in at least one HVR (e.g., CDR) of the antibody with histidine. In some specific embodiments, "enhanced pH-dependent binding" means that the mutated form of the antibody exhibits a greater acidic / neutral KD ratio, or a greater acidic / neutral kd ratio, compared to the original "parental" (i.e., lower pH-dependent) form of the antibody prior to mutagenesis. In some specific embodiments, the mutated form of the antibody has an acidic / neutral KD ratio of 2 or greater. In some specific embodiments, the mutated form of the antibody has a pH5.8 / pH7.4 KD ratio of 2 or greater. Alternatively, the mutated form of the antibody has an acidic / neutral kd ratio of 2 or greater. In still other embodiments, the mutated form of the antibody has a pH5.8 / pH7.4 kd ratio of 2 or greater. Polyclonal antibodies are preferably produced by multiple subcutaneous (sc) or intraperitoneal (ip) injections of the relevant antigen and adjuvant into an animal. The use of bifunctional or derivatizing reagents (e.g., maleimidobenzoyl sulfosuccinimide ester (coupled via cysteine residues), N-hydroxysuccinimide (coupled via lysine residues), glutaraldehyde, succinic anhydride, SOCl 2, or R 1 N═C═NR, where R and R 1 are different alkyl groups) to couple the relevant antigen to a protein that is immunogenic in the species to be immunized (e.g., keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, or soybean trypsin inhibitor) is useful. Animals (usually non-human mammals) are immunized against an antigen, immunogenic conjugate or derivative by combining, for example, 100 μg or 5 μg of protein or conjugate (for rabbits and mice respectively) with three volumes of Freund's complete adjuvant and injecting the solution intradermally at multiple sites. One month later, the animals are boost-immunized with 1 / 5 to 1 / 10 of the original amount of the peptide or conjugate in Freund's complete adjuvant by subcutaneous injection at multiple sites. On days 7 - 14 after the boost injection, the animals are bled and the antibody titration concentration of the serum is determined. The animals are boost-immunized until titer plateaus are reached. Preferably, the animals are boost-immunized with conjugates of the same antigen but conjugated to different proteins and / or by different cross-linking agents. The conjugates can also be produced in recombinant cell cultures as protein fusions. Coagulants such as alum are also suitable for enhancing the immune response. Monoclonal antibodies can be obtained from a substantially homogeneous population of antibodies, i.e., a population in which individual antibodies are identical except for possible naturally occurring mutations and / or post-translational modifications (e.g., isomerization, amidation) that may be present in minor amounts. Thus, the modifier "monoclonal" indicates the character of the antibody and it is not a mixture of discrete antibodies. For example, monoclonal antibodies can be formed by the hybridoma method first described by Kohler et al., Nature 256(5517):495 - 497 (1975). In the hybridoma method, a mouse or other suitable host animal, such as a hamster, is immunized as described herein to induce lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing protein. Alternatively, the lymphocytes can be immunized in vitro. The immunizing agent will usually comprise a protein of the antigen or a fusion variant thereof. Generally, peripheral blood lymphocytes (PBL) are used if cells of human origin are desired, or spleen cells or lymph node cells are used if cells of non-human mammalian origin are desired. The lymphocytes are then fused with an immortal cell line using a suitable fusing agent, such as polyethylene glycol, to form hybridoma cells (Goding, Monoclonal Antibodies: Principles and Practice, Academic Press (1986), pp. 59 - 103). Immortalized cell lines are generally transformed mammalian cells, particularly myeloma cells of rodent, bovine, and human origin. Usually, myeloma cell lines from rats or mice are used. The hybridoma cells thus prepared are inoculated and grown in a suitable medium, which preferably contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells. For example, if the parental myeloma cells lack hypoxanthine-guanine phosphoribosyl transferase (HGPRT or HPRT), the medium for the hybridoma will usually contain hypoxanthine, aminopterin, and thymidine (HAT medium), which prevent the growth of HGPRT-deficient cells. Preferred immortal myeloma cells are those that fuse efficiently, support stable high-level production of antibodies by the selected antibody-producing cells, and are sensitive to media such as HAT medium. Among these, preferred are mouse myeloma lines such as those obtained from MOPC-21 and MPC-11 mouse tumors, available from the Salk Institute Cell Distribution Center, San Diego, California, USA, and the SP-2 cells (and its derivatives such as X-63-Ag8-653) available from the American Type Culture Collection, Manassas, Virginia, USA. Human myeloma and mouse-human hybrid myeloma cell lines have also been described for the production of human monoclonal antibodies (Kozbor et al., J Immunol. 133(6):3001-3005 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications; Marcel Dekker, Inc., New York, pp. 51-63 (1987)). Determine whether monoclonal antibodies against the antigen are produced in the medium in which the hybridoma cells are grown. Preferably, the binding specificity of the monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay (e.g., radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA)). Such techniques and assays are well known in the art. The binding affinity can be determined by the Scatchard analysis of Munson, Anal Biochem. 107(1):220-239 (1980). After hybridoma cells with the desired specificity, affinity and / or activity are identified, these clones can be subcloned by limiting dilution procedures and growth using standard methods (Goding, supra). Media suitable for this purpose include, for example, D-MEM or RPMI-1640 medium. In addition, hybridoma cells can be grown in vivo as tumors in mammals. The monoclonal antibodies secreted by the subclones are appropriately isolated from the culture medium, ascites fluid or serum by conventional immunoglobulin purification procedures such as, for example, protein A-agarose, hydroxyapatite chromatography, gel electrophoresis, dialysis or affinity chromatography. Antibodies can be generated by immunizing a suitable host animal against an antigen. In one embodiment, the antigen is a polypeptide comprising full-length myostatin. In one embodiment, the antigen is a polypeptide comprising latent myostatin. In one embodiment...

Claims

1. A polypeptide comprising a variant Fc region, comprising at least two amino acid modifications in a parental Fc region, wherein the parental Fc region is derived from human IgG1, wherein the variant Fc region comprises Q311R and P343R substitutions, which, according to EU designations, increase the isoelectric point (pI) of the variant Fc region compared to the parental Fc region.

2. The polypeptide as claimed in claim 1, wherein the amino acid modifications are exposed on the surface of the variant Fc region.

3. The polypeptide as described in claim 1 further includes an antigen-binding domain.

4. The polypeptide as claimed in claim 3, wherein the antigen-binding activity of the antigen-binding domain varies depending on ion concentration conditions.

5. The polypeptide as claimed in any one of claims 1 to 4, wherein the polypeptide is an antibody or an Fc fusion protein.

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